| 2000-04-04 | vs HOU | 1 | L 2-5 | 0-1 | 6 | 54,399 | Jason Schmidt | Shane Reynolds | Shane Reynolds | Jason Schmidt | Billy Wagner | 2 | 5 | -3 |
| 2000-04-05 | vs HOU | 2 | L 2-11 | 0-2 | 6 | 12,208 | Kris Benson | Jose Lima | Jose Lima | Kris Benson | | 4 | 16 | -12 |
| 2000-04-06 | vs HOU | 3 | W 10-1 | 1-2 | 5 | 11,860 | Francisco Cordova | Chris Holt | Francisco Cordova | Chris Holt | | 14 | 17 | -3 |
| 2000-04-07 | @ ARI | 4 | W 7-2 | 2-2 | 4 | 32,536 | Todd Ritchie | Armando Reynoso | Jason Christiansen | Armando Reynoso | | 21 | 19 | 2 |
| 2000-04-08 | @ ARI | 5 | L 5-6 | 2-3 | 5 | 33,298 | Jimmy Anderson | Brian Anderson | Greg Swindell | Jason Christiansen | | 26 | 25 | 1 |
| 2000-04-09 | @ ARI | 6 | L 0-1 | 2-4 | 5 | 34,204 | Jason Schmidt | Randy Johnson | Randy Johnson | Jason Schmidt | | 26 | 26 | 0 |
| 2000-04-11 | vs MON | 7 | L 3-7 | 2-5 | 6 | 11,335 | Kris Benson | Javier Vazquez | Javier Vazquez | Kris Benson | Steve Kline | 29 | 33 | -4 |
| 2000-04-12 | vs MON | 8 | W 6-4 | 3-5 | 6 | 10,290 | Francisco Cordova | Carl Pavano | Jose Silva | Miguel Batista | Mike Williams | 35 | 37 | -2 |
| 2000-04-13 | vs MON | 9 | W 4-3 | 4-5 | 6 | 11,162 | Todd Ritchie | Jeremy Powell | Jose Silva | Ugueth Urbina | | 39 | 40 | -1 |
| 2000-04-14 | vs NYN | 10 | L 5-8 | 4-6 | 6 | 20,725 | Jason Schmidt | Al Leiter | John Franco | Jose Silva | | 44 | 48 | -4 |
| 2000-04-15 | vs NYN | 11 | W 2-0 | 5-6 | 6 | 19,592 | Jimmy Anderson | Glendon Rusch | Jimmy Anderson | Glendon Rusch | Mike Williams | 46 | 48 | -2 |
| 2000-04-16 | vs NYN | 12 | L 9-12 | 5-7 | 6 | 20,724 | Kris Benson | Robert Joseph Jones | Pat Mahomes | Chris Peters | Armando Benitez | 55 | 60 | -5 |
| 2000-04-18 | @ FLO | 13 | L 5-12 | 5-8 | 5 | 9,494 | Francisco Cordova | Brad Penny | Brad Penny | Francisco Cordova | | 60 | 72 | -12 |
| 2000-04-19 | @ FLO | 14 | W 5-1 | 6-8 | 4 | 10,911 | Todd Ritchie | Alex Fernandez | Todd Ritchie | Alex Fernandez | | 65 | 73 | -8 |
| 2000-04-20 | @ FLO | 15 | L 2-3 | 6-9 | 4 | 9,396 | Jimmy Anderson | Ryan Dempster | Vic Darensbourg | Mike Williams | | 67 | 76 | -9 |
| 2000-04-21 | @ ATL | 16 | L 2-6 | 6-10 | 5 | 33,790 | Jose Parra | Terry Mulholland | Terry Mulholland | Mike Garcia | | 69 | 82 | -13 |
| 2000-04-22 | @ ATL | 17 | L 2-4 | 6-11 | 5 | 41,389 | Kris Benson | John Burkett | Bruce Chen | Kris Benson | John Rocker | 71 | 86 | -15 |
| 2000-04-23 | @ ATL | 18 | L 3-5 | 6-12 | 6 | 29,463 | Francisco Cordova | Greg Maddux | Greg Maddux | Francisco Cordova | John Rocker | 74 | 91 | -17 |
| 2000-04-25 | vs SDN | 19 | W 4-3 | 7-12 | 4 | 12,295 | Todd Ritchie | Sterling Hitchcock | Scott Sauerbeck | Carlos Almanzar | | 78 | 94 | -16 |
| 2000-04-26 | vs SDN | 20 | W 9-8 | 8-12 | 3 | 13,765 | Jimmy Anderson | Woody Williams | Mike Williams | Matt Whisenant | | 87 | 102 | -15 |
| 2000-04-27 | vs SDN | 21 | L 4-12 | 8-13 | 3 | 15,459 | Jose Parra | Matt Clement | Matt Clement | Jose Parra | | 91 | 114 | -23 |
