<PAGE>   1
                                  UNITED STATES
                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549


                                   FORM 10-K/A
                                 AMENDMENT NO. 2


[X]     ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE
        ACT OF 1934 FOR THE FISCAL YEAR ENDED December 31, 1999

                                       or

[ ]     TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES
        EXCHANGE ACT OF 1934

Commission File Number:  0-22669

                         AURORA BIOSCIENCES CORPORATION
             ------------------------------------------------------
             (Exact name of registrant as specified in its charter)

                Delaware                             33-0669859
    -------------------------------      ------------------------------------
    (State or other jurisdiction of      (I.R.S. Employer Identification No.)
     incorporation or organization)

     11010 Torreyana Road, San Diego, CA                 92121
    ----------------------------------------           ----------
    (Address of principal executive offices)           (Zip code)

                                 (858) 404-6600
--------------------------------------------------------------------------------
              (Registrant's telephone number, including area code)


<TABLE>
<S>                                                              <C>
Securities registered pursuant to Section 12(b) of the Act:      None

Securities registered pursuant to Section 12(g) of the Act:      Common Stock, Par Value $0.001
                                                                 ------------------------------
                                                                      (Title of class)
</TABLE>

Indicate by check mark whether the registrant (1) has filed all reports required
to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during
the preceding 12 months (or such shorter period that the registrant was required
to file such reports), and (2) has been subject to such filing requirements for
the past 90 days. Yes [X]  No [ ]

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405
of Regulation S-K is not contained herein, and will not be contained, to the
best of the registrant's knowledge, in definitive proxy or information
statements incorporated by reference in Part III of this Form 10-K or any
amendment to this Form 10-K. [X]

The aggregate market value of Common Stock held by non-affiliates, based on the
last sale price as reported on the Nasdaq National Market on February 29, 2000,
was approximately $1.98 million*.

The number of shares of registrant's Common Stock outstanding as of February 29,
2000 was 19,677,894.

<PAGE>   2


DOCUMENTS INCORPORATED BY REFERENCE:

Registrant's proxy statement filed in connection with the solicitation of
proxies for its 2000 Annual Meeting of Stockholders is incorporated by reference
into Part III of this Form 10-K. Certain Exhibits filed with the Registrant's
Registration Statement Form S-1 (333-23407), Form 10-Q for the quarter ended
September 30, 1997, Form 10-K for the year ended December 31, 1997, Form 10-Q
for the quarter ended June 30, 1998 and Form 10-Q for the quarter ended March
31, 1999, June 30, 1999 and September 30, 1999 are incorporated by reference
into Part IV of this Form 10-K.

EXPLANATORY STATEMENT:

This Amendment No. 2 to the Annual Report on Form 10-K for Aurora Biosciences
Corporation for the fiscal year ended December 31, 1999 is being filed to amend
Part IV, Item 14(c) to amend Exhibits 10.52 - 10.55.

ITEM 14. EXHIBITS, FINANCIAL STATEMENT SCHEDULES AND REPORTS ON FORM 8-K

(c)     Exhibits

<TABLE>
<CAPTION>
    EXHIBIT
    NUMBER      DESCRIPTION OF DOCUMENT
    -------     -----------------------
<S>             <C>
    3.4(1)      Restated Certificate of Incorporation.

    3.5(1)      Restated Bylaws.

    4.1+        Reference is made to Exhibits 3.4 and 3.5.

    4.2(1)      Form of Common Stock Certificate.

    4.3(1)      Amended and Restated Investors' Rights Agreement dated as of
                December 27, 1996 between the Registrant and the individuals and
                entities listed in the signature pages thereto.

    10.1(1)     Form of Indemnity Agreement entered into between Registrant and
                its directors and officers.

    10.2(1)#    Registrant's 1996 Stock Plan, as amended and restated (the "1996
                Stock Plan").

    10.3(1)#    Form of Incentive Stock Option Agreement under the 1996 Stock
                Plan.

    10.4(1)#    Form of Nonstatutory Stock Option Agreement under the 1996 Stock
                Plan.

