| 2000-04-03 | @ CIN | 1 | L 3-3 | 0-1 | 5 | 55,596 | Steve Woodard | Pete Harnisch | | | | 3 | 3 | 0 |
| 2000-04-04 | @ CIN | 2 | W 5-1 | 1-1 | 4 | 16,761 | Valerio de los Santos | Denny Neagle | Jim Bruske | Scott Williamson | | 8 | 4 | 4 |
| 2000-04-05 | @ CIN | 3 | W 8-5 | 2-1 | 3 | 23,059 | Jimmy Haynes | Steve Parris | Jimmy Haynes | Steve Parris | Bob Wickman | 16 | 9 | 7 |
| 2000-04-06 | @ CIN | 4 | L 1-5 | 2-2 | 4 | 20,909 | Jaime Navarro | Ron Villone | Ron Villone | Jaime Navarro | | 17 | 14 | 3 |
| 2000-04-07 | @ SLN | 5 | W 9-1 | 3-2 | 2 | 33,089 | Jason Bere | Andy Benes | Jason Bere | Andy Benes | | 26 | 15 | 11 |
| 2000-04-08 | @ SLN | 6 | L 8-10 | 3-3 | 4 | 40,909 | Steve Woodard | Darryl Kile | Darryl Kile | Steve Woodard | Dave Veres | 34 | 25 | 9 |
| 2000-04-09 | @ SLN | 7 | L 2-11 | 3-4 | 4 | 48,082 | Valerio de los Santos | Rick Ankiel | Rick Ankiel | Valerio de los Santos | | 36 | 36 | 0 |
| 2000-04-10 | vs FLO | 8 | W 4-3 | 4-4 | 3 | 53,509 | Jimmy Haynes | Vladimir Nunez | Jimmy Haynes | Vladimir Nunez | Bob Wickman | 40 | 39 | 1 |
| 2000-04-12 | vs FLO | 9 | L 4-11 | 4-5 | 4 | 7,007 | Jaime Navarro | Jesus Sanchez | Jesus Sanchez | Jaime Navarro | | 44 | 50 | -6 |
| 2000-04-13 | vs FLO | 10 | W 4-0 | 5-5 | 3 | 7,023 | Jason Bere | Brad Penny | Jason Bere | Brad Penny | | 48 | 50 | -2 |
| 2000-04-14 | vs ATL | 11 | L 3-6 | 5-6 | 4 | 10,171 | Steve Woodard | Tom Glavine | Tom Glavine | Steve Woodard | Mike Remlinger | 51 | 56 | -5 |
| 2000-04-15 | vs ATL | 12 | W 6-3 | 6-6 | 3 | 24,755 | Jimmy Haynes | Kevin Millwood | David Weathers | John Burkett | Bob Wickman | 57 | 59 | -2 |
| 2000-04-16 | vs ATL | 13 | L 1-2 | 6-7 | 3 | 12,004 | Everett Stull | Terry Mulholland | Terry Mulholland | Everett Stull | Mike Remlinger | 58 | 61 | -3 |
| 2000-04-18 | @ NYN | 14 | L 7-10 | 6-8 | 3 | 17,905 | Jaime Navarro | Mike Hampton | Mike Hampton | Jaime Navarro | Armando Benitez | 65 | 71 | -6 |
| 2000-04-19 | @ NYN | 15 | L 1-3 | 6-9 | 5 | 18,001 | Jason Bere | Rick Reed | Rick Reed | Jason Bere | Armando Benitez | 66 | 74 | -8 |
| 2000-04-20 | @ NYN | 16 | L 4-5 | 6-10 | 6 | 17,002 | Steve Woodard | Al Leiter | Turk Wendell | Curt Leskanic | | 70 | 79 | -9 |
| 2000-04-21 | @ MON | 17 | L 1-5 | 6-11 | 6 | 12,315 | Jimmy Haynes | Dustin Hermanson | Dustin Hermanson | Jimmy Haynes | Ugueth Urbina | 71 | 84 | -13 |
| 2000-04-22 | @ MON | 18 | W 7-3 | 7-11 | 3 | 14,461 | Everett Stull | Hideki Irabu | Everett Stull | Hideki Irabu | | 78 | 87 | -9 |
| 2000-04-23 | @ MON | 19 | L 4-6 | 7-12 | 3 | 14,410 | Jaime Navarro | Javier Vazquez | Javier Vazquez | Jaime Navarro | Ugueth Urbina | 82 | 93 | -11 |
| 2000-04-25 | @ SLN | 20 | L 2-7 | 7-13 | 5 | 28,232 | Jason Bere | Darryl Kile | Darryl Kile | Jason Bere | | 84 | 100 | -16 |
| 2000-04-26 | @ SLN | 21 | L 0-7 | 7-14 | 6 | 29,890 | Steve Woodard | Rick Ankiel | Rick Ankiel | Steve Woodard | | 84 | 107 | -23 |