| 2000-04-28 | vs CIN | 22 | W 2-1 | 9-13 | 3 | 25,557 | Kris Benson | Pete Harnisch | Kris Benson | Pete Harnisch | Mike Williams | 93 | 115 | -22 |
| 2000-04-29 | vs CIN | 23 | L 5-6 | 9-14 | 4 | 28,731 | Francisco Cordova | Ron Villone | Scott Williamson | Jason Christiansen | Danny Graves | 98 | 121 | -23 |
| 2000-04-30 | vs CIN | 24 | L 2-6 | 9-15 | 4 | 29,728 | Todd Ritchie | Rob Bell | Rob Bell | Todd Ritchie | Scott Williamson | 100 | 127 | -27 |
| 2000-05-02 | @ SLN | 25 | W 10-7 | 10-15 | 4 | 38,588 | Jason Schmidt | Rick Ankiel | Jeff Wallace | Heathcliff Slocumb | | 110 | 134 | -24 |
| 2000-05-03 | @ SLN | 26 | W 8-2 | 11-15 | 3 | 32,270 | Kris Benson | Pat Hentgen | Kris Benson | Pat Hentgen | | 118 | 136 | -18 |
| 2000-05-04 | @ SLN | 27 | L 0-5 | 11-16 | 4 | 45,994 | Francisco Cordova | Garrett Stephenson | Garrett Stephenson | Francisco Cordova | | 118 | 141 | -23 |
| 2000-05-05 | @ CHN | 28 | W 4-2 | 12-16 | 3 | 26,689 | Todd Ritchie | Kevin Tapani | Todd Ritchie | Kevin Tapani | Mike Williams | 122 | 143 | -21 |
| 2000-05-06 | @ CHN | 29 | W 11-9 | 13-16 | 3 | 38,957 | Jimmy Anderson | Scott Downs | Jeff Wallace | Kyle Farnsworth | Mike Williams | 133 | 152 | -19 |
| 2000-05-07 | @ CHN | 30 | W 11-3 | 14-16 | 3 | 38,307 | Jason Schmidt | Kerry Wood | Jason Schmidt | Kerry Wood | | 144 | 155 | -11 |
| 2000-05-09 | vs NYN | 31 | L 0-2 | 14-17 | 3 | 14,015 | Kris Benson | Mike Hampton | Mike Hampton | Kris Benson | Armando Benitez | 144 | 157 | -13 |
| 2000-05-10 | vs NYN | 32 | W 13-9 | 15-17 | 3 | 13,711 | Todd Ritchie | Rick Reed | Jose Silva | Dennis Cook | | 157 | 166 | -9 |
| 2000-05-11 | vs NYN | 33 | L 2-3 | 15-18 | 3 | 16,264 | Jimmy Anderson | Al Leiter | Al Leiter | Jimmy Anderson | | 159 | 169 | -10 |
| 2000-05-12 | vs MIL | 34 | L 1-6 | 15-19 | 3 | 18,524 | Jason Schmidt | Jimmy Haynes | Jimmy Haynes | Jason Schmidt | | 160 | 175 | -15 |
| 2000-05-13 | vs MIL | 35 | W 11-8 | 16-19 | 3 | 26,682 | Brian O'Connor | Horacio Estrada | Scott Sauerbeck | Juan Acevedo | Mike Williams | 171 | 183 | -12 |
| 2000-05-14 | vs MIL | 36 | W 3-0 | 17-19 | 3 | 19,657 | Kris Benson | Jeff D'Amico | Kris Benson | Jeff D'Amico | Jason Christiansen | 174 | 183 | -9 |
| 2000-05-16 | @ CIN | 37 | L 2-6 | 17-20 | 3 | 26,271 | Todd Ritchie | Rob Bell | Rob Bell | Todd Ritchie | | 176 | 189 | -13 |
| 2000-05-17 | @ CIN | 38 | W 9-6 | 18-20 | 3 | 23,193 | Jimmy Anderson | Denny Neagle | Jose Silva | Scott Sullivan | | 185 | 195 | -10 |
| 2000-05-18 | @ CIN | 39 | L 3-4 | 18-21 | 3 | 26,252 | Jason Schmidt | Osvaldo Fernandez | Danny Graves | Mike Garcia | | 188 | 199 | -11 |
| 2000-05-19 | vs SLN | 40 | W 13-1 | 19-21 | 3 | 24,281 | Kris Benson | Rick Ankiel | Kris Benson | Rick Ankiel | | 201 | 200 | 1 |
| 2000-05-20 | vs SLN | 41 | L 4-19 | 19-22 | 3 | 36,331 | Francisco Cordova | Pat Hentgen | Pat Hentgen | Francisco Cordova | | 205 | 219 | -14 |