    10.5(1)#    Form of Restricted Stock Purchase Agreement under the 1996 Stock
                Plan.

    10.6(1)#    Registrant's Employee Stock Purchase Plan and related offering
                document.

    10.7(1)#    Registrant's Non-Employee Directors' Stock Option Plan.

    10.8(1)#    Form of Nonstatutory Stock Option under Registrant's
                Non-Employee Directors' Stock Option Plan.

    10.9(1)#    Employment Agreement dated January 23, 1996 between the
                Registrant and Timothy J. Rink, as subsequently amended on March
                8, 1996.

    10.10(1)#   Employment Agreement dated August 6, 1996 between the Registrant
                and J. Gordon Foulkes.

    10.11(1)    Preferred Stock Purchase Agreement dated as of March 8, 1996
                between the Registrant and the individuals and entities listed
                in the signature pages thereto.

    10.12(1)    Series D Preferred Stock Purchase Agreement dated as of December
                27, 1996 between the Registrant and the individual and entities
                listed in the signature pages thereto.

    10.13(1)    Sublease dated May 29, 1996 between the Registrant and Torrey
                Pines Science Center Limited Partnership, as subsequently
                amended on August 31, 1996.

    10.14(1)    Master Lease Agreement dated May 17, 1996 between the Registrant
                and Lease Management Services Incorporated.

    10.15(1)    Equipment Financing Agreement dated May 17, 1996 between the
                Registrant and Lease Management Services Incorporated.

    10.16(1)    Security Deposit Pledge Agreement dated May 17, 1996 between the
                Registrant and Lease Management Services Incorporated.

    10.17(1)*   Exclusive License Agreement for Fluorescent Assay Technologies
                dated June 17, 1996 between the Registrant and The Regents of
                the University of California.

    10.18(1)*   License Agreement dated August 2, 1996 between the Registrant
                and California
                Institute of Technology.

    10.19(1)*   License Agreement dated October 4, 1996 between the Registrant
                and the State of Oregon, acting by and through the State Board
                of Higher Education on behalf of the University of Oregon.

    10.20(1)*   Research Agreement dated April 2, 1996 between the Registrant
                and Sequana Therapeutics, Inc.

    10.21(1)*   Collaboration and License Agreement effective as of April 24,
                1996 between the Registrant and Packard Instrument Company, Inc.

    10.22(1)*   Collaborative Research and License Agreement dated November 26,
                1996 between the Registrant and Bristol-Myers Squibb
                Pharmaceutical Research Institute.
</TABLE>


<PAGE>   3

<TABLE>
<CAPTION>
    EXHIBIT
    NUMBER      DESCRIPTION OF DOCUMENT
    -------     -----------------------
<S>             <C>
    10.23(1)*   Collaborative Research and License Agreement dated December 18,
                1996 between the Registrant and Eli Lilly and Company.

    10.24(1)*   Collaboration Agreement effective as of February 1, 1997 between
                the Registrant and Allelix Biopharmaceuticals Inc.

    10.25(1)    Multi-Tenant Industrial Lease dated April 7, 1997 between the
                Registrant and AEW/LBA Acquisition Co. II, LLC., as subsequently
                amended on June 12, 1997.

    10.26(2)    First Amendment dated September 1, 1997, to Multi-Tenant
                Industrial Lease between the Registrant and AEW/LBA Acquisition
                Co. II, LLC.

    10.27(2)*   Collaborative Research and License Agreement dated September 22,
                1997 between the Registrant and Warner-Lambert Company.

    10.28(3)*   Collaborative Research and License Agreement dated December 18,
                1997 between the Registrant and Merck & Co., Inc.

    10.29(3)    Negative Covenant Pledge Agreement dated September 29, 1997
                between the Registrant and Lease Management Services
                Incorporated.

    10.30(3)    Collateral Security Agreement dated December 16, 1997 between
                the Registrant and Lease Management Services Incorporated.

    10.31(3)*   Packard Aurora Supply Agreement dated February 5, 1998 between
                the Registrant and Packard Instrument Company, Inc.