| 2000-04-27 | @ SLN | 22 | W 8-4 | 8-14 | 5 | 34,572 | Jimmy Haynes | Pat Hentgen | Jimmy Haynes | Pat Hentgen | | 92 | 111 | -19 |
| 2000-04-28 | vs HOU | 23 | L 0-7 | 8-15 | 6 | 15,459 | Jaime Navarro | Chris Holt | Chris Holt | Jaime Navarro | | 92 | 118 | -26 |
| 2000-04-29 | vs HOU | 24 | L 3-10 | 8-16 | 6 | 22,630 | Everett Stull | Scott Elarton | Mike Maddux | Everett Stull | | 95 | 128 | -33 |
| 2000-04-30 | vs HOU | 25 | W 4-3 | 9-16 | 6 | 19,647 | Jason Bere | Shane Reynolds | David Weathers | Doug Henry | | 99 | 131 | -32 |
| 2000-05-01 | vs HOU | 26 | L 0-5 | 9-17 | 6 | 7,247 | Steve Woodard | Octavio Dotel | Octavio Dotel | Steve Woodard | | 99 | 136 | -37 |
| 2000-05-02 | vs ARI | 27 | L 1-5 | 9-18 | 6 | 8,281 | Jimmy Haynes | Todd Stottlemyre | Todd Stottlemyre | Jimmy Haynes | | 100 | 141 | -41 |
| 2000-05-03 | vs ARI | 28 | W 4-1 | 10-18 | 6 | 9,600 | Horacio Estrada | Omar Daal | Horacio Estrada | Omar Daal | Bob Wickman | 104 | 142 | -38 |
| 2000-05-04 | vs ARI | 29 | L 2-6 | 10-19 | 6 | 8,405 | Everett Stull | Armando Reynoso | Armando Reynoso | Everett Stull | Byung-Hyun Kim | 106 | 148 | -42 |
| 2000-05-05 | vs MON | 30 | L 2-10 | 10-20 | 6 | 10,002 | Jason Bere | Javier Vazquez | Javier Vazquez | Jason Bere | | 108 | 158 | -50 |
| 2000-05-06 | vs MON | 31 | L 2-3 | 10-21 | 6 | 12,381 | Steve Woodard | Carl Pavano | Anthony Telford | David Weathers | Ugueth Urbina | 110 | 161 | -51 |
| 2000-05-07 | vs MON | 32 | W 9-4 | 11-21 | 6 | 11,989 | Jimmy Haynes | Dustin Hermanson | Jimmy Haynes | Dustin Hermanson | | 119 | 165 | -46 |
| 2000-05-08 | @ CHN | 33 | L 11-12 | 11-22 | 6 | 29,135 | Horacio Estrada | Jon Lieber | Felix Heredia | Bob Wickman | | 130 | 177 | -47 |
| 2000-05-09 | @ CHN | 34 | W 4-3 | 12-22 | 6 | 29,657 | Jeff D'Amico | Ismael Valdez | Jeff D'Amico | Mark Guthrie | David Weathers | 134 | 180 | -46 |
| 2000-05-10 | @ CHN | 35 | L 8-9 | 12-23 | 6 | 24,601 | Jason Bere | Kevin Tapani | Rick Aguilera | Valerio de los Santos | | 142 | 189 | -47 |
| 2000-05-11 | @ CHN | 36 | W 14-8 | 13-23 | 6 | 21,995 | Steve Woodard | Scott Downs | Steve Woodard | Brian Williams | | 156 | 197 | -41 |
| 2000-05-12 | @ PIT | 37 | W 6-1 | 14-23 | 5 | 18,524 | Jimmy Haynes | Jason Schmidt | Jimmy Haynes | Jason Schmidt | | 162 | 198 | -36 |
| 2000-05-13 | @ PIT | 38 | L 8-11 | 14-24 | 6 | 26,682 | Horacio Estrada | Brian O'Connor | Scott Sauerbeck | Juan Acevedo | Mike Williams | 170 | 209 | -39 |
| 2000-05-14 | @ PIT | 39 | L 0-3 | 14-25 | 6 | 19,657 | Jeff D'Amico | Kris Benson | Kris Benson | Jeff D'Amico | Jason Christiansen | 170 | 212 | -42 |
| 2000-05-16 | vs HOU | 40 | W 6-5 | 15-25 | 5 | 9,239 | Jason Bere | Shane Reynolds | Horacio Estrada | Chris Holt | | 176 | 217 | -41 |
| 2000-05-19 | vs SFN | 41 | W 11-10 | 16-25 | 4 | 12,842 | Jimmy Haynes | Livan Hernandez | Bob Wickman | Robb Nen | | 187 | 227 | -40 |