| 2000-05-21 | vs SLN | 42 | L 5-7 | 19-23 | 3 | 33,034 | Todd Ritchie | Andy Benes | Andy Benes | Todd Ritchie | Dave Veres | 210 | 226 | -16 |
| 2000-05-23 | @ ARI | 43 | L 1-6 | 19-24 | 3 | 31,726 | Jimmy Anderson | Brian Anderson | Brian Anderson | Jimmy Anderson | | 211 | 232 | -21 |
| 2000-05-24 | @ ARI | 44 | L 5-6 | 19-25 | 3 | 30,462 | Jason Schmidt | Todd Stottlemyre | Todd Stottlemyre | Jason Schmidt | Byung-Hyun Kim | 216 | 238 | -22 |
| 2000-05-25 | @ ARI | 45 | L 5-7 | 19-26 | 3 | 30,759 | Kris Benson | Omar Daal | Omar Daal | Kris Benson | Matt Mantei | 221 | 245 | -24 |
| 2000-05-26 | @ COL | 46 | W 2-1 | 20-26 | 3 | 40,188 | Francisco Cordova | Masato Yoshii | Francisco Cordova | Masato Yoshii | Mike Williams | 223 | 246 | -23 |
| 2000-05-27 | @ COL | 47 | L 6-7 | 20-27 | 3 | 42,184 | Todd Ritchie | Scott Karl | Gabe White | Jason Christiansen | | 229 | 253 | -24 |
| 2000-05-28 | @ COL | 48 | L 2-11 | 20-28 | 3 | 41,641 | Jimmy Anderson | Rolando Arrojo | Rolando Arrojo | Jimmy Anderson | | 231 | 264 | -33 |
| 2000-05-29 | vs FLO | 49 | W 10-4 | 21-28 | 3 | 17,282 | Jason Schmidt | Vladimir Nunez | Jason Schmidt | Vladimir Nunez | | 241 | 268 | -27 |
| 2000-05-30 | vs FLO | 50 | W 3-2 | 22-28 | 3 | 14,742 | Kris Benson | Reid Cornelius | Mike Williams | Antonio Alfonseca | | 244 | 270 | -26 |
| 2000-05-31 | vs FLO | 51 | W 5-2 | 23-28 | 3 | 17,731 | Francisco Cordova | Jesus Sanchez | Francisco Cordova | Jesus Sanchez | Mike Williams | 249 | 272 | -23 |
| 2000-06-02 | vs KCA | 52 | W 9-3 | 24-28 | 3 | 23,527 | Todd Ritchie | Miguel Batista | Todd Ritchie | Miguel Batista | | 258 | 275 | -17 |
| 2000-06-03 | vs KCA | 53 | L 3-16 | 24-29 | 3 | 26,264 | Jason Schmidt | Jay Witasick | Jay Witasick | Jason Schmidt | | 261 | 291 | -30 |
| 2000-06-04 | vs KCA | 54 | L 5-7 | 24-30 | 3 | 27,915 | Kris Benson | Jeff Suppan | Jason Rakers | Jason Christiansen | Dan Reichert | 266 | 298 | -32 |
| 2000-06-05 | vs DET | 55 | W 5-1 | 25-30 | 3 | 12,479 | Francisco Cordova | Dave Mlicki | Francisco Cordova | Dave Mlicki | | 271 | 299 | -28 |
| 2000-06-06 | vs DET | 56 | L 1-2 | 25-31 | 3 | 13,174 | Jimmy Anderson | Willie Blair | C.J. Nitkowski | Jimmy Anderson | Todd Jones | 272 | 301 | -29 |
| 2000-06-07 | vs DET | 57 | W 4-3 | 26-31 | 3 | 15,067 | Todd Ritchie | Hideo Nomo | Todd Ritchie | Hideo Nomo | Mike Williams | 276 | 304 | -28 |
| 2000-06-09 | @ KCA | 58 | L 5-6 | 26-32 | 3 | 30,963 | Jason Schmidt | Jeff Suppan | Jerry Spradlin | Jason Christiansen | | 281 | 310 | -29 |
| 2000-06-10 | @ KCA | 59 | L 1-2 | 26-33 | 3 | 34,868 | Kris Benson | Mac Suzuki | Ricky Bottalico | Jose Silva | | 282 | 312 | -30 |
| 2000-06-11 | @ KCA | 60 | W 10-6 | 27-33 | 3 | 26,495 | Francisco Cordova | Jay Witasick | Scott Sauerbeck | Jerry Spradlin | | 292 | 318 | -26 |
| 2000-06-12 | vs ATL | 61 | L 8-10 | 27-34 | 3 | 15,196 | Todd Ritchie | Kevin Millwood | Kerry Ligtenberg | Jason Christiansen | Mike Remlinger | 300 | 328 | -28 |