    10.32(3)*   Amendment to Collaboration and License Agreement dated February
                7, 1998, to Collaboration and License Agreement effective as of
                April 24, 1996 between the Registrant and Packard Instrument
                Company, Inc.

    10.33(3)#   Amendment dated January 2, 1998, to Employment Agreement between
                the Registrant and J. Gordon Foulkes.

    10.34(4)*   Combinatorial Chemistry Agreement dated April 25, 1998 between
                the Registrant and SIDDCO, Inc.

    10.35(4)*   Agreement dated June 11, 1998 between the Registrant and J.
                Gordon Foulkes.

    10.36(4)    Agreement dated July 16, 1998 between the Registrant and Deborah
                J. Tower.

    10.37(5)*   Collaborative Research Agreement dated July 16, 1998 between the
                Registrant and Cytovia, Inc.

    10.38(5)*   AMCS Development Agreement dated August 21, 1998 between the
                Registrant and Warner-Lambert Company.

    10.39(6)#   Promissory Note dated February 18, 1997 between the Registrant
                and Harry Stylli.

    10.40(6)#   Terms of employment dated December 3, 1997 between the
                Registrant and Paul J. England.

    10.41(6)#   Terms of employment dated June 9, 1998 between the Registrant
                and Thomas G. Klopack.

    10.42(6)*   Termination Agreement between the Registrant and Packard
                Instrument Company, Inc.

    10.43(6)#   Loan Agreement and Promissory Note dated December 23, 1998
                between the Registrant and Thomas G. Klopack.

    10.44(7)*   Collaborative Research and License Agreement effective as of
                February 5, 1999 between the Registrant and The Pharmacia &
                Upjohn Company.

    10.45(7)*   Collaborative Research and License Agreement effective as of
                February 16, 1999 between the Registrant, F.Hoffmann-LaRoche
                Ltd. and Hoffmann-LaRoche, Inc.

    10.46(7)    Loan and Security Agreement dated February 26, 1999 between the
                Registrant and General Electric Capital Business Asset Funding
                Corporation.

    10.47(7)*   License Agreement effective as of March 10, 1999 between the
                Registrant and Clontech Laboratories, Inc.

    10.48(8)*   Collaborative Research and License Agreement effective as of
                June 15, 1999 between the Registrant and Pfizer Incorporated.

    10.49(9)*   Collaborative Research and License Agreement (Second Amendment)
                effective as of July 29, 1999 between the Registrant and
                Bristol-Myers Squibb Pharmaceuticals Research Institute.

    10.50(9)#   Agreement dated November 2, 1999 between the Registrant and
                Timothy J. Rink, M.D., Sc.D.

    10.51#+     Agreement dated December 7, 1999 between the Registrant and
                Stuart J.M. Collinson, Ph.D.

    10.52**     Third Amendment to Collaborative Research and License Agreement
                effective as of November 22, 1999 between the Registrant and Eli
                Lilly and Company.

    10.53**     Instrument, Assay Development and License Agreement effective as
                of December 15, 1999 between the Registrant and Glaxo Research
                and Development Ltd. and Glaxo Group Ltd.

    10.54**     Instrument, Assay Development and License Agreement effective as
                of December 16, 1999 between the Registrant and Wyeth-Ayerst.

    10.55**     License Agreement effective as of December 17, 1999 between the
                Registrant and ZymoGenetics, Inc.
</TABLE>

<PAGE>   4


<TABLE>
<CAPTION>
    EXHIBIT
    NUMBER      DESCRIPTION OF DOCUMENT
    -------     -----------------------
<S>             <C>

    10.56#+     Agreement effective as of January 1, 2000 between the Registrant
                and Timothy J. Rink, M.D., Sc.D.

    23.1+       Consent of Ernst & Young LLP, Independent Auditors.

    24.1+       Power of Attorney. Reference is made to page 41.

