505 Penobscot Dr.

Redwood City, California 94063

April 28, 2020

Dear Guardant Stockholder:

We are cordially invitedpleased to invite you to attend the Guardant Health, Inc. 20202022 Annual Meeting of Stockholders (the “Annual Meeting”) to be held on Friday,Wednesday, June 12, 2020,15, 2022, at 9:30 a.m., Pacific Time. In lightTime, virtually at www.virtualshareholdermeeting.com/GH2022.

Without a doubt, 2021 was a remarkable year for Guardant Health as we continue to lead the way in creating blood tests that help patients across all stages of the coronavirus/COVID-19 outbreakcancer live longer and in the best interestshealthier lives. Last year, we launched three new products that are transforming cancer care including Guardant360 Response^™ for treatment selection, Guardant Reveal^™ for residual disease detection and recurrence monitoring, and Guardant 360 Tissue Next^™ for when a tissue biopsy is needed. The U.S. Food and Drug Administration also granted regulatory approval of public healthGuardant360® CDx as a companion diagnostic to identify non-small cell lung cancer (“NSCLC”) patients who may benefit from treatment with RYBREVANT^™ (amivantamab-vmjw) and the health and safety of our Board of Directors, employees and stockholders,LUMAKRAS^™ (sotorasib). Earlier this year, the Annual MeetingJapanese Ministry of Health, Labour and Welfare granted regulatory approval of Guardant360® CDx in patients with advanced solid tumors and as a companion diagnostic to identify colorectal cancer patients who may benefit from treatment with Opdivo® (nivolumab) and NSCLC patients who may benefit from treatment with LUMAKRAS^™ (sotorasib).

In addition to expanding our oncology portfolio, we continue to make great progress across our screening program. In 2022, Guardant Health will be held completely virtually vialaunch Guardant Shield^™ LDT, the company’s first blood-based screening test to detect colorectal cancer, where today one in three adults is not getting the recommended screening. This test is also being studied in a large registrational trial to support its use in screening for lung cancer. With the launch of our first blood-based screening test in 2022, Guardant Health will become the first company to have offerings across the whole continuum of cancer care.

We also expanded our biopharma business, ending the year with over 100 partnerships to help bring the next generation of cancer therapeutics to patients sooner. In addition, we continued to expand our footprint internationally. In 2021, we announced that we are building two labs to expand our global laboratory network, one in Spain with Vall d’Hebron and other at The Royal Marsden in the UK.

As we embark on our ten-year anniversary, Guardant Health is well positioned to build on our expertise of bringing innovative products to market that help patients across all stages of cancer live interactive audio webcast onlonger and healthier lives. In recognition of our company’s evolution these past ten years, we have engaged in a company-wide introspective exercise of determining how our values have also evolved, never losing sight that each day starts and ends with putting the Internet. You will be ablepatient first. We want to attend, votethank our employees for their relentless commitment and submithard work to bring this purpose to life. We also want to thank our business partners, healthcare providers, patients, the cancer community and our stockholders for your questions on line during the Annual Meeting at www.virtualshareholdermeeting.com/GH2020. You will not be ablecontinued support and confidence in our efforts to attend the Annual Meeting in person.transform cancer care.

Sincerely,

Helmy Eltoukhy

Chairperson and voted at the Annual Meeting. You may vote on the Internet or by telephone as instructed in the Notice of Internet Availability of Proxy Materials or, if you are receiving a paper copy of the proxy materials, you may complete, sign and date the enclosed proxy card and return it in the enclosed envelope as soon as possible. This action will not prevent you from voting your shares online at www.virtualshareholdermeeting.com/GH2020 on the day of the Annual Meeting if you subsequently choose to attend the Annual Meeting via audio webcast.

AmirAli Talasaz

Co-Chief Executive Officer

505 Penobscot Dr.

Redwood City, California 94063

NOTICE OF 20202022 ANNUAL MEETING OF STOCKHOLDERS

TO BE HELD ON JUNE 12, 2020

To the Stockholders of Guardant Health, Inc.:

These matters are more fully described in our proxy materials accompanying this Notice.