| 2000-06-13 | vs ATL | 62 | W 7-6 | 28-34 | 3 | 17,971 | Bronson Arroyo | John Burkett | Jose Silva | Don Wengert | | 307 | 334 | -27 |
| 2000-06-14 | vs ATL | 63 | L 4-8 | 28-35 | 3 | 16,972 | Jimmy Anderson | Greg Maddux | Greg Maddux | Jimmy Anderson | Kerry Ligtenberg | 311 | 342 | -31 |
| 2000-06-15 | vs ATL | 64 | W 2-0 | 29-35 | 3 | 19,065 | Kris Benson | Kevin Millwood | Kris Benson | Kevin Millwood | | 313 | 342 | -29 |
| 2000-06-16 | vs FLO | 65 | L 3-8 | 29-36 | 3 | 29,737 | Francisco Cordova | Reid Cornelius | Reid Cornelius | Francisco Cordova | Braden Looper | 316 | 350 | -34 |
| 2000-06-17 | vs FLO | 66 | L 3-4 | 29-37 | 3 | 23,552 | Todd Ritchie | Jesus Sanchez | Antonio Alfonseca | Rich Loiselle | Joe Strong | 319 | 354 | -35 |
| 2000-06-18 | vs FLO | 67 | L 4-5 | 29-38 | 3 | 24,916 | Bronson Arroyo | Brad Penny | Ricky Bones | Jason Christiansen | Antonio Alfonseca | 323 | 359 | -36 |
| 2000-06-19 | @ MON | 68 | L 1-2 | 29-39 | 4 | 7,483 | Jose Silva | Carl Pavano | Carl Pavano | Rich Loiselle | Steve Kline | 324 | 361 | -37 |
| 2000-06-20 | @ MON | 69 | W 2-1 | 30-39 | 3 | 8,056 | Kris Benson | Mike Johnson | Kris Benson | Mike Johnson | Mike Williams | 326 | 362 | -36 |
| 2000-06-21 | @ MON | 70 | W 8-3 | 31-39 | 3 | 8,324 | Francisco Cordova | Tony Armas | Francisco Cordova | Tony Armas | Chris Peters | 334 | 365 | -31 |
| 2000-06-22 | @ MON | 71 | L 5-6 | 31-40 | 3 | 8,635 | Todd Ritchie | Dustin Hermanson | Dustin Hermanson | Todd Ritchie | Anthony Telford | 339 | 371 | -32 |
| 2000-06-23 | @ NYN | 72 | L 2-12 | 31-41 | 3 | 39,849 | Bronson Arroyo | Robert Joseph Jones | Robert Joseph Jones | Bronson Arroyo | | 341 | 383 | -42 |
| 2000-06-24 | @ NYN | 73 | L 8-10 | 31-42 | 3 | 34,894 | Jose Silva | Rick Reed | John Franco | Rich Loiselle | Armando Benitez | 349 | 393 | -44 |
| 2000-06-25 | @ NYN | 74 | L 0-9 | 31-43 | 3 | 38,984 | Kris Benson | Mike Hampton | Mike Hampton | Kris Benson | | 349 | 402 | -53 |
| 2000-06-27 | vs CHN | 75 | W 6-0 | 32-43 | 3 | 18,688 | Todd Ritchie | Kerry Wood | Todd Ritchie | Kerry Wood | | 355 | 402 | -47 |
| 2000-06-28 | vs CHN | 76 | L 4-5 | 32-44 | 3 | 29,665 | Francisco Cordova | Jon Lieber | Jon Lieber | Francisco Cordova | Rick Aguilera | 359 | 407 | -48 |
| 2000-06-29 | vs CHN | 77 | W 5-4 | 33-44 | 3 | 19,531 | Jose Silva | Kevin Tapani | Marc Wilkins | Tim Worrell | | 364 | 411 | -47 |
| 2000-06-30 | @ PHI | 78 | W 8-3 | 34-44 | 3 | 38,221 | Kris Benson | Randy Wolf | Kris Benson | Randy Wolf | | 372 | 414 | -42 |
| 2000-07-01 | @ PHI | 79 | L 3-4 | 34-45 | 3 | 48,406 | Bronson Arroyo | Paul Byrd | Paul Byrd | Bronson Arroyo | Jeff Brantley | 375 | 418 | -43 |
| 2000-07-02 | @ PHI | 80 | L 1-9 | 34-46 | 3 | 20,290 | Todd Ritchie | Curt Schilling | Curt Schilling | Todd Ritchie | | 376 | 427 | -51 |
| 2000-07-03 | @ CHN | 81 | L 0-3 | 34-47 | 3 | 40,524 | Francisco Cordova | Jon Lieber | Jon Lieber | Francisco Cordova | | 376 | 430 | -54 |