| 2000-05-20 | vs SFN | 42 | W 7-0 | 17-25 | 4 | 15,712 | Jeff D'Amico | Mark Gardner | Jeff D'Amico | Mark Gardner | | 194 | 227 | -33 |
| 2000-05-21 | vs SFN | 43 | L 10-16 | 17-26 | 4 | 20,571 | John Snyder | Russ Ortiz | Russ Ortiz | Hector Ramirez | | 204 | 243 | -39 |
| 2000-05-22 | vs HOU | 44 | W 10-9 | 19-26 | 4 | 0 | Steve Woodard | Shane Reynolds | David Weathers | Joe Slusarski | | 214 | 252 | -38 |
| 2000-05-22 | vs HOU | 45 | W 6-1 | 19-26 | 4 | 3,913 | Jason Bere | Kip Gross | Jason Bere | Kip Gross | | 220 | 253 | -33 |
| 2000-05-23 | vs ATL | 46 | W 7-6 | 20-26 | 4 | 15,808 | Jamey Wright | Kevin Millwood | Jamey Wright | Kevin Millwood | Bob Wickman | 227 | 259 | -32 |
| 2000-05-24 | vs ATL | 47 | L 2-11 | 20-27 | 4 | 18,153 | Jimmy Haynes | Greg Maddux | Greg Maddux | Jimmy Haynes | | 229 | 270 | -41 |
| 2000-05-25 | vs ATL | 48 | L 3-7 | 20-28 | 4 | 21,527 | Jeff D'Amico | Terry Mulholland | Terry Mulholland | Jeff D'Amico | | 232 | 277 | -45 |
| 2000-05-26 | @ ARI | 49 | L 2-9 | 20-29 | 4 | 34,846 | John Snyder | Randy Johnson | Randy Johnson | John Snyder | | 234 | 286 | -52 |
| 2000-05-27 | @ ARI | 50 | L 3-7 | 20-30 | 4 | 35,163 | Jason Bere | Armando Reynoso | Armando Reynoso | Juan Acevedo | Byung-Hyun Kim | 237 | 293 | -56 |
| 2000-05-28 | @ ARI | 51 | W 4-3 | 21-30 | 4 | 35,121 | Jamey Wright | Brian Anderson | Bob Wickman | Greg Swindell | | 241 | 296 | -55 |
| 2000-05-29 | @ SDN | 52 | W 8-3 | 22-30 | 4 | 16,863 | Jimmy Haynes | Brian Meadows | Jimmy Haynes | Brian Meadows | | 249 | 299 | -50 |
| 2000-05-30 | @ SDN | 53 | L 3-6 | 22-31 | 4 | 15,379 | Jeff D'Amico | Adam Eaton | Adam Eaton | Jeff D'Amico | Trevor Hoffman | 252 | 305 | -53 |
| 2000-05-31 | @ SDN | 54 | L 5-9 | 22-32 | 4 | 14,784 | John Snyder | Rodrigo Lopez | Carlos Almanzar | David Weathers | | 257 | 314 | -57 |
| 2000-06-02 | vs COL | 55 | L 6-8 | 22-33 | 5 | 14,110 | Jason Bere | Rolando Arrojo | Rolando Arrojo | Jason Bere | Mike Myers | 263 | 322 | -59 |
| 2000-06-03 | vs COL | 56 | W 2-1 | 23-33 | 4 | 20,730 | Jamey Wright | Pedro Astacio | Valerio de los Santos | Stan Belinda | | 265 | 323 | -58 |
| 2000-06-04 | vs COL | 57 | L 1-7 | 23-34 | 4 | 17,147 | Jimmy Haynes | Kevin Jarvis | Kevin Jarvis | Jimmy Haynes | | 266 | 330 | -64 |
| 2000-06-05 | vs CLE | 58 | L 4-8 | 23-35 | 5 | 13,749 | Jeff D'Amico | Dave Burba | Dave Burba | Jeff D'Amico | | 270 | 338 | -68 |
| 2000-06-06 | vs CLE | 59 | L 2-4 | 23-36 | 5 | 24,595 | John Snyder | Chuck Finley | Chuck Finley | John Snyder | | 272 | 342 | -70 |
| 2000-06-07 | vs CLE | 60 | L 5-9 | 23-37 | 5 | 15,518 | Jason Bere | Paul Rigdon | Jamie Brewington | Jason Bere | | 277 | 351 | -74 |
| 2000-06-09 | @ MIN | 61 | L 6-9 | 23-38 | 5 | 20,258 | Jamey Wright | Sean Bergman | Sean Bergman | Jamey Wright | | 283 | 360 | -77 |
| 2000-06-10 | @ MIN | 62 | W 5-3 | 24-38 | 5 | 17,023 | Jimmy Haynes | Mark Redman | Jimmy Haynes | Mark Redman | Bob Wickman | 288 | 363 | -75 |
