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

                               AMENDMENT NO. 1 ON
                                   FORM 10-K/A

(MARK ONE)

[X]  ANNUAL REPORT PERSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE
ACT OF 1934 FOR THE FISCAL YEAR ENDED DECEMBER 31, 2000 OR

[ ]  TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES
EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM _______________________ TO
_________________________.

COMMISSION FILE #  000-28229

                           CALIPER TECHNOLOGIES CORP.
             (EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)

<TABLE>
<S>                                                <C>
        DELAWARE                                                    33-0675808
(STATE OF INCORPORATION)                           (I.R.S. EMPLOYER IDENTIFICATION NUMBER)
</TABLE>

                               605 FAIRCHILD DRIVE
                          MOUNTAIN VIEW, CA 94043-2234
              (Address and zip code of principal executive offices)

       Registrant's telephone number, including area code: (650) 623-0700

        Securities registered pursuant to Section 12(b) of the Act: None

                    Securities registered pursuant to Section
                               12(g) of the Act:

                         Common Stock, $0.001 Par Value
                                (Title of Class)


     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 for 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 Registrants 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. [ ]

     Based on the closing sale price of common stock on the Nasdaq National
Market on February 15, 2001 the aggregate market value of the voting stock held
by non-affiliates of the registrant was $603,417,389. Excludes an aggregate of
5,108,838 shares of common stock held by officers and directors and by each
person known by the registrant to own 5% or more of the outstanding common
stock. Exclusion of shares held by any of these persons should not be construed
to indicate that such person possesses the power, direct or indirect, to direct
or cause the direction of the management or policies of the registrant, or that
such person is controlled by or under common control with the registrant.


     The number of shares outstanding of Registrant's common stock, $0.001 par
value was 23,855,786 at February 15, 2001.




<PAGE>   2

                       DOCUMENTS INCORPORATED BY REFERENCE

     Certain information in Part III of the Annual Report on Form 10-K, which is
amended by this Form 10-K/A, is incorporated by reference to the Proxy Statement
for the registrant's 2001 Annual Meeting of Stockholders to be filed with the
Securities and Exchange Commission pursuant to Regulation 14A not later than 120
days after the end of the fiscal year covered by the Form 10-K.



<PAGE>   3


                                EXPLANATORY NOTE

     We are filing this amendment to our Annual Report on Form 10-K, originally
filed with the Securities and Exchange Commission on March 16, 2001, solely for
the purpose of adding a change of control plan for members of our senior
management team to the exhibit index under Item 14. The plan was approved by the
Board of Directors in December 2000 and is described further in our Proxy
Statement for the 2001 Annual Meeting of the Stockholders.

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

     (a)  The following documents are filed as a part of this report:

          (1)  FINANCIAL STATEMENTS:                                 PAGE

               Report of Ernst & Young LLP, Independent
               Auditors.............................................. F-2

               Balance Sheets at December 31, 2000 and 1999.......... F-3

               Statements of Operations - Fiscal Years ended
               December 31, 2000, 1999 and 1998...................... F-4

               Statements of Redeemable Convertible Stock and
               Stockholders' Equity - Fiscal Years ended December 31,
               2000, 1999 and 1998................................... F-5

               Statements of Cash flows - Fiscal Years ended
               December 31, 2000, 1999 and 1998...................... F-6

               Notes to Financial Statements......................... F-7

          (2)  FINANCIAL STATEMENT SCHEDULES:

               All schedules are omitted because they are not applicable or the
               required information is shown in the financial statements or
               notes thereto.

          (3)  EXHIBITS:
<TABLE>
<CAPTION>
                EXHIBIT
                NUMBER                                  DESCRIPTION OF DOCUMENT
                -------                                 -----------------------
                <S>            <C>
                 3.1(1)        Amended and Restated Certificate of Incorporation of Caliper.

                 3.2(2)        Bylaws of Caliper.

                 4.1           Reference is made to Exhibits 3.1 and 3.2.

                 4.2(3)        Specimen Stock Certificate.

                10.1(3)        Lease Agreement, dated December 1, 1998, between Caliper and
                               605 East Fairchild Associates, L.P.

                10.2(3)(4)     1996 Equity Incentive Plan.

                10.3(3)(4)     1999 Equity Incentive Plan.

                10.4(3)(4)     1999 Employee Stock Purchase Plan.