| 2000-07-04 | @ CHN | 82 | W 10-4 | 35-47 | 3 | 37,043 | Jose Silva | Kevin Tapani | Marc Wilkins | Rick Aguilera | | 386 | 434 | -48 |
| 2000-07-05 | @ CHN | 83 | W 9-6 | 36-47 | 3 | 35,391 | Jimmy Anderson | Scott Downs | Jimmy Anderson | Scott Downs | | 395 | 440 | -45 |
| 2000-07-07 | vs MIN | 84 | W 8-6 | 37-47 | 3 | 22,134 | Todd Ritchie | Joe Mays | Jason Christiansen | Bob Wells | Mike Williams | 403 | 446 | -43 |
| 2000-07-08 | vs MIN | 85 | W 4-1 | 38-47 | 3 | 33,814 | Kris Benson | Eric Milton | Kris Benson | Eric Milton | Mike Williams | 407 | 447 | -40 |
| 2000-07-09 | vs MIN | 86 | L 2-3 | 38-48 | 3 | 23,154 | Jose Silva | Mark Redman | Mark Redman | Jose Silva | LaTroy Hawkins | 409 | 450 | -41 |
| 2000-07-13 | @ CLE | 87 | L 3-4 | 38-49 | 3 | 43,225 | Todd Ritchie | Dave Burba | Steve Karsay | Scott Sauerbeck | | 412 | 454 | -42 |
| 2000-07-14 | @ CLE | 88 | L 3-9 | 38-50 | 3 | 43,046 | Kris Benson | Chuck Finley | Chuck Finley | Kris Benson | | 415 | 463 | -48 |
| 2000-07-15 | @ CLE | 89 | L 4-6 | 38-51 | 3 | 43,049 | Jose Silva | Jim Brower | Jamie Brewington | Jose Silva | Steve Karsay | 419 | 469 | -50 |
| 2000-07-16 | @ LAN | 90 | L 3-7 | 38-52 | 4 | 34,116 | Jimmy Anderson | Eric Gagne | Terry Adams | Mike Williams | | 422 | 476 | -54 |
| 2000-07-17 | @ LAN | 91 | L 6-9 | 38-53 | 4 | 25,261 | Bronson Arroyo | Darren Dreifort | Darren Dreifort | Bronson Arroyo | Jeff Shaw | 428 | 485 | -57 |
| 2000-07-18 | @ LAN | 92 | W 8-6 | 39-53 | 4 | 34,872 | Todd Ritchie | Mike Judd | Josias Manzanillo | Mike Judd | Mike Williams | 436 | 491 | -55 |
| 2000-07-19 | @ MIL | 93 | L 0-6 | 39-54 | 4 | 20,840 | Kris Benson | Jeff D'Amico | Jeff D'Amico | Kris Benson | | 436 | 497 | -61 |
| 2000-07-20 | @ MIL | 94 | W 9-2 | 40-54 | 4 | 29,389 | Jose Silva | Jimmy Haynes | Jose Silva | Jimmy Haynes | | 445 | 499 | -54 |
| 2000-07-21 | vs PHI | 95 | W 9-2 | 41-54 | 4 | 22,438 | Jimmy Anderson | Paul Byrd | Jimmy Anderson | Paul Byrd | | 454 | 501 | -47 |
| 2000-07-22 | vs PHI | 96 | W 2-1 | 42-54 | 4 | 28,485 | Bronson Arroyo | Robert Person | Bronson Arroyo | Robert Person | Mike Williams | 456 | 502 | -46 |
| 2000-07-23 | vs PHI | 97 | L 1-4 | 42-55 | 4 | 23,840 | Todd Ritchie | Curt Schilling | Curt Schilling | Todd Ritchie | | 457 | 506 | -49 |
| 2000-07-25 | vs MIL | 98 | L 1-4 | 42-56 | 4 | 15,808 | Kris Benson | Jeff D'Amico | Curt Leskanic | Jason Christiansen | Bob Wickman | 458 | 510 | -52 |
| 2000-07-26 | vs MIL | 99 | W 5-4 | 43-56 | 4 | 20,421 | Jose Silva | Jimmy Haynes | Jose Silva | Jimmy Haynes | Mike Williams | 463 | 514 | -51 |
| 2000-07-27 | vs MIL | 100 | L 3-4 | 43-57 | 4 | 16,636 | Jimmy Anderson | John Snyder | Curt Leskanic | Josias Manzanillo | Bob Wickman | 466 | 518 | -52 |
| 2000-07-28 | vs SDN | 101 | W 16-5 | 44-57 | 4 | 20,686 | Bronson Arroyo | Matt Clement | Bronson Arroyo | Matt Clement | | 482 | 523 | -41 |