| 2000-06-11 | @ MIN | 63 | W 5-3 | 25-38 | 5 | 11,715 | John Snyder | Brad Radke | John Snyder | Brad Radke | Bob Wickman | 293 | 366 | -73 |
| 2000-06-12 | vs MON | 64 | W 8-1 | 26-38 | 5 | 16,686 | Jason Bere | Javier Vazquez | Jason Bere | Javier Vazquez | | 301 | 367 | -66 |
| 2000-06-13 | vs MON | 65 | L 4-9 | 26-39 | 5 | 10,705 | Steve Woodard | Carl Pavano | Carl Pavano | Steve Woodard | | 305 | 376 | -71 |
| 2000-06-14 | vs MON | 66 | W 11-2 | 27-39 | 5 | 12,875 | Jamey Wright | Mike Johnson | Jamey Wright | Mike Johnson | | 316 | 378 | -62 |
| 2000-06-16 | vs NYN | 67 | L 1-7 | 27-40 | 5 | 18,979 | Jimmy Haynes | Al Leiter | Al Leiter | Jimmy Haynes | | 317 | 385 | -68 |
| 2000-06-17 | vs NYN | 68 | W 3-2 | 28-40 | 5 | 26,125 | John Snyder | Glendon Rusch | John Snyder | Glendon Rusch | Bob Wickman | 320 | 387 | -67 |
| 2000-06-18 | vs NYN | 69 | L 3-7 | 28-41 | 5 | 20,133 | Jason Bere | Rick Reed | Rick Reed | Jason Bere | | 323 | 394 | -71 |
| 2000-06-19 | @ FLO | 70 | W 2-0 | 29-41 | 5 | 7,612 | Jamey Wright | Chuck Smith | Jamey Wright | Chuck Smith | Bob Wickman | 325 | 394 | -69 |
| 2000-06-20 | @ FLO | 71 | L 2-8 | 29-42 | 5 | 7,743 | Steve Woodard | Ryan Dempster | Ryan Dempster | Steve Woodard | | 327 | 402 | -75 |
| 2000-06-21 | @ FLO | 72 | L 4-5 | 29-43 | 5 | 8,070 | Jimmy Haynes | Reid Cornelius | Braden Looper | Jimmy Haynes | Antonio Alfonseca | 331 | 407 | -76 |
| 2000-06-22 | @ FLO | 73 | W 6-1 | 30-43 | 5 | 8,285 | John Snyder | Jesus Sanchez | John Snyder | Jesus Sanchez | | 337 | 408 | -71 |
| 2000-06-23 | @ ATL | 74 | L 2-3 | 30-44 | 5 | 41,402 | Jason Bere | John Burkett | Jason Marquis | David Weathers | John Rocker | 339 | 411 | -72 |
| 2000-06-24 | @ ATL | 75 | W 2-1 | 31-44 | 4 | 49,802 | Jamey Wright | Greg Maddux | Jamey Wright | Greg Maddux | Bob Wickman | 341 | 412 | -71 |
| 2000-06-25 | @ ATL | 76 | L 4-5 | 31-45 | 4 | 40,268 | Allen Levrault | Kevin Millwood | John Rocker | Curt Leskanic | | 345 | 417 | -72 |
| 2000-06-27 | @ PHI | 77 | L 0-7 | 31-46 | 4 | 15,256 | Jimmy Haynes | Curt Schilling | Curt Schilling | Jimmy Haynes | | 345 | 424 | -79 |
| 2000-06-28 | @ PHI | 78 | L 7-9 | 31-47 | 5 | 13,520 | John Snyder | Andy Ashby | Chris Brock | Juan Acevedo | Jeff Brantley | 352 | 433 | -81 |
| 2000-06-29 | @ PHI | 79 | W 8-6 | 32-47 | 4 | 21,597 | Jason Bere | Dave Coggin | Jason Bere | Steve Schrenk | Curt Leskanic | 360 | 439 | -79 |
| 2000-06-30 | vs CHN | 80 | L 4-7 | 32-48 | 5 | 30,216 | Jamey Wright | Scott Downs | Daniel Garibay | Allen Levrault | Rick Aguilera | 364 | 446 | -82 |
| 2000-07-01 | vs CHN | 81 | W 4-0 | 33-48 | 4 | 37,176 | Jeff D'Amico | Ismael Valdez | Jeff D'Amico | Ismael Valdez | | 368 | 446 | -78 |
| 2000-07-02 | vs CHN | 82 | W 4-2 | 34-48 | 4 | 37,659 | Jimmy Haynes | Kerry Wood | Jimmy Haynes | Kerry Wood | Bob Wickman | 372 | 448 | -76 |