We know of no other matters to come before the Annual Meeting. Only stockholders who owned shares of record of our common stock of Guardant Health, Inc. at the close of business on April 20, 2020,18, 2022 are entitled to notice of and to vote on matters brought for vote at the Annual Meeting or at any postponements or adjournments thereof.

General

Your proxy is solicited on behalf of the Board of Directors (the “Board”) of Guardant Health, Inc., a Delaware corporation (as used herein, “Guardant,” ”Guardant Health,” “we,” “us” or “our”), for use at our 20202022 annual meeting of stockholders (the “Annual Meeting”) to be held on Friday,Wednesday, June 12, 2020,15, 2022, at 9:30 a.m. Pacific Time, virtually at www.virtualshareholdermeeting.com/GH2020,www. virtualshareholdermeeting.com/GH2022, or at any continuation, postponement or adjournment thereof, for the purposes discussed in this proxy statement and in the accompanying Notice of Annual Meeting and any other business properly brought before the Annual Meeting. Proxies are solicited to give all stockholders of record an opportunity to vote on matters properly presented at the Annual Meeting.

Virtual Annual Meeting.Meeting. The Annual Meeting will be a virtual meeting of stockholders using cutting-edge technology, conducted via live audio webcast. You are invited to attend the Annual Meeting online. We believe that a virtual meeting will provideprovides expanded stockholder access and participation, improved communications, as well as additional safeguards for healthy and safety in light of developments related to COVID-19.improved communications. You will be able to attend, vote and submit your questions on lineonline during the Annual Meeting. You will not be able to attend the Annual Meeting in person. Stockholders may attend the Annual Meeting online at www.virtualshareholdermeeting.com/GH2020 by logging into www. virtualshareholdermeeting.com/GH2022 using the 16-digit control number included on your Notice of Internet Availability of Proxy Materials, on your proxy card, or on the voting instruction form provided by your broker, bank or other nominee.

Notice and Access Proxy Delivery. Delivery. We have elected to provide access to our proxy materials over the Internet. Accordingly, we are sending a Notice of Internet Availability of Proxy Materials (the “Notice”) to most of our stockholders of record, and paper copies of the proxy materials to certain other stockholders of record. Brokers and other nominees who hold shares on behalf of beneficial owners will be sending their own similar Notice.Notice to such beneficial owners. All stockholders will have the ability to access the proxy materials on the website referred to in the Notice or request to receive a printed set of the proxy materials. You can find instructions on how to request a printed copy by mail or electronically on the Notice and on the website referred to in the Notice, including an option to request paper copies on an ongoing basis. On or about April 28, 2020,2022, we intend to make this proxy statement available on the Internet and to commence mailing of the Notice to all stockholders entitled to vote at the Annual Meeting. We intend to mail this proxy statement, together with a proxy card, to those stockholders entitled to vote at the Annual Meeting who have properly requestedrequest paper copies of such materials, within three business days of such request.

Our proxy statement and 20192021 Annual Report are available at www.proxyvote.com. This website address contains: the Notice of Annual Meeting, the proxy statement and proxy card sample, and the 20192021 Annual Report. You will need your 16-digit control number that is included on your Notice, on your proxy card, or on the voting instruction form provided by your

Record holders of our common stock as of the close of business on April 20, 2020,18, 2022, the record date for the Annual Meeting (the “Record Date”), are entitled to notice of and to vote at the Annual Meeting on all matters to be voted upon. As of the Record Date, there were 94,543,441101,919,898 shares of our common stock outstanding. On each matter presented to our stockholders for vote, the holders of common stock are entitled to one vote per share held as of the Record Date.

The method of voting by proxy differs (1) depending on whether you are viewing this proxy statement on the Internet or receiving a paper copy and (2) for shares held as a record holder and shares held in “street name.”

Record Holder. Holder. If you hold your shares of common stock as a record holder and you are viewing this proxy statement on the Internet, you may vote by submitting a proxy over the Internet by following the instructions on the website referred to in the Notice previously mailed to you. If you hold your shares of common stock as a record holder and you are reviewing a paper copy of this proxy statement, you may vote your shares by completing, dating and signing the proxy card that was included with the proxy statement and promptly returning it in the preaddressed, postage paid envelope provided to you, or by submitting a proxy over the Internet or by telephone by following the instructions on the proxy card.