| 2000-07-29 | vs SDN | 102 | W 10-2 | 45-57 | 4 | 30,118 | Francisco Cordova | Brian Tollberg | Francisco Cordova | Brian Tollberg | | 492 | 525 | -33 |
| 2000-07-30 | vs SDN | 103 | L 8-9 | 45-58 | 4 | 19,680 | Kris Benson | Brian Meadows | Donne Wall | Marc Wilkins | Trevor Hoffman | 500 | 534 | -34 |
| 2000-08-01 | vs LAN | 104 | W 6-0 | 46-59 | 4 | 0 | Jimmy Anderson | Carlos Perez | Jimmy Anderson | Carlos Perez | | 506 | 534 | -28 |
| 2000-08-01 | vs LAN | 105 | L 3-5 | 46-59 | 4 | 21,028 | Bronson Arroyo | Ismael Valdez | Matt Herges | Marc Wilkins | Jeff Shaw | 509 | 539 | -30 |
| 2000-08-02 | vs LAN | 106 | L 5-11 | 46-60 | 4 | 19,537 | Jose Silva | Darren Dreifort | Darren Dreifort | Jose Silva | | 514 | 550 | -36 |
| 2000-08-03 | @ SFN | 107 | L 2-10 | 46-61 | 4 | 40,930 | Francisco Cordova | Russ Ortiz | Russ Ortiz | Francisco Cordova | | 516 | 560 | -44 |
| 2000-08-04 | @ SFN | 108 | L 3-5 | 46-62 | 4 | 40,930 | Kris Benson | Kirk Rueter | Doug Henry | Kris Benson | Robb Nen | 519 | 565 | -46 |
| 2000-08-05 | @ SFN | 109 | W 7-2 | 47-62 | 4 | 40,930 | Dan Serafini | Mark Gardner | Dan Serafini | Mark Gardner | | 526 | 567 | -41 |
| 2000-08-06 | @ SFN | 110 | L 1-7 | 47-63 | 4 | 40,930 | Bronson Arroyo | Shawn Estes | Shawn Estes | Bronson Arroyo | | 527 | 574 | -47 |
| 2000-08-07 | @ COL | 111 | W 8-7 | 48-63 | 4 | 39,691 | Jimmy Anderson | Masato Yoshii | Scott Sauerbeck | Jose Jimenez | Mike Williams | 535 | 581 | -46 |
| 2000-08-08 | @ COL | 112 | L 1-6 | 48-64 | 4 | 38,535 | Jose Silva | Brian Rose | Brian Rose | Jose Silva | | 536 | 587 | -51 |
| 2000-08-09 | @ COL | 113 | L 3-4 | 48-65 | 4 | 39,328 | Kris Benson | Julian Tavarez | Gabe White | Mike Williams | | 539 | 591 | -52 |
| 2000-08-11 | vs ARI | 114 | L 1-6 | 48-66 | 4 | 25,281 | Dan Serafini | Armando Reynoso | Armando Reynoso | Dan Serafini | | 540 | 597 | -57 |
| 2000-08-12 | vs ARI | 115 | W 9-6 | 49-66 | 4 | 34,101 | Todd Ritchie | Curt Schilling | Scott Sauerbeck | Curt Schilling | | 549 | 603 | -54 |
| 2000-08-13 | vs ARI | 116 | L 6-7 | 49-67 | 4 | 25,321 | Jimmy Anderson | Brian Anderson | Mike Morgan | Bronson Arroyo | Matt Mantei | 555 | 610 | -55 |
| 2000-08-14 | @ HOU | 117 | L 2-16 | 49-68 | 4 | 30,220 | Jose Silva | Chris Holt | Chris Holt | Jose Silva | | 557 | 626 | -69 |
| 2000-08-15 | @ HOU | 118 | L 4-5 | 49-69 | 5 | 30,020 | Kris Benson | Jose Lima | Jose Lima | Kris Benson | Octavio Dotel | 561 | 631 | -70 |
| 2000-08-16 | @ HOU | 119 | L 10-11 | 49-70 | 5 | 30,165 | Dan Serafini | Scott Elarton | Scott Elarton | Dan Serafini | Octavio Dotel | 571 | 642 | -71 |
| 2000-08-18 | @ CIN | 120 | W 6-3 | 50-70 | 5 | 31,891 | Todd Ritchie | Scott Williamson | Todd Ritchie | Scott Sullivan | Mike Williams | 577 | 645 | -68 |
| 2000-08-19 | @ CIN | 121 | L 1-7 | 50-71 | 5 | 34,370 | Jimmy Anderson | Steve Parris | Steve Parris | Jimmy Anderson | | 578 | 652 | -74 |
| 2000-08-20 | @ CIN | 122 | W 7-3 | 51-71 | 5 | 32,545 | Jose Silva | Elmer Dessens | Jose Silva | Elmer Dessens | | 585 | 655 | -70 |