| 2000-07-03 | vs PHI | 83 | L 3-5 | 34-49 | 4 | 13,903 | John Snyder | Andy Ashby | Andy Ashby | John Snyder | Jeff Brantley | 375 | 453 | -78 |
| 2000-07-04 | vs PHI | 84 | L 4-7 | 34-50 | 4 | 14,602 | Jason Bere | Dave Coggin | Chris Brock | Bob Wickman | Jeff Brantley | 379 | 460 | -81 |
| 2000-07-05 | vs PHI | 85 | L 2-5 | 34-51 | 4 | 10,677 | Jamey Wright | Randy Wolf | Randy Wolf | Jamey Wright | Wayne Gomes | 381 | 465 | -84 |
| 2000-07-06 | vs PHI | 86 | W 4-2 | 35-51 | 4 | 12,578 | Jeff D'Amico | Paul Byrd | Jeff D'Amico | Paul Byrd | Bob Wickman | 385 | 467 | -82 |
| 2000-07-07 | vs DET | 87 | W 4-3 | 36-51 | 4 | 13,913 | Jimmy Haynes | Brian Moehler | Jimmy Haynes | Brian Moehler | Bob Wickman | 389 | 470 | -81 |
| 2000-07-08 | vs DET | 88 | L 2-4 | 36-52 | 4 | 23,872 | John Snyder | Hideo Nomo | Nelson Cruz | Valerio de los Santos | | 391 | 474 | -83 |
| 2000-07-09 | vs DET | 89 | W 10-3 | 37-52 | 4 | 19,037 | Jason Bere | Willie Blair | Jason Bere | Willie Blair | | 401 | 477 | -76 |
| 2000-07-13 | @ KCA | 90 | W 5-2 | 38-52 | 4 | 18,525 | Jamey Wright | Blake Stein | Jamey Wright | Blake Stein | Bob Wickman | 406 | 479 | -73 |
| 2000-07-14 | @ KCA | 91 | W 4-0 | 39-52 | 4 | 29,473 | Jeff D'Amico | Mac Suzuki | Jeff D'Amico | Mac Suzuki | | 410 | 479 | -69 |
| 2000-07-15 | @ KCA | 92 | L 4-7 | 39-53 | 4 | 23,598 | Jimmy Haynes | Jeff Suppan | Jeff Suppan | Jimmy Haynes | Ricky Bottalico | 414 | 486 | -72 |
| 2000-07-16 | @ CHA | 93 | L 5-11 | 39-54 | 5 | 30,050 | John Snyder | James Baldwin | James Baldwin | John Snyder | | 419 | 497 | -78 |
| 2000-07-17 | @ CHA | 94 | L 2-11 | 39-55 | 5 | 31,369 | Jason Bere | Jon Garland | Jon Garland | Jason Bere | | 421 | 508 | -87 |
| 2000-07-18 | @ CHA | 95 | L 5-7 | 39-56 | 5 | 18,542 | Jamey Wright | Mike Sirotka | Mike Sirotka | Jamey Wright | Kelly Wunsch | 426 | 515 | -89 |
| 2000-07-19 | vs PIT | 96 | W 6-0 | 40-56 | 5 | 20,840 | Jeff D'Amico | Kris Benson | Jeff D'Amico | Kris Benson | | 432 | 515 | -83 |
| 2000-07-20 | vs PIT | 97 | L 2-9 | 40-57 | 5 | 29,389 | Jimmy Haynes | Jose Silva | Jose Silva | Jimmy Haynes | | 434 | 524 | -90 |
| 2000-07-21 | @ CHN | 98 | L 2-4 | 40-58 | 5 | 38,991 | John Snyder | Kerry Wood | Kerry Wood | John Snyder | Rick Aguilera | 436 | 528 | -92 |
| 2000-07-22 | @ CHN | 99 | L 2-3 | 40-59 | 5 | 39,464 | Jason Bere | Scott Downs | Felix Heredia | Steve Woodard | | 438 | 531 | -93 |
| 2000-07-23 | @ CHN | 100 | L 4-5 | 40-60 | 5 | 38,678 | Jamey Wright | Ismael Valdez | Ismael Valdez | Jamey Wright | Rick Aguilera | 442 | 536 | -94 |
| 2000-07-25 | @ PIT | 101 | W 4-1 | 41-60 | 5 | 15,808 | Jeff D'Amico | Kris Benson | Curt Leskanic | Jason Christiansen | Bob Wickman | 446 | 537 | -91 |
| 2000-07-26 | @ PIT | 102 | L 4-5 | 41-61 | 5 | 20,421 | Jimmy Haynes | Jose Silva | Jose Silva | Jimmy Haynes | Mike Williams | 450 | 542 | -92 |
| 2000-07-27 | @ PIT | 103 | W 4-3 | 42-61 | 5 | 16,636 | John Snyder | Jimmy Anderson | Curt Leskanic | Josias Manzanillo | Bob Wickman | 454 | 545 | -91 |