Hold in Street Name. Name. If you hold your shares of common stock in street name, which means your shares are held of record by a broker, bank or nominee, you will receive a Notice from your broker, bank or other nominee that includes instructions on how to vote your shares. Your broker, bank or nominee will allow you to deliver your voting instructions over the Internet and may also permit you to vote by telephone. In addition, you may request paper copies of the proxy statement and proxy card from your broker by following the instructions on the Notice provided by your brokerbroker.

General.

Voting at the Virtual Annual Meeting. Meeting. To attend and vote at the Annual Meeting you need to access the meeting via live audio webcast at www.virtualshareholdermeeting.com/GH2020GH2022 using the 16-digit control number included on your Notice, on your proxy card or on the voting instruction form. Attendance at the Annual Meeting will not, by itself, result in any vote or revocation of a prior vote. You must follow the instructions at www.virtualshareholdermeeting.com/GH2020www.virtualshareholdermeeting. com/GH2022 to vote your shares at the Annual Meeting.

All shares entitled to vote and represented by properly submitted proxies (including those submitted electronically, telephonically and in writing) received before the polls are closed at the Annual Meeting, and not revoked or superseded, will be voted at the Annual Meeting in

The proxy gives each of Helmy Eltoukhy, AmirAli Talasaz and Michael WileyJohn Saia discretionary authority to vote your shares in accordance with their best judgment with respect to all additional matters that might come before the Annual Meeting.

If you receive more than one proxy card or Notice, it means you hold shares that are registered in more than one account. To ensure that all of your shares are voted, sign and return each proxy card or, if you submit a proxy by telephone or the Internet, submit one proxy for each proxy card or Notice you receive.

If your shares are held of record, you may change or revoke your proxy at any time before your proxy is voted at the Annual Meeting by taking any of the following actions:

Written notices of revocation and other communications with respect to the revocation of Company proxies by record holders should be addressed to:

Brokers, banks or other nominees who hold shares of common stock in “street name” for a beneficial owner of those shares typically have the authority to vote in their discretion on “routine” proposals when they have not received instructions on how to vote on such matter from beneficial owners. However, brokers are not allowed to exercise their voting discretion with respect to the election of directors or for the approval of matters that are considered “non-routine”“non-routine” without specific voting instructions from the beneficial owner. These non-votedIf you hold your shares are referredin street name and do not provide voting instructions to asyour broker on how to vote on the election of directors or other “non-routine” proposals, your broker cannot exercise discretion to vote you shares and your shares will be considered to be “broker non-votes.” Ifnon-votes” and will not be voted on such matters. Accordingly, if your broker holds your common stock in “street name,” your broker will vote your shares on “non-routine”the election of directors and other “non-routine” proposals only if you provide instructions to your broker on how to vote your shares by following the procedures outlined in the voting instruction form sent to you by your broker. Only Proposal No. 2 (ratifying the appointment of our independent registered public accounting firm) is considered a routine matter on which your broker may vote without instruction from you as the beneficial owner. Proposal No. 1 (election of directors) and Proposal No. 3 (determining the frequency of stockholder advisory say-on-pay votes),(advisory vote to approve named executive officer compensation) are considered non-routine matters, and without your instruction, your broker cannot vote your shares for either of Proposal No. 1 or Proposal No. 3.

The inspector of elections appointed for the Annual Meeting will tabulate votes cast by proxy, telephone and via Internet at www.proxyvote.com as of 11:59 p.m. EDT on June 11, 202014, 2022 and at www.virtualshareholdermeeting.com/GH2020 on the day of andGH2022 during the Annual Meeting. The inspector of elections will also determine whether a quorum is present. In order to constitute a quorum for the conduct of business at the Annual Meeting, the holders of a majority of the shares of common stock issued and outstanding and entitled to vote at the Annual Meeting must be present or represented by proxy at the Annual Meeting. On the Record Date, there were 101,919,898 shares of common stock entitled to vote at the Annual Meeting. Shares that abstain from voting on any proposal, or that are represented by broker non-votes, will be treated as shares that are present and entitled to vote at the Annual Meeting for purposes of determining whether a quorum is present.