| 2000-08-21 | @ SLN | 123 | L 4-7 | 51-72 | 5 | 35,644 | Kris Benson | Garrett Stephenson | Garrett Stephenson | Kris Benson | Dave Veres | 589 | 662 | -73 |
| 2000-08-22 | @ SLN | 124 | W 6-2 | 52-72 | 5 | 31,534 | Dan Serafini | Darryl Kile | Josias Manzanillo | Darryl Kile | | 595 | 664 | -69 |
| 2000-08-23 | @ SLN | 125 | L 2-5 | 52-73 | 5 | 31,288 | Todd Ritchie | Rick Ankiel | Rick Ankiel | Todd Ritchie | Dave Veres | 597 | 669 | -72 |
| 2000-08-25 | vs COL | 126 | L 3-6 | 52-74 | 6 | 23,104 | Jimmy Anderson | Julian Tavarez | Julian Tavarez | Jimmy Anderson | | 600 | 675 | -75 |
| 2000-08-26 | vs COL | 127 | L 4-11 | 52-75 | 6 | 23,340 | Jose Silva | Pedro Astacio | Pedro Astacio | Jose Silva | | 604 | 686 | -82 |
| 2000-08-27 | vs COL | 128 | L 2-9 | 52-76 | 6 | 20,157 | Dan Serafini | Brian Bohanon | Brian Bohanon | Dan Serafini | | 606 | 695 | -89 |
| 2000-08-28 | vs SFN | 129 | L 4-5 | 52-77 | 6 | 15,125 | Todd Ritchie | Shawn Estes | Alan Embree | Scott Sauerbeck | Robb Nen | 610 | 700 | -90 |
| 2000-08-29 | vs SFN | 130 | W 8-0 | 53-77 | 6 | 14,306 | Kris Benson | Livan Hernandez | Kris Benson | Livan Hernandez | | 618 | 700 | -82 |
| 2000-08-30 | vs SFN | 131 | L 0-2 | 53-78 | 6 | 16,576 | Jimmy Anderson | Russ Ortiz | Russ Ortiz | Jimmy Anderson | Robb Nen | 618 | 702 | -84 |
| 2000-08-31 | vs SFN | 132 | L 2-10 | 53-79 | 6 | 13,781 | Jose Silva | Kirk Rueter | Kirk Rueter | Jose Silva | | 620 | 712 | -92 |
| 2000-09-01 | @ SDN | 133 | W 3-2 | 54-79 | 6 | 16,813 | Dan Serafini | Woody Williams | Mike Williams | Trevor Hoffman | | 623 | 714 | -91 |
| 2000-09-02 | @ SDN | 134 | W 6-3 | 55-79 | 6 | 33,358 | Todd Ritchie | Matt Clement | Todd Ritchie | Matt Clement | Scott Sauerbeck | 629 | 717 | -88 |
| 2000-09-03 | @ SDN | 135 | W 8-6 | 56-79 | 6 | 20,389 | Kris Benson | Adam Eaton | Matt Skrmetta | Carlos Almanzar | Mike Williams | 637 | 723 | -86 |
| 2000-09-04 | @ LAN | 136 | W 12-1 | 57-79 | 5 | 31,418 | Jimmy Anderson | Darren Dreifort | Jimmy Anderson | Darren Dreifort | | 649 | 724 | -75 |
| 2000-09-05 | @ LAN | 137 | W 8-0 | 58-79 | 4 | 22,780 | Jose Silva | Carlos Perez | Jose Silva | Carlos Perez | | 657 | 724 | -67 |
| 2000-09-06 | @ LAN | 138 | W 8-3 | 59-79 | 4 | 28,462 | Dan Serafini | Ismael Valdez | Dan Serafini | Ismael Valdez | | 665 | 727 | -62 |
| 2000-09-08 | vs CIN | 139 | W 7-3 | 61-79 | 3 | 0 | Todd Ritchie | Scott Williamson | Todd Ritchie | Scott Williamson | | 672 | 730 | -58 |
| 2000-09-08 | vs CIN | 140 | W 3-1 | 61-79 | 3 | 26,486 | Bronson Arroyo | Ron Villone | Marc Wilkins | Ron Villone | Mike Williams | 675 | 731 | -56 |
| 2000-09-09 | vs CIN | 141 | L 4-6 | 61-80 | 4 | 34,590 | Kris Benson | Steve Parris | Steve Parris | Kris Benson | Danny Graves | 679 | 737 | -58 |
| 2000-09-10 | vs CIN | 142 | L 4-6 | 61-81 | 5 | 35,046 | Jimmy Anderson | Elmer Dessens | Elmer Dessens | Jimmy Anderson | Danny Graves | 683 | 743 | -60 |