    27.1+       Financial Data Schedule related to the Financial Statements for
                the fiscal year ended December 31, 1999.
</TABLE>

----------

        (1)    Previously filed as exhibits of the same number with the
               Registrant's Registration Statement on Form S-1 (No. 333-23407)
               or amendments thereof, and incorporated herein by reference.

        (2)    Previously filed as exhibits of the same number with the
               Registrant's Quarterly Report on Form 10-Q for the quarter ended
               September 30, 1997 (No. 0-22669) and incorporated herein by
               reference.

        (3)    Previously filed as exhibits of the same number with the
               Registrant's Annual Report on Form 10-K for the fiscal year ended
               December 31, 1997 (No. 0-22669) and incorporated herein by
               reference.

        (4)    Previously filed as exhibits of the same number with the
               Registrant's Quarterly Report on Form 10-Q for the quarter ended
               June 30, 1998 (No. 0-22669) and incorporated herein by reference.

        (5)    Previously filed as exhibits of the same number with the
               Registrant's Quarterly Report on Form 10-Q for the quarter ended
               September 30, 1998 (No. 0-22669) and incorporated herein by
               reference.

        (6)    Previously filed as exhibits of the same number with the
               Registrant's Annual Report on Form 10-K for the fiscal year ended
               December 31, 1998 (No. 0-22669) and incorporated herein by
               reference.

        (7)    Previously filed as exhibits of the same number with the
               Registrant's Quarterly Report on Form 10-Q for the quarter ended
               March 31, 1999 (No. 0-22669) and incorporated herein by
               reference.

        (8)    Previously filed as exhibits of the same number with the
               Registrant's Quarterly Report on Form 10-Q for the quarter ended
               June 30, 1999 (No. 0-22669) and incorporated herein by reference.

        (9)    Previously filed as exhibits of the same number with the
               Registrant's Quarterly Report on Form 10-Q for the quarter ended
               September 30, 1999 (No. 0-22669) and incorporated herein by
               reference.

        *      The Company has been granted confidential treatment with respect
               to certain portions of this exhibit. Omitted portions have been
               filed separately with the Securities and Exchange Commission.

        **     The Company has requested confidential treatment with respect to
               certain portions of this exhibit. Omitted portions have been
               filed separately with the Securities and Exchange Commission.

        #      Indicates management contract or compensatory plan or
               arrangement.

        +      Previously filed.

<PAGE>   5


                                   SIGNATURES

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange
Act of 1934, the registrant has duly caused this report to be signed on its
behalf by the undersigned, thereunto duly authorized, on September 26, 2000.

                                 By:   /s/ STUART J.M. COLLINSON
                                    --------------------------------------------
                                         Stuart J.M. Collinson
                                         President and Chief Executive Officer

Pursuant to the requirements of the Securities Exchange Act of 1934, this report
has been signed by the following persons in the capacities and on the dates
indicated.

<TABLE>
<CAPTION>
                  SIGNATURE                                  TITLE                       DATE
                  ---------                                  -----                       ----
<S>                                           <C>                               <C>
          /s/STUART J.M. COLLINSON            President, Chief Executive        September 26, 2000
----------------------------------------        Officer and Chairman of
        Stuart J.M. Collinson, Ph.D.             the Board (Principal
                                                  Executive Officer)


           /s/JOHN R. PASHKOWKSY*               Vice President, Finance         September 26, 2000
----------------------------------------       (Principal Financial and
             John R. Pashkowsky                   Accounting Officer)


             /s/JAMES C. BLAIR*                        Director                 September 26, 2000
----------------------------------------
            James C. Blair, Ph.D.


         /s/ HUGH Y. RIENHOFF, JR.*                    Director                 September 26, 2000
----------------------------------------
         Hugh Y. Rienhoff, Jr., M.D.


            /s/ROY A. WHITFIELD*                       Director                 September 26, 2000
----------------------------------------
              Roy A. Whitfield


                                                       Director                 September 26, 2000
----------------------------------------
            Timothy J. Wollaeger
</TABLE>


*By /s/ STUART J.M. COLLINSON
    ------------------------------------
     Stuart J.M. Collinson
     Attorney-in-fact