Proposal No. 2: Ratification of Independent Registered Public Accounting Firm.Firm. The affirmative vote of the holders of a majority of the votes cast at the Annual Meeting is required for the ratification of the selectionappointment of Ernst & Young LLP as our independent registered public accounting firm. Thus, the number of votes “FOR” must exceed the number of votes “AGAINST.” Abstentions are considered to be votes not cast on this proposal and thus will have no effect. Brokers generally have discretionary authority to vote on the ratification of our independent registered public accounting firm, thus broker non-votes are not expected to result from the vote on Proposal No. 2. Any broker non-votes would be considered votes not cast and thus would have no effect.

Proposal No. 3: Determine the Frequency of Stockholder Advisory Say-on-Pay VotesVote to Approve Named Executive Officer Compensation. The affirmative vote of the holders of a majority of the votes cast at the Annual Meeting is required for determining approval on an advisory basis of the frequencycompensation of stockholder advisory say-on-pay votes.our named executive officers, as described in the “Compensation Discussion and Analysis,” executive compensation tables and accompanying narrative disclosures in our proxy materials. Abstentions and brokernon-votes

In their discretion, the proxy holders named in the proxy are authorized to vote on any other matters that may properly come before the Annual Meeting and at any continuation, postponement or adjournment thereof. The Board knows of no other items of business that will be presented for consideration at the Annual Meeting other than those described in this proxy statement. In addition, no stockholder proposal or nomination was received on a timely basis, so no such matters may be brought to a vote at the Annual Meeting.

The live audio webcast of the Annual Meeting will begin promptly at 9:30 a.m. Pacific Time. Online access to the audit webcast will open approximately 15 minutes prior to the start of the Annual Meeting to allow time for our stockholders to log in and test their devices’ audio system. We encourage our stockholders to access the meeting in advance of the designated start time.

Instructions on how to connect to the Annual Meeting, participate and demonstrate proof of stock ownership are posted on www.virtualshareholdermeeting.com/GH2020.GH2022. To participate in the Annual Meeting, you will need to log-in using the 16-digit control number on your Notice, proxy card or voting instruction form.

Beginning 15 minutes prior to the start of and during the Annual Meeting, we will have a support team ready to assist stockholders with any technical difficulties they may have accessing or hearing the virtual meeting. If you encounter any difficulties accessing the virtual meeting during the check-in or meeting time, you shouldplease call ourthe technical support team at (800) 586-1548 (US Domestic Toll Free) or (303) 562-9288 (International).

Stockholders may submit questions and vote during the Annual Meeting on www.virtualshareholdermeeting.com/GH2020.www. virtualshareholdermeeting.com/GH2022. You will need to enter the 16-digit control number received with your Notice, proxy card or voting instruction form as proof of stock ownership in order to be able to submit questions and vote at our Annual Meeting. After the business portion

Our Board is soliciting proxies for the Annual Meeting from our stockholders. We will bear the entire cost of soliciting proxies from our stockholders. In addition to the solicitation of proxies by delivery of the Notice or proxy statement by mail, we will request that brokers,

A list of stockholders eligible to vote at the Annual Meeting will be available for inspection, for any purpose germane to the Annual Meeting, at our corporate headquarters for a period of no less than ten days prior to the Annual Meeting. Please contact our Corporate Secretary at CorpSecretary@guardanthealth.com if you are interested in viewing the list. The list of stockholders will also be made available on www.virtualshareholdermeeting.com/GH2020GH2022 during the Annual Meeting.

The Governance Committee is mindful of the policies regarding board service of certain investors and proxy advisory firms, which policies were developed due to concerns that “overboarded” directors face excessive time commitments and challenges in fulfilling their duties. Mr. Clark and Dr. Jallal may be deemed “overboarded” under certain policies. The Governance Committee reviewed and considered the contributions of Mr. Clark and Dr. Jallal to the Board and noted their strong attendance, preparedness and engagement at Board and committee meetings. The Governance Committee also noted Mr. Clark’s valuable and extensive public company director experience and expertise and Dr. Jallal’s extensive experience in the biopharmaceutical industry, in particular, her expertise in drug development and commercialization across global markets.