| 2000-09-11 | vs SLN | 143 | L 4-8 | 61-82 | 5 | 16,583 | Jose Silva | Garrett Stephenson | Garrett Stephenson | Josias Manzanillo | | 687 | 751 | -64 |
| 2000-09-12 | vs SLN | 144 | L 1-11 | 61-83 | 5 | 15,824 | Dan Serafini | Darryl Kile | Darryl Kile | Dan Serafini | | 688 | 762 | -74 |
| 2000-09-13 | vs SLN | 145 | L 5-9 | 61-84 | 5 | 22,236 | Todd Ritchie | Rick Ankiel | Rick Ankiel | Todd Ritchie | | 693 | 771 | -78 |
| 2000-09-14 | @ HOU | 146 | L 7-8 | 61-85 | 5 | 36,740 | Bronson Arroyo | Chris Holt | Joe Slusarski | Matt Skrmetta | | 700 | 779 | -79 |
| 2000-09-15 | @ HOU | 147 | L 7-16 | 61-86 | 5 | 32,661 | Jimmy Anderson | Tony McKnight | Brian Powell | Matt Skrmetta | Joe Slusarski | 707 | 795 | -88 |
| 2000-09-16 | @ HOU | 148 | L 9-10 | 61-87 | 5 | 41,248 | Jose Silva | Jose Lima | Marc Valdes | Scott Sauerbeck | | 716 | 805 | -89 |
| 2000-09-17 | @ HOU | 149 | L 3-5 | 61-88 | 5 | 40,036 | Dan Serafini | Scott Elarton | Scott Elarton | Dan Serafini | Octavio Dotel | 719 | 810 | -91 |
| 2000-09-18 | @ PHI | 150 | W 6-5 | 62-88 | 5 | 11,470 | Todd Ritchie | Kent Bottenfield | Rich Loiselle | Vicente Padilla | Mike Williams | 725 | 815 | -90 |
| 2000-09-19 | @ PHI | 151 | W 12-8 | 63-88 | 5 | 11,362 | Bronson Arroyo | Bruce Chen | Matt Skrmetta | Amaury Telemaco | Mike Williams | 737 | 823 | -86 |
| 2000-09-20 | @ PHI | 152 | W 7-6 | 64-88 | 5 | 12,762 | Kris Benson | Robert Person | Rich Loiselle | Chris Brock | Mike Williams | 744 | 829 | -85 |
| 2000-09-21 | @ MIL | 153 | L 2-12 | 64-89 | 5 | 14,688 | Jimmy Anderson | Paul Rigdon | Paul Rigdon | Jimmy Anderson | | 746 | 841 | -95 |
| 2000-09-23 | @ MIL | 154 | W 4-2 | 65-90 | 5 | 0 | Jose Silva | Jeff D'Amico | Jose Silva | Jeff D'Amico | Mike Williams | 750 | 843 | -93 |
| 2000-09-23 | @ MIL | 155 | L 4-5 | 65-90 | 5 | 26,040 | Dan Serafini | John Snyder | Curt Leskanic | Bronson Arroyo | | 754 | 848 | -94 |
| 2000-09-24 | @ MIL | 156 | L 5-8 | 65-91 | 5 | 26,186 | Todd Ritchie | Jimmy Haynes | Curt Leskanic | Mike Williams | | 759 | 856 | -97 |
| 2000-09-26 | vs HOU | 157 | W 9-4 | 66-91 | 5 | 14,311 | Kris Benson | Chris Holt | Kris Benson | Chris Holt | | 768 | 860 | -92 |
| 2000-09-27 | vs HOU | 158 | L 1-10 | 66-92 | 5 | 14,511 | Jimmy Anderson | Tony McKnight | Tony McKnight | Jimmy Anderson | | 769 | 870 | -101 |
| 2000-09-28 | vs HOU | 159 | W 3-2 | 67-92 | 5 | 17,710 | Jose Silva | Jose Lima | Jose Silva | Octavio Dotel | | 772 | 872 | -100 |
| 2000-09-29 | vs CHN | 160 | W 8-4 | 68-92 | 5 | 40,128 | Dan Serafini | Jerry Spradlin | Marc Wilkins | Steve Rain | | 780 | 876 | -96 |
| 2000-09-30 | vs CHN | 161 | W 4-2 | 69-92 | 5 | 43,458 | Todd Ritchie | Ruben Quevedo | Todd Ritchie | Ruben Quevedo | Mike Williams | 784 | 878 | -94 |
| 2000-10-01 | vs CHN | 162 | L 9-10 | 69-93 | 5 | 55,351 | Kris Benson | Jon Lieber | Kyle Farnsworth | Scott Sauerbeck | Jamie Arnold | 793 | 888 | -95 |