                10.5(3)(4)     1999 Non-Employee Directors' Stock Option Plan.

                10.6(3)(4)     Employment Agreement, dated January 18, 1999, between Caliper and Daniel L. Kisner, M.D.

                10.7(3)(4)     Promissory Note, dated July 29, 1999, between Caliper and Daniel L. Kisner, M.D.

                10.8(3)        Amended and Restated Investor Rights Agreement, dated May 7, 1998, among Caliper and
                               certain stockholders of Caliper.

                10.9(3)(4)     Form of Indemnification Agreement entered into between Caliper and its directors and
                               executive officers.

                10.10(3)(5)    Collaboration Agreement, dated May 2, 1998, between Caliper and Hewlett-Packard Company.

                10.11(3)(5)    Termination, Transition and Technology Access Program Agreement, dated November 24, 1998,
                               between Caliper and Hoffmann-La Roche Inc.

                10.12(3)(5)    Technology Access Agreement, dated December 21, 1998, between Caliper and Amgen, Inc.

                10.13(3)(5)    Technology Access Agreement, dated August 12, 1999, between Caliper and Eli Lilly and Company.
</TABLE>

                                       2

<PAGE>   4

<TABLE>
<CAPTION>
                EXHIBIT
                NUMBER                                  DESCRIPTION OF DOCUMENT
                -------                                 -----------------------
                <S>            <C>
                10.14(3)(5)    Screening Collaboration Agreement, dated December 16, 1998, between Caliper and
                               Neurocrine Biosciences, Inc.

                10.15(3)(5)    Sole Commercial Patent License Agreement, effective September 1, 1995, between Lockheed
                               Martin Energy Research Corporation and Caliper, as amended (domestic).

                10.16(3)(5)    Sole Commercial Patent License Agreement, effective September 1, 1995, between
                               Lockheed Martin Energy Research Corporation and Caliper, as amended (international).

                10.17(3)(4)    Consulting Agreement, dated April 30, 1997, between Caliper and Dr. David V. Milligan.

                10.18(3)(4)    Employment Agreement, dated September 23, 1999, between Caliper and James L. Knighton.

                10.19(3)(4)    Consulting Agreement, dated May 1, 1997, between Caliper and Regis McKenna.

                10.20(3)(4)    Promissory Note, dated March 25, 1997, between Caliper and Michael R. Knapp, Ph.D.

                10.21(3)(4)    Option Agreement, dated August 9, 1995, between Caliper and Michael R. Knapp, Ph.D.

                10.22(3)(4)    Amendment to Option Agreement, dated August 25, 1995, between Caliper,
                               Michael R. Knapp, Ph.D., J. Michael Ramsey, Ph.D. and Avalon Medical Partners.

                10.23(3)(4)    The Corporate Plan for Retirement Select Plan Adoption Agreement and related Basic Plan Document.

                10.24(6)       Warrant for the purchase of shares of Common Stock issued to Michael R. Knapp,
                               dated October 11, 1996.

                10.25(6)       Warrant for the purchase of shares of Common Stock issued to Michael R. Knapp,
                               dated February 2, 2000.

                10.26(5)(7)    Technology Access and Applications Development Agreement, dated March 24, 2000, between
                               Caliper and Millennium Pharmaceuticals, Inc.

                10.27(8)       Lease Agreement, dated June 23, 2000 and effective July 5, 2000, between Caliper and
                               Martin CBP Associates, L.P.

                10.28(8)       Promissory Note, dated July 17, 2000, between Caliper and Daniel L. Kisner, M.D.

                10.29(4)       Change of Control Plan.

                23.1(9)        Consent of Ernst & Young LLP, independent auditors.

                24.1(9)        Power of Attorney.
</TABLE>

----------

(1)  Previously filed as Exhibit 3.3 to our Registration Statement on Form S-1,
     as amended, File No. 333-88827, filed on October 12, 1999 and incorporated
     by reference herein.

(2)  Previously filed as Exhibit 3.4 to our Registration Statement on Form S-1,
     as amended, File No. 333-88827, filed on October 12, 1999 and incorporated
     by reference herein.

(3)  Previously filed as the like-numbered Exhibit to our Registration Statement
     on Form S-1, as amended, File No. 333-88827, filed on October 12, 1999 and
     incorporated by reference herein.

(4)  Management contract or compensatory plan or arrangement.

(5)  Confidential treatment has been granted for a portion of this exhibit.

(6)  Previously filed as the like-numbered Exhibit to Annual Report on Form 10-K
     for the year ended December 31, 1999 and incorporated by reference herein.

(7)  Previously filed as Exhibit 10.26 to Form 10-Q for the quarterly period
     ended March 31, 2000 and incorporated by reference herein.

(8)  Previously filed as the like-numbered Exhibit to our Registration Statement
     on Form S-1, as amended, File No. 333-45942, filed on September 15, 2001,
     and incorporated by reference herein.

                                       3

<PAGE>   5


(9)  Previously filed as the like-numbered Exhibits to Annual Report on Form
     10-K for the year ended December 31, 2000 and incorporated by reference
     herein.

     (b)  Reports on Form 8-K

     No Current Report was filed during the three months ended December 31,
2000.


                                       4

<PAGE>   6


                                   SIGNATURES

     Pursuant to the requirements of Section 13 or 15(d) of the Securities
Exchange Act of 1934, the Registrant has duly caused this Amendment to Report to
be signed on its behalf by the undersigned, thereunto duly authorized, on April
23, 2001.

                                       CALIPER TECHNOLOGIES CORP.


                                       By: DANIEL L. KISNER*
                                           -------------------------------------
                                           Daniel L. Kisner, M.D.
                                           President and Chief Executive Officer

<TABLE>
<CAPTION>
             SIGNATURES                                             TITLE                                   DATE
             ----------                                             -----                                   ----
<S>                                         <C>                                                        <C>
          DANIEL L. KISNER*                    President, Chief Executive Officer and Director         April 23, 2001
----------------------------------------                (principal executive officer)
       Daniel L. Kisner, M.D.

        /s/ JAMES L. KNIGHTON               Executive Vice President and Chief Financial Officer       April 23, 2001
----------------------------------------                (principal financial officer)
          James L. Knighton

        ANTHONY HENDRICKSON*                                Corporate Controller                       April 23, 2001
----------------------------------------               (principal accounting officer)
         Anthony Hendrickson

         DAVID V. MILLIGAN*                          Chairman of the Board of Directors                April 23, 2001
----------------------------------------
      David V. Milligan, Ph.D.

          ANTHONY B. EVNIN*                                       Director                             April 23, 2001
----------------------------------------
       Anthony B. Evnin, Ph.D.

         CHARLES M. HARTMAN*                                      Director                             April 23, 2001
----------------------------------------
         Charles M. Hartman

          REGIS P. MCKENNA*                                       Director                             April 23, 2001
----------------------------------------
          Regis P. McKenna

          ROBERT T. NELSEN*                                       Director                             April 23, 2001
----------------------------------------
          Robert T. Nelsen

         MICHAEL STEINMETZ*                                       Director                             April 23, 2001
----------------------------------------
      Michael Steinmetz, Ph.D.


* By: /s/ JAMES L. KNIGHTON
     -----------------------------------
     James L. Knighton
     Attorney-in-Fact
</TABLE>


                                       6

<PAGE>   7


                                  EXHIBIT INDEX

<TABLE>
<CAPTION>
EXHIBIT
NUMBER                                  DESCRIPTION OF DOCUMENT
-------                                 -----------------------
<S>            <C>
 3.1(1)        Amended and Restated Certificate of Incorporation of Caliper.

 3.2(2)        Bylaws of Caliper.

 4.1           Reference is made to Exhibits 3.1 and 3.2.

 4.2(3)        Specimen Stock Certificate.

10.1(3)        Lease Agreement, dated December 1, 1998, between Caliper and
               605 East Fairchild Associates, L.P.

10.2(3)(4)     1996 Equity Incentive Plan.

10.3(3)(4)     1999 Equity Incentive Plan.

10.4(3)(4)     1999 Employee Stock Purchase Plan.

10.5(3)(4)     1999 Non-Employee Directors' Stock Option Plan.

10.6(3)(4)     Employment Agreement, dated January 18, 1999, between Caliper and Daniel L. Kisner, M.D.

10.7(3)(4)     Promissory Note, dated July 29, 1999, between Caliper and Daniel L. Kisner, M.D.

10.8(3)        Amended and Restated Investor Rights Agreement, dated May 7, 1998, among Caliper and
               certain stockholders of Caliper.

10.9(3)(4)     Form of Indemnification Agreement entered into between Caliper and its directors and
               executive officers.

10.10(3)(5)    Collaboration Agreement, dated May 2, 1998, between Caliper and Hewlett-Packard Company.

10.11(3)(5)    Termination, Transition and Technology Access Program Agreement, dated November 24, 1998,
               between Caliper and Hoffmann-La Roche Inc.

10.12(3)(5)    Technology Access Agreement, dated December 21, 1998, between Caliper and Amgen, Inc.

10.13(3)(5)    Technology Access Agreement, dated August 12, 1999, between Caliper and Eli Lilly and Company.

10.14(3)(5)    Screening Collaboration Agreement, dated December 16, 1998, between Caliper and
               Neurocrine Biosciences, Inc.

10.15(3)(5)    Sole Commercial Patent License Agreement, effective September 1, 1995, between Lockheed
               Martin Energy Research Corporation and Caliper, as amended (domestic).

10.16(3)(5)    Sole Commercial Patent License Agreement, effective September 1, 1995, between
               Lockheed Martin Energy Research Corporation and Caliper, as amended (international).

10.17(3)(4)    Consulting Agreement, dated April 30, 1997, between Caliper and Dr. David V. Milligan.

10.18(3)(4)    Employment Agreement, dated September 23, 1999, between Caliper and James L. Knighton.

10.19(3)(4)    Consulting Agreement, dated May 1, 1997, between Caliper and Regis McKenna.

10.20(3)(4)    Promissory Note, dated March 25, 1997, between Caliper and Michael R. Knapp, Ph.D.

10.21(3)(4)    Option Agreement, dated August 9, 1995, between Caliper and Michael R. Knapp, Ph.D.

10.22(3)(4)    Amendment to Option Agreement, dated August 25, 1995, between Caliper,
               Michael R. Knapp, Ph.D., J. Michael Ramsey, Ph.D. and Avalon Medical Partners.

10.23(3)(4)    The Corporate Plan for Retirement Select Plan Adoption Agreement and related Basic Plan Document.

10.24(6)       Warrant for the purchase of shares of Common Stock issued to Michael R. Knapp,
               dated October 11, 1996.

10.25(6)       Warrant for the purchase of shares of Common Stock issued to Michael R. Knapp,
               dated February 2, 2000.

10.26(5)(7)    Technology Access and Applications Development Agreement, dated March 24, 2000, between
               Caliper and Millennium Pharmaceuticals, Inc.

10.27(8)       Lease Agreement, dated June 23, 2000 and effective July 5, 2000, between Caliper and
               Martin CBP Associates, L.P.

10.28(8)       Promissory Note, dated July 17, 2000, between Caliper and Daniel L. Kisner, M.D.

10.29(4)       Change of Control Plan.

23.1(9)        Consent of Ernst & Young LLP, independent auditors.
</TABLE>

<PAGE>   8

<TABLE>
<CAPTION>
EXHIBIT
NUMBER                         DESCRIPTION OF DOCUMENT
-------                       -----------------------
<S>            <C>
24.1(9)        Power of Attorney.
</TABLE>

----------

(1)  Previously filed as Exhibit 3.3 to our Registration Statement on Form S-1,
     as amended, File No. 333-88827, filed on October 12, 1999 and incorporated
     by reference herein.

(2)  Previously filed as Exhibit 3.4 to our Registration Statement on Form S-1,
     as amended, File No. 333-88827, filed on October 12, 1999 and incorporated
     by reference herein.

(3)  Previously filed as the like-numbered Exhibit to our Registration Statement
     on Form S-1, as amended, File No. 333-88827, filed on October 12, 1999 and
     incorporated by reference herein.

(4)  Management contract or compensatory plan or arrangement.

(5)  Confidential treatment has been granted for a portion of this exhibit.

(6)  Previously filed as the like-numbered Exhibit to Annual Report on Form 10-K
     for the year ended December 31, 1999 and incorporated by reference herein.

(7)  Previously filed as Exhibit 10.26 to Form 10-Q for the quarterly period
     ended March 31, 2000 and incorporated by reference herein.

(8)  Previously filed as the like-numbered Exhibit to our Registration Statement
     on Form S-1, as amended, File No. 333-45942, filed on September 15, 2001,
     and incorporated by reference herein.

(9)  Previously filed as the like-numbered Exhibits to Annual Report on Form
     10-K for the year ended December 31, 2000 and incorporated by reference
     herein.