The Governance Committee will consider stockholder recommendations of candidates on the same basis as it considers all other candidates. Stockholders may propose director nominees by adhering to the advance notice procedures described in the section entitled “Other Matters-StockholderMatters: Stockholder Proposals and Nominations” in this proxy statement and must include all information as required under our Amended and Restated Certificate of Incorporation (the “Certificate of Incorporation”) and Amended and Restated Bylaws (the “Bylaws”), and any other information that would be required to solicit a proxy under federal securities law.laws. We may request from the recommending stockholder or recommending stockholder group such other

Our Governance Committee and our Board have undertaken a review of the Board’s composition, the composition of Board committees and the independence of each director. Based upon information concerning each director’s background, employment and affiliations, including family relationships, the Board has affirmatively determined that each of Messrs.Ian Clark, Meresman,Vijaya Gadde, Bahija Jallal, Meghan Joyce, Samir Kaul, and Nishar, and Dr. Jallal,Myrtle Potter is independent, as defined under the applicable listing requirements and rules of the Nasdaq and theGlobal Select Market (“Nasdaq”) and the Securities and Exchange Commission (the “SEC”), and that each of them and their respective family members have no material relationship with us, commercial or otherwise, that would interfere with the exercise of their independent judgment in carrying out the responsibilities of a director. In addition, the Board affirmatively determined that Stanley Meresman, who served as a Class I director with a term expiring at the Annual Meeting and who is not standing for re-election, was an independent director under the listing requirements and rules of the Nasdaq and SEC, and that neither he nor his family members had a relationship with us that interfered with his independent judgment in carrying out the responsibilities of a director. Drs. Eltoukhy and Talasaz were determined to not be not independent due to their service as our Chief Executive Officer (“CEO”), and as our President and Chief Operating Officer (“COO”), respectively.Co-CEOs. In making these determinations, the Board considered the current and prior relationships that each non-employee director has with us and all other facts and circumstances the Board deemed relevant in determining their independence, including the beneficial ownership of our capital stock by each non-employee director.

Our Board has determined that at this time it is in the best interests of the Company and our stockholders to have AmirAli Talasaz,Helmy Eltoukhy, our President and COO,Co-CEO, serve as our ChairmanChairperson of the Board, coupled with a strong lead independent director. Dr. Eltoukhy was appointed as Chairperson of the Board on August 5, 2021, succeeding AmirAli Talasaz in this role. We believe having one of our founderssenior executives serve as ChairmanChairperson promotes responsibility and accountability, and that our Board benefits from having a ChairmanChairperson with his extensive understanding of our business and the unique challenges we face. The Board believes that this structure best facilitates consistent leadership direction

Our Board also recognizes the value and importance of a strong independent lead director with clearly delineated responsibilities. The independent directors have appointed Ian Clark to serve as our lead independent director.

As set forth in our Corporate Governance Guidelines, Mr. Clark, as our independent lead director, has clearly delineated and comprehensive duties, including:

Compensation Committee

Each of our committees periodically provide updates to the Board regarding significant risk management issues and management’s response.

Any interested person, including any stockholder, may communicate with our Board by written mail addressed to Guardant Health, Inc. Board of Directors, c/o Corporate Secretary,

ELECTION OF DIRECTORS

Pursuant to our Certificate of Incorporation and our Bylaws, the total number of directors constituting the Board is fixed from time to time by the Board. There are currently sevennine authorized directors and nine persons serving as directors. EffectiveThe Board has reduced the authorized number of directors effective as of the Annual Meeting the board has set the authorized number of directors at six. Dr. Bahija Jallal was appointed to our Board as a Class III Director effective April 17, 2019. Aaref Hilaly resigned from our Board effective November 6, 2019. Dipchand Nishar notified us that he will not be standing for re-election to the Board at the Annual Meeting due to his increased responsibilities with respect to the SoftBank Vision Fund portfolio companies in light of the COVID-19 pandemic.

