<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2020-06-18</periodOfReport>

    <noSecuritiesOwned>0</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001580063</issuerCik>
        <issuerName>PROGENITY, INC.</issuerName>
        <issuerTradingSymbol>PROG</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001813865</rptOwnerCik>
            <rptOwnerName>Gianakopoulos George</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O PROGENITY, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>4330 LA JOLLA VILLAGE DRIVE, SUITE 200</rptOwnerStreet2>
            <rptOwnerCity>SAN DIEGO</rptOwnerCity>
            <rptOwnerState>CA</rptOwnerState>
            <rptOwnerZipCode>92122</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>1</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle>Senior Vice President of Sales</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <nonDerivativeTable>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>23499</value>
                    <footnoteId id="F1"/>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>6.49</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <value>2024-09-22</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>13759</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>10.75</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F3"/>
            </exerciseDate>
            <expirationDate>
                <value>2025-02-01</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>4046</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>12.54</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F4"/>
            </exerciseDate>
            <expirationDate>
                <value>2026-02-24</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>4855</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>9.88</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F5"/>
            </exerciseDate>
            <expirationDate>
                <value>2027-02-23</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>6474</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>9.88</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F6"/>
            </exerciseDate>
            <expirationDate>
                <value>2028-02-22</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>5665</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>9.88</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F7"/>
            </exerciseDate>
            <expirationDate>
                <value>2029-04-15</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>6474</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>9.88</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F8"/>
            </exerciseDate>
            <expirationDate>
                <value>2029-11-15</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>8093</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>9.76</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F9"/>
            </exerciseDate>
            <expirationDate>
                <value>2030-03-04</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>2787</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>9.76</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F10"/>
            </exerciseDate>
            <expirationDate>
                <value>2030-03-04</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>10521</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Includes 17,025 restricted stock units (&quot;RSUs&quot;), 3,186 of which have vested. Subject to the Reporting Person's continued service to the Issuer, (i) 1,650 RSUs will vest on March 4, 2021 and (ii) 1,315 RSUs will vest on May 15, 2021. All other unvested RSUs will vest in semi-annual installments, subject to the Reporting Person's continued service to the Issuer, (i) beginning on February 15, 2021 and ending on February 15, 2022 for 1,180 RSUs, (ii) beginning on February 15, 2021 and ending on August 15, 2023 for 2,293 RSUs, (iii) beginning on February 15, 2021 and ending on February 15, 2024 for 3,456 RSUs, and (iv) beginning on November 15, 2021 and ending on May 15, 2024 for 3,945 RSUs.</footnote>
        <footnote id="F2">This option represents the right to purchase 13,759 shares of the Issuer's common stock, all of which have vested.</footnote>
        <footnote id="F3">This option represents the right to purchase 4,046 shares of the Issuer's common stock, all of which have vested.</footnote>
        <footnote id="F4">This option represents the right to purchase 4,855 shares of the Issuer's common stock, all of which have vested.</footnote>
        <footnote id="F5">This option represents the right to purchase a total of 6,474 shares of the Issuer's common stock, 5,260 of which have vested, with the remaining shares vesting in equal monthly installments through February 23, 2021, subject to the Reporting Person's continued service to the Issuer.</footnote>
        <footnote id="F6">This option represents the right to purchase a total of 5,665 shares of the Issuer's common stock, 3,304 of which  have vested, with the remaining shares vesting in equal monthly installments through March 15, 2022, subject to the Reporting Person's continued service to the Issuer.</footnote>
        <footnote id="F7">This option represents the right to purchase a total of 6,474 shares of the Issuer's common stock, 1,888 of which vested, with the remaining shares vesting in equal monthly installments through May 15, 2023, subject to the Reporting Person's continued service to the Issuer.</footnote>
        <footnote id="F8">This option represents the right to purchase a total of 8,093 shares of the Issuer's common stock, 1,180 of which have vested, with the remaining shares vesting in equal monthly installments through December 15, 2023, subject to the Reporting Person's continued service to the Issuer.</footnote>
        <footnote id="F9">This option represents the right to purchase 2,787 shares of the Issuer's common stock, all of which have vested.</footnote>
        <footnote id="F10">This option represents the right to purchase a total of 10,521 shares of the Issuer's common stock, 657 of which have vested, with the remaining shares vesting in equal monthly installments through March 15, 2024, subject to the Reporting Person's continued service to the Issuer.</footnote>
    </footnotes>

    <remarks>Exhibit 24 - Power of Attorney</remarks>

    <ownerSignature>
        <signatureName>/s/ Clarke Neumann, Attorney-in-fact for George Gianakopoulos</signatureName>
        <signatureDate>2020-06-18</signatureDate>
    </ownerSignature>
</ownershipDocument>