| 2000-07-28 | vs COL | 104 | W 5-0 | 43-61 | 5 | 21,239 | Jamey Wright | Pedro Astacio | Jamey Wright | Pedro Astacio | | 459 | 545 | -86 |
| 2000-07-29 | vs COL | 105 | L 2-10 | 43-62 | 5 | 21,762 | Paul Rigdon | Julian Tavarez | Julian Tavarez | Paul Rigdon | | 461 | 555 | -94 |
| 2000-07-30 | vs COL | 106 | W 3-2 | 44-62 | 5 | 21,071 | Jeff D'Amico | Masato Yoshii | Jeff D'Amico | Masato Yoshii | Curt Leskanic | 464 | 557 | -93 |
| 2000-07-31 | vs SFN | 107 | L 3-4 | 44-63 | 5 | 20,530 | Jimmy Haynes | Mark Gardner | Felix Rodriguez | David Weathers | Robb Nen | 467 | 561 | -94 |
| 2000-08-01 | vs SFN | 108 | L 8-13 | 44-64 | 5 | 15,722 | John Snyder | Shawn Estes | Doug Henry | Ray King | | 475 | 574 | -99 |
| 2000-08-02 | vs SFN | 109 | W 6-4 | 45-64 | 5 | 25,753 | Jamey Wright | Livan Hernandez | Juan Acevedo | Livan Hernandez | Curt Leskanic | 481 | 578 | -97 |
| 2000-08-04 | @ LAN | 110 | L 1-2 | 45-65 | 5 | 36,074 | Paul Rigdon | Kevin Brown | Mike Fetters | Juan Acevedo | | 482 | 580 | -98 |
| 2000-08-05 | @ LAN | 111 | W 4-2 | 46-65 | 5 | 42,580 | Jeff D'Amico | Chan Ho Park | Juan Acevedo | Mike Fetters | Curt Leskanic | 486 | 582 | -96 |
| 2000-08-06 | @ LAN | 112 | W 9-6 | 47-65 | 5 | 40,275 | Jimmy Haynes | Ismael Valdez | Jimmy Haynes | Ismael Valdez | Curt Leskanic | 495 | 588 | -93 |
| 2000-08-07 | @ SFN | 113 | L 1-8 | 47-66 | 5 | 40,930 | John Snyder | Livan Hernandez | Livan Hernandez | John Snyder | | 496 | 596 | -100 |
| 2000-08-08 | @ SFN | 114 | L 0-1 | 47-67 | 5 | 40,930 | Jamey Wright | Russ Ortiz | Russ Ortiz | Jamey Wright | Robb Nen | 496 | 597 | -101 |
| 2000-08-09 | @ SFN | 115 | L 3-9 | 47-68 | 5 | 40,930 | Paul Rigdon | Kirk Rueter | Kirk Rueter | Paul Rigdon | | 499 | 606 | -107 |
| 2000-08-11 | vs SLN | 116 | W 6-2 | 48-68 | 5 | 25,890 | Jeff D'Amico | Darryl Kile | Jeff D'Amico | Darryl Kile | | 505 | 608 | -103 |
| 2000-08-12 | vs SLN | 117 | L 1-2 | 48-69 | 5 | 31,502 | Jimmy Haynes | Rick Ankiel | Matt Morris | Curt Leskanic | Mike James | 506 | 610 | -104 |
| 2000-08-13 | vs SLN | 118 | L 4-6 | 48-70 | 5 | 33,496 | Jamey Wright | Pat Hentgen | Pat Hentgen | Jamey Wright | Dave Veres | 510 | 616 | -106 |
| 2000-08-14 | vs CIN | 119 | W 4-3 | 49-70 | 5 | 25,853 | Paul Rigdon | Elmer Dessens | Paul Rigdon | Elmer Dessens | Curt Leskanic | 514 | 619 | -105 |
| 2000-08-15 | vs CIN | 120 | W 2-1 | 50-70 | 4 | 19,649 | John Snyder | Pete Harnisch | Curt Leskanic | Mark Wohlers | | 516 | 620 | -104 |
| 2000-08-16 | vs CIN | 121 | W 5-1 | 51-70 | 4 | 26,339 | Jeff D'Amico | Rob Bell | Jeff D'Amico | Rob Bell | | 521 | 621 | -100 |
| 2000-08-18 | @ HOU | 122 | L 4-5 | 51-71 | 4 | 36,781 | Jimmy Haynes | Wade Miller | Wade Miller | Jimmy Haynes | Octavio Dotel | 525 | 626 | -101 |
| 2000-08-19 | @ HOU | 123 | L 8-10 | 51-72 | 4 | 42,297 | Jamey Wright | Chris Holt | Jose Cabrera | Juan Acevedo | Octavio Dotel | 533 | 636 | -103 |
| 2000-08-20 | @ HOU | 124 | W 6-5 | 52-72 | 4 | 35,592 | Paul Rigdon | Jose Lima | Curt Leskanic | Jose Cabrera | | 539 | 641 | -102 |
| 2000-08-21 | @ ARI | 125 | W 16-8 | 53-72 | 4 | 31,752 | John Snyder | Armando Reynoso | Everett Stull | Armando Reynoso | | 555 | 649 | -94 |
| 2000-08-22 | @ ARI | 126 | W 4-3 | 54-72 | 4 | 31,057 | Jeff D'Amico | Geraldo Guzman | Jeff D'Amico | Geraldo Guzman | Curt Leskanic | 559 | 652 | -93 |
| 2000-08-23 | @ ARI | 127 | W 8-5 | 55-72 | 4 | 29,954 | Jimmy Haynes | Curt Schilling | Jimmy Haynes | Curt Schilling | Curt Leskanic | 567 | 657 | -90 |
| 2000-08-25 | vs SDN | 128 | L 0-4 | 55-73 | 4 | 20,389 | Jamey Wright | Brian Tollberg | Brian Tollberg | Jamey Wright | | 567 | 661 | -94 |
| 2000-08-26 | vs SDN | 129 | W 6-5 | 56-73 | 4 | 20,240 | Paul Rigdon | Jay Witasick | Curt Leskanic | Trevor Hoffman | | 573 | 666 | -93 |
| 2000-08-27 | vs SDN | 130 | L 1-2 | 56-74 | 4 | 21,785 | John Snyder | Woody Williams | Woody Williams | David Weathers | Trevor Hoffman | 574 | 668 | -94 |
| 2000-08-28 | vs LAN | 131 | L 3-5 | 56-75 | 4 | 17,167 | Jeff D'Amico | Kevin Brown | Kevin Brown | Jeff D'Amico | Jeff Shaw | 577 | 673 | -96 |
| 2000-08-29 | vs LAN | 132 | L 2-7 | 56-76 | 4 | 14,179 | Jimmy Haynes | Chan Ho Park | Chan Ho Park | Jimmy Haynes | | 579 | 680 | -101 |
| 2000-08-30 | vs LAN | 133 | W 3-2 | 57-76 | 4 | 15,940 | Jamey Wright | Darren Dreifort | Ray King | Terry Adams | | 582 | 682 | -100 |
| 2000-08-31 | vs LAN | 134 | W 8-2 | 58-76 | 4 | 15,483 | Paul Rigdon | Carlos Perez | Paul Rigdon | Carlos Perez | | 590 | 684 | -94 |
| 2000-09-01 | @ COL | 135 | L 3-5 | 58-77 | 4 | 38,970 | John Snyder | Pedro Astacio | Pedro Astacio | John Snyder | Gabe White | 593 | 689 | -96 |
| 2000-09-02 | @ COL | 136 | W 8-3 | 59-77 | 3 | 36,139 | Jeff D'Amico | Brian Bohanon | Jeff D'Amico | Mike DeJean | | 601 | 692 | -91 |
| 2000-09-03 | @ COL | 137 | W 6-4 | 60-77 | 3 | 36,576 | Jimmy Haynes | Masato Yoshii | Juan Acevedo | Mike DeJean | Curt Leskanic | 607 | 696 | -89 |
| 2000-09-04 | @ SDN | 138 | L 3-4 | 60-78 | 3 | 15,183 | Jamey Wright | Brian Tollberg | Tom Davey | Ray King | Trevor Hoffman | 610 | 700 | -90 |
| 2000-09-05 | @ SDN | 139 | L 1-3 | 60-79 | 3 | 14,001 | Paul Rigdon | Jay Witasick | Jay Witasick | Paul Rigdon | Trevor Hoffman | 611 | 703 | -92 |
| 2000-09-06 | @ SDN | 140 | L 6-7 | 60-80 | 3 | 13,777 | John Snyder | Woody Williams | Woody Williams | John Snyder | Trevor Hoffman | 617 | 710 | -93 |
| 2000-09-08 | vs SLN | 141 | W 6-5 | 61-80 | 5 | 21,664 | Jeff D'Amico | Rick Ankiel | Curt Leskanic | Dave Veres | | 623 | 715 | -92 |
| 2000-09-09 | vs SLN | 142 | L 6-7 | 61-81 | 5 | 25,095 | Jimmy Haynes | Pat Hentgen | Dave Veres | Juan Acevedo | | 629 | 722 | -93 |
| 2000-09-10 | vs SLN | 143 | W 4-3 | 62-81 | 4 | 31,528 | Jamey Wright | Britt Reames | Ray King | Andy Benes | | 633 | 725 | -92 |
| 2000-09-11 | @ NYN | 144 | W 8-2 | 63-81 | 4 | 21,797 | Paul Rigdon | Rick Reed | Paul Rigdon | Rick Reed | | 641 | 727 | -86 |
| 2000-09-12 | @ NYN | 145 | L 2-10 | 63-82 | 4 | 22,570 | John Snyder | Robert Joseph Jones | Robert Joseph Jones | John Snyder | | 643 | 737 | -94 |
| 2000-09-13 | @ NYN | 146 | L 1-4 | 63-83 | 4 | 22,510 | Jeff D'Amico | Mike Hampton | Armando Benitez | Juan Acevedo | | 644 | 741 | -97 |
| 2000-09-14 | @ CIN | 147 | W 6-4 | 64-83 | 4 | 19,472 | Jimmy Haynes | Ron Villone | Jimmy Haynes | Ron Villone | Curt Leskanic | 650 | 745 | -95 |
| 2000-09-15 | @ CIN | 148 | L 4-6 | 64-84 | 4 | 24,354 | Jamey Wright | Steve Parris | Steve Parris | Jamey Wright | Danny Graves | 654 | 751 | -97 |
| 2000-09-16 | @ CIN | 149 | L 3-7 | 64-85 | 4 | 29,350 | Paul Rigdon | Elmer Dessens | Elmer Dessens | Paul Rigdon | John Riedling | 657 | 758 | -101 |
| 2000-09-17 | @ CIN | 150 | L 4-8 | 64-86 | 4 | 26,299 | John Snyder | Pete Harnisch | Pete Harnisch | John Snyder | | 661 | 766 | -105 |
| 2000-09-18 | vs CHN | 151 | W 2-1 | 65-86 | 4 | 21,367 | Jeff D'Amico | Todd Van Poppel | Jeff D'Amico | Todd Van Poppel | Curt Leskanic | 663 | 767 | -104 |
| 2000-09-19 | vs CHN | 152 | W 9-8 | 66-86 | 4 | 24,374 | Jimmy Haynes | Ruben Quevedo | Ray King | Kyle Farnsworth | | 672 | 775 | -103 |
| 2000-09-20 | vs CHN | 153 | W 3-2 | 67-86 | 4 | 24,134 | Jamey Wright | Jon Lieber | Curt Leskanic | Kyle Farnsworth | | 675 | 777 | -102 |
| 2000-09-21 | vs PIT | 154 | W 12-2 | 68-86 | 4 | 14,688 | Paul Rigdon | Jimmy Anderson | Paul Rigdon | Jimmy Anderson | | 687 | 779 | -92 |
| 2000-09-23 | vs PIT | 155 | L 2-4 | 69-87 | 4 | 0 | Jeff D'Amico | Jose Silva | Jose Silva | Jeff D'Amico | Mike Williams | 689 | 783 | -94 |
| 2000-09-23 | vs PIT | 156 | W 5-4 | 69-87 | 4 | 26,040 | John Snyder | Dan Serafini | Curt Leskanic | Bronson Arroyo | | 694 | 787 | -93 |
| 2000-09-24 | vs PIT | 157 | W 8-5 | 70-87 | 3 | 26,186 | Jimmy Haynes | Todd Ritchie | Curt Leskanic | Mike Williams | | 702 | 792 | -90 |
| 2000-09-26 | vs CIN | 158 | W 7-4 | 71-87 | 3 | 27,851 | Jamey Wright | Steve Parris | Jamey Wright | Steve Parris | Curt Leskanic | 709 | 796 | -87 |
| 2000-09-27 | vs CIN | 159 | W 10-6 | 72-87 | 3 | 27,262 | Paul Rigdon | Rob Bell | Valerio de los Santos | John Riedling | | 719 | 802 | -83 |
| 2000-09-28 | vs CIN | 160 | L 1-8 | 72-88 | 3 | 56,354 | Jeff D'Amico | Elmer Dessens | Elmer Dessens | Jeff D'Amico | | 720 | 810 | -90 |
| 2000-09-29 | @ HOU | 161 | W 13-3 | 73-88 | 3 | 37,943 | Horacio Estrada | Scott Elarton | Horacio Estrada | Scott Elarton | | 733 | 813 | -80 |
| 2000-09-30 | @ HOU | 162 | L 6-7 | 73-89 | 3 | 42,161 | Jimmy Haynes | Wade Miller | Wade Miller | Jimmy Haynes | Octavio Dotel | 739 | 820 | -81 |
| 2000-10-01 | @ HOU | 163 | L 1-6 | 73-90 | 3 | 35,558 | Jamey Wright | Chris Holt | Chris Holt | Jamey Wright | | 740 | 826 | -86 |