The Board and the Governance Committee believe the skills, qualities, attributes and experience of our directors provide us with business acumen and a diverse range of perspectives to engage each other and management to effectively address effectively our evolving needs and represent the best interests of our stockholders.

Vacancies on the Board, including any vacancy created by an increase in the size of the Board, may be filled only by a majority of the directors remaining in office, even though less than a quorum of the Board, or a sole remaining director. A director elected by the Board to fill a vacancy will serve until the next election of the class of directors for which such director was chosen and until such director’s successor is elected and qualified, or until such director’s earlier retirement, resignation, disqualification, removal or death.

If any nominee should become unavailable for election prior to the Annual Meeting, an event that currently is not anticipated by the Board, the proxies will be voted in favor of the election of a substitute nominee or nominees proposed by the Board or the number of directors may be reduced accordingly. Each nominee has agreed to serve if elected and the Board has no reason to believe that any nominee will be unable to serve.

Set forth below is biographical information for each nominee and a summary of the specific qualifications, attributes, skills and experiences which led the Board to conclude that each nominee should serve on the Board at this time. In order to better understand the biographical information set forth below, please note that Guardant Health, Inc. was formed in December 2011 and our initial public offering closed in October 2018.

Directors who will continue to serve after the Annual Meeting are listed below.

The following sets for the biographical information of our Executive Officers. Biographical information pertaining to Helmy Eltoukhy, who is a memberour Chairperson of ourthe Board and our CEO,Co-CEO, and AmirAli Talasaz, who is the Chairmana member of ourthe Board and our President and COO,Co-CEO, may be found in the section above entitled “Proposal 1: Election of Directors-InformationDirectors – Information about Other Directors Not Standing for Election at this Meeting.”

We are a leading precision oncology company focused on helping to conquer cancer globally through the use of our proprietary blood-based tests, vast data sets and advanced analytics. Today our proprietary tests are helping to realize the full potential of precision oncology by providing patients and their doctors critical insights that can inform decisions at all stages of the disease, from screening, to monitoring cancer recurrence, to treatment decisions. We believe that the key to conquering cancer is unprecedented access to its molecular information throughout all stages of the disease, which we intend to enable by our tests. By looking at the

We had ananother exceptionally strong year in 2019,2021, notwithstanding the continued impact of COVID-19, with outstanding growth in our financial results and superbstrong progress in our

Financial Results

Gross profit is calculated as total revenue less costs of precision oncology testing and costs of development services.services and other. Gross margin is calculated as gross profit divided by total revenue.

The Financial Performance Component was comprised of of:

(i) a revenue goal, which represented 50%40% of the target bonus opportunity, and

(ii) adjusted EBITDA and gross margin and operating income (loss) goals, each of which represented 15% and 5%, respectively, of the target bonus opportunity.

The Compensation Committee set a rigorous revenue target substantially above the prior-year level, reflecting 49%32% growth. In addition, there was rigor in the performance curve, as the threshold level40% of target bonus attributed to revenue performance was setwould be forfeited if we didn’t achieve at 85% of the target (i.e., 27%least 18% growth from 2018 actual revenue achievement).the prior year. The targets for gross margin and operating income (loss)adjusted EBITDA were also set at levels that the Compensation Committee viewed as challenging to achieve. The Compensation Committee incorporated these measures in order to focus executive officers on the critical strategic priorities of top line revenue growth and operating profitability.

The Operational Performance Component targets were also demanding and included two new product launches and three Guardant SHIELD clinical trial program goals, representing a regulatory objective, the filing of a PMA with the U.S. Food and Drug Administration for one of our tests for use as a companion diagnostic, representing 20%combined 40% of the target bonus opportunity, and research and development pipeline objectives, including certification of our LUNAR-1 assay under the standard for clinical laboratories, and the enrollment of patients in a trial of the LUNAR-1 assay, representing 20% of the target bonus opportunity.

The Compensation Committee assesses the effectiveness of our executive compensation program from time to time and reviewreviews risk mitigation and governance matters, which includes maintaining the following best practices: