| 2000-04-03 | vs NYA | 1 | L 2-3 | 0-1 | 2 | 42,704 | Ken Hill | Orlando Hernandez | Orlando Hernandez | Ken Hill | Mariano Rivera | 2 | 3 | -1 |
| 2000-04-04 | vs NYA | 2 | L 3-5 | 0-2 | 3 | 25,818 | Kent Bottenfield | Roger Clemens | Ramiro Mendoza | Troy Percival | Mariano Rivera | 5 | 8 | -3 |
| 2000-04-05 | vs NYA | 3 | W 12-6 | 1-2 | 4 | 24,560 | Scott Schoeneweis | David Cone | Scott Schoeneweis | David Cone | | 17 | 14 | 3 |
| 2000-04-07 | vs BOS | 4 | W 7-3 | 2-2 | 3 | 30,412 | Jason Dickson | Pete Schourek | Jason Dickson | Pete Schourek | | 24 | 17 | 7 |
| 2000-04-08 | vs BOS | 5 | W 7-5 | 3-2 | 1 | 27,369 | Ken Hill | Brian Rose | Ken Hill | Brian Rose | Troy Percival | 31 | 22 | 9 |
| 2000-04-09 | vs BOS | 6 | L 2-5 | 3-3 | 3 | 35,847 | Kent Bottenfield | Pedro Martinez | Pedro Martinez | Kent Bottenfield | | 33 | 27 | 6 |
| 2000-04-10 | vs TOR | 7 | W 6-0 | 4-3 | 2 | 14,338 | Scott Schoeneweis | Chris Carpenter | Scott Schoeneweis | Chris Carpenter | | 39 | 27 | 12 |
| 2000-04-11 | vs TOR | 8 | W 5-4 | 5-3 | 1 | 15,229 | Ramon Ortiz | Kelvim Escobar | Ramon Ortiz | Kelvim Escobar | Troy Percival | 44 | 31 | 13 |
| 2000-04-12 | vs TOR | 9 | L 2-6 | 5-4 | 2 | 16,494 | Jason Dickson | Frank Castillo | Pedro Borbon | Mark Petkovsek | | 46 | 37 | 9 |
| 2000-04-14 | @ CHA | 10 | L 4-9 | 5-5 | 2 | 38,912 | Ken Hill | Mike Sirotka | Mike Sirotka | Ken Hill | | 50 | 46 | 4 |
| 2000-04-15 | @ CHA | 11 | W 3-1 | 6-5 | 2 | 14,135 | Kent Bottenfield | Kip Wells | Kent Bottenfield | Kip Wells | Troy Percival | 53 | 47 | 6 |
| 2000-04-16 | @ CHA | 12 | W 3-1 | 7-5 | 2 | 10,929 | Scott Schoeneweis | Jim Parque | Scott Schoeneweis | Jim Parque | Troy Percival | 56 | 48 | 8 |
| 2000-04-17 | @ TOR | 13 | L 1-7 | 7-6 | 2 | 13,622 | Ramon Ortiz | Kelvim Escobar | Kelvim Escobar | Ramon Ortiz | | 57 | 55 | 2 |
| 2000-04-18 | @ TOR | 14 | W 16-10 | 8-6 | 2 | 13,825 | Jason Dickson | Frank Castillo | Jason Dickson | Frank Castillo | | 73 | 65 | 8 |
| 2000-04-19 | @ TOR | 15 | L 4-12 | 8-7 | 2 | 13,572 | Ken Hill | David Wells | David Wells | Ken Hill | | 77 | 77 | 0 |
| 2000-04-20 | @ TOR | 16 | L 11-12 | 8-8 | 2 | 13,985 | Kent Bottenfield | Roy Halladay | Roy Halladay | Kent Bottenfield | Billy Koch | 88 | 89 | -1 |
| 2000-04-21 | @ TBA | 17 | W 9-6 | 9-8 | 2 | 22,221 | Scott Schoeneweis | Dwight Gooden | Mark Petkovsek | Roberto Hernandez | Troy Percival | 97 | 95 | 2 |
| 2000-04-22 | @ TBA | 18 | L 9-11 | 9-9 | 2 | 22,042 | Ramon Ortiz | Esteban Yan | Albie Lopez | Kent Mercker | | 106 | 106 | 0 |
| 2000-04-23 | @ TBA | 19 | L 0-1 | 9-10 | 2 | 15,601 | Jason Dickson | Dave Eiland | Dave Eiland | Jason Dickson | Roberto Hernandez | 106 | 107 | -1 |
| 2000-04-24 | vs DET | 20 | W 10-4 | 10-10 | 2 | 16,433 | Ken Hill | Dave Mlicki | Ken Hill | Dave Mlicki | | 116 | 111 | 5 |
| 2000-04-25 | vs DET | 21 | L 2-4 | 10-11 | 2 | 17,086 | Kent Bottenfield | Hideo Nomo | Jim Poole | Kent Bottenfield | Todd Jones | 118 | 115 | 3 |
| 2000-04-26 | vs DET | 22 | W 6-1 | 11-11 | 2 | 16,153 | Scott Schoeneweis | C.J. Nitkowski | Scott Schoeneweis | C.J. Nitkowski | | 124 | 116 | 8 |
| 2000-04-27 | vs TBA | 23 | L 3-7 | 11-12 | 2 | 16,144 | Ramon Ortiz | Dwight Gooden | Dwight Gooden | Ramon Ortiz | | 127 | 123 | 4 |
| 2000-04-28 | vs TBA | 24 | L 2-11 | 11-13 | 2 | 31,888 | Jason Dickson | Esteban Yan | Esteban Yan | Jason Dickson | | 129 | 134 | -5 |
| 2000-04-29 | vs TBA | 25 | W 7-6 | 12-13 | 2 | 26,827 | Ken Hill | Dave Eiland | Al Levine | Jeff Sparks | | 136 | 140 | -4 |
| 2000-04-30 | vs TBA | 26 | W 5-2 | 13-13 | 2 | 25,613 | Kent Bottenfield | Steve Trachsel | Kent Bottenfield | Steve Trachsel | Troy Percival | 141 | 142 | -1 |
| 2000-05-02 | @ BAL | 27 | L 6-7 | 13-14 | 2 | 34,923 | Scott Schoeneweis | Sidney Ponson | Mike Trombley | Troy Percival | | 147 | 149 | -2 |
| 2000-05-03 | @ BAL | 28 | W 6-5 | 14-14 | 2 | 37,961 | Ramon Ortiz | Jason Johnson | Ramon Ortiz | Jason Johnson | Troy Percival | 153 | 154 | -1 |
| 2000-05-04 | @ BAL | 29 | W 8-5 | 15-14 | 2 | 43,892 | Ken Hill | Mike Mussina | Ken Hill | Mike Mussina | Shigetoshi Hasegawa | 161 | 159 | 2 |
| 2000-05-05 | @ SEA | 30 | W 6-5 | 16-14 | 2 | 38,307 | Kent Bottenfield | Aaron Sele | Kent Bottenfield | Aaron Sele | Troy Percival | 167 | 164 | 3 |
| 2000-05-06 | @ SEA | 31 | L 0-1 | 16-15 | 2 | 43,427 | Kent Mercker | Gil Meche | Kazuhiro Sasaki | Mike Holtz | | 167 | 165 | 2 |
| 2000-05-07 | @ SEA | 32 | L 2-8 | 16-16 | 2 | 42,940 | Scott Schoeneweis | John Halama | John Halama | Scott Schoeneweis | | 169 | 173 | -4 |
| 2000-05-08 | vs OAK | 33 | W 9-8 | 17-16 | 2 | 15,034 | Ramon Ortiz | Ariel Prieto | Mark Petkovsek | T.J. Mathews | Troy Percival | 178 | 181 | -3 |
| 2000-05-09 | vs OAK | 34 | L 2-5 | 17-17 | 2 | 15,308 | Ken Hill | Gil Heredia | Gil Heredia | Ken Hill | Jason Isringhausen | 180 | 186 | -6 |
| 2000-05-10 | vs OAK | 35 | L 4-7 | 17-18 | 3 | 15,300 | Kent Bottenfield | Mark Mulder | Jason Isringhausen | Mark Petkovsek | | 184 | 193 | -9 |
| 2000-05-11 | vs TEX | 36 | W 3-2 | 18-18 | 3 | 15,644 | Kent Mercker | Kenny Rogers | Shigetoshi Hasegawa | Kenny Rogers | Troy Percival | 187 | 195 | -8 |
| 2000-05-12 | vs TEX | 37 | L 11-13 | 18-19 | 3 | 35,305 | Scott Schoeneweis | Doug Davis | Doug Davis | Scott Schoeneweis | John Wetteland | 198 | 208 | -10 |
| 2000-05-13 | vs TEX | 38 | L 5-6 | 18-20 | 3 | 33,236 | Jarrod Washburn | Rick Helling | Rick Helling | Jarrod Washburn | John Wetteland | 203 | 214 | -11 |
| 2000-05-14 | vs TEX | 39 | W 7-6 | 19-20 | 3 | 27,012 | Jason Dickson | Esteban Loaiza | Shigetoshi Hasegawa | Francisco Cordero | | 210 | 220 | -10 |
| 2000-05-16 | vs BAL | 40 | L 3-4 | 19-21 | 4 | 15,881 | Kent Bottenfield | Scott Erickson | Scott Erickson | Kent Bottenfield | Mike Timlin | 213 | 224 | -11 |
| 2000-05-17 | vs BAL | 41 | W 8-7 | 20-21 | 4 | 17,697 | Scott Schoeneweis | Pat Rapp | Troy Percival | Mike Timlin | | 221 | 231 | -10 |
| 2000-05-19 | vs KCA | 42 | W 6-4 | 21-21 | 3 | 26,561 | Jarrod Washburn | Jeff Suppan | Jarrod Washburn | Jeff Suppan | Troy Percival | 227 | 235 | -8 |
| 2000-05-20 | vs KCA | 43 | W 9-8 | 22-21 | 3 | 30,869 | Al Levine | Mac Suzuki | Shigetoshi Hasegawa | Dan Reichert | Troy Percival | 236 | 243 | -7 |
| 2000-05-21 | vs KCA | 44 | L 6-10 | 22-22 | 3 | 28,052 | Kent Bottenfield | Chris Fussell | Jose Santiago | Kent Bottenfield | | 242 | 253 | -11 |
| 2000-05-23 | @ MIN | 45 | W 7-4 | 23-22 | 3 | 9,032 | Brian Cooper | Joe Mays | Brian Cooper | Joe Mays | Troy Percival | 249 | 257 | -8 |
| 2000-05-24 | @ MIN | 46 | W 6-5 | 24-22 | 3 | 8,633 | Jarrod Washburn | Mark Redman | Troy Percival | Bob Wells | Al Levine | 255 | 262 | -7 |
| 2000-05-25 | @ MIN | 47 | W 3-1 | 25-22 | 2 | 13,552 | Scott Schoeneweis | Brad Radke | Scott Schoeneweis | Brad Radke | Troy Percival | 258 | 263 | -5 |
| 2000-05-26 | @ KCA | 48 | L 4-9 | 25-23 | 3 | 22,394 | Seth Etherton | Chris Fussell | Chris Fussell | Eric Weaver | Ricky Bottalico | 262 | 272 | -10 |
| 2000-05-27 | @ KCA | 49 | L 5-6 | 25-24 | 3 | 30,024 | Kent Bottenfield | Jay Witasick | Dan Reichert | Eric Weaver | | 267 | 278 | -11 |
| 2000-05-28 | @ KCA | 50 | W 8-4 | 26-24 | 2 | 23,645 | Brian Cooper | Miguel Batista | Brian Cooper | Miguel Batista | Shigetoshi Hasegawa | 275 | 282 | -7 |
| 2000-05-29 | @ CLE | 51 | W 3-2 | 27-24 | 2 | 42,888 | Jarrod Washburn | Jim Brower | Shigetoshi Hasegawa | Steve Karsay | Troy Percival | 278 | 284 | -6 |
| 2000-05-30 | @ CLE | 52 | L 1-6 | 27-25 | 2 | 42,910 | Scott Schoeneweis | Dave Burba | Dave Burba | Scott Schoeneweis | | 279 | 290 | -11 |
| 2000-05-31 | @ CLE | 53 | L 3-7 | 27-26 | 3 | 41,637 | Seth Etherton | Chuck Finley | Chuck Finley | Seth Etherton | Steve Karsay | 282 | 297 | -15 |
| 2000-06-02 | vs LAN | 54 | W 12-5 | 28-26 | 2 | 43,619 | Kent Bottenfield | Darren Dreifort | Kent Bottenfield | Darren Dreifort | | 294 | 302 | -8 |
| 2000-06-03 | vs LAN | 55 | L 3-8 | 28-27 | 4 | 34,580 | Brian Cooper | Chan Ho Park | Chan Ho Park | Brian Cooper | | 297 | 310 | -13 |
| 2000-06-04 | vs LAN | 56 | W 8-7 | 29-27 | 3 | 40,489 | Jarrod Washburn | Carlos Perez | Troy Percival | Antonio Osuna | | 305 | 317 | -12 |
| 2000-06-05 | vs SFN | 57 | L 4-5 | 29-28 | 4 | 17,924 | Scott Schoeneweis | Livan Hernandez | Aaron Fultz | Shigetoshi Hasegawa | | 309 | 322 | -13 |
| 2000-06-06 | vs SFN | 58 | W 6-5 | 30-28 | 4 | 19,674 | Seth Etherton | Joe Nathan | Troy Percival | Robb Nen | | 315 | 327 | -12 |
| 2000-06-07 | vs SFN | 59 | W 10-9 | 31-28 | 3 | 22,920 | Kent Bottenfield | Russ Ortiz | Shigetoshi Hasegawa | Alan Embree | | 325 | 336 | -11 |
| 2000-06-09 | @ ARI | 60 | L 1-4 | 31-29 | 3 | 39,468 | Brian Cooper | Randy Johnson | Randy Johnson | Brian Cooper | Byung-Hyun Kim | 326 | 340 | -14 |
| 2000-06-10 | @ ARI | 61 | W 10-3 | 32-29 | 3 | 35,213 | Jarrod Washburn | Omar Daal | Jarrod Washburn | Omar Daal | | 336 | 343 | -7 |
| 2000-06-11 | @ ARI | 62 | L 2-3 | 32-30 | 3 | 36,349 | Scott Schoeneweis | Armando Reynoso | Dan Plesac | Scott Schoeneweis | Byung-Hyun Kim | 338 | 346 | -8 |
| 2000-06-13 | @ TBA | 63 | W 5-3 | 33-30 | 3 | 13,483 | Seth Etherton | Bryan Rekar | Seth Etherton | Bryan Rekar | Troy Percival | 343 | 349 | -6 |
| 2000-06-14 | @ TBA | 64 | L 2-3 | 33-31 | 3 | 13,362 | Brian Cooper | Albie Lopez | Albie Lopez | Troy Percival | | 345 | 352 | -7 |
| 2000-06-15 | @ TBA | 65 | L 1-2 | 33-32 | 3 | 13,210 | Jarrod Washburn | Steve Trachsel | Steve Trachsel | Shigetoshi Hasegawa | | 346 | 354 | -8 |
| 2000-06-16 | @ BAL | 66 | L 3-4 | 33-33 | 3 | 45,006 | Scott Schoeneweis | Mike Mussina | Mike Mussina | Scott Schoeneweis | Mike Timlin | 349 | 358 | -9 |
| 2000-06-17 | @ BAL | 67 | W 8-3 | 34-33 | 3 | 45,758 | Tim Belcher | Jason Johnson | Tim Belcher | Jason Johnson | | 357 | 361 | -4 |
| 2000-06-18 | @ BAL | 68 | W 8-6 | 35-33 | 3 | 41,198 | Seth Etherton | Scott Erickson | Seth Etherton | Scott Erickson | Troy Percival | 365 | 367 | -2 |
| 2000-06-20 | vs KCA | 69 | L 6-8 | 35-34 | 3 | 16,711 | Brian Cooper | Jeff Suppan | Jose Santiago | Troy Percival | Ricky Bottalico | 371 | 375 | -4 |
| 2000-06-21 | vs KCA | 70 | W 3-1 | 36-34 | 3 | 16,169 | Jarrod Washburn | Mac Suzuki | Jarrod Washburn | Mac Suzuki | Troy Percival | 374 | 376 | -2 |
| 2000-06-22 | vs KCA | 71 | W 4-3 | 37-34 | 3 | 17,805 | Tim Belcher | Jay Witasick | Tim Belcher | Jay Witasick | Mark Petkovsek | 378 | 379 | -1 |
| 2000-06-23 | vs MIN | 72 | W 8-3 | 38-34 | 3 | 30,254 | Seth Etherton | Jason Ryan | Seth Etherton | Jason Ryan | Al Levine | 386 | 382 | 4 |
| 2000-06-24 | vs MIN | 73 | L 5-11 | 38-35 | 3 | 28,917 | Kent Bottenfield | Eric Milton | Eric Milton | Kent Bottenfield | | 391 | 393 | -2 |
| 2000-06-25 | vs MIN | 74 | W 7-6 | 39-35 | 3 | 19,391 | Brian Cooper | Mark Redman | Shigetoshi Hasegawa | Eddie Guardado | | 398 | 399 | -1 |
| 2000-06-26 | vs MIN | 75 | L 6-10 | 39-36 | 3 | 18,768 | Jarrod Washburn | Brad Radke | Brad Radke | Jarrod Washburn | | 404 | 409 | -5 |
| 2000-06-27 | @ SEA | 76 | L 3-5 | 39-37 | 3 | 32,051 | Tim Belcher | Aaron Sele | Aaron Sele | Tim Belcher | Kazuhiro Sasaki | 407 | 414 | -7 |
| 2000-06-28 | @ SEA | 77 | W 3-2 | 40-37 | 3 | 32,581 | Ken Hill | Jamie Moyer | Ken Hill | Jamie Moyer | Troy Percival | 410 | 416 | -6 |
| 2000-06-29 | @ SEA | 78 | L 2-7 | 40-38 | 3 | 44,387 | Kent Bottenfield | Gil Meche | Jose Paniagua | Kent Bottenfield | | 412 | 423 | -11 |
| 2000-06-30 | vs OAK | 79 | W 7-0 | 41-38 | 3 | 28,765 | Brian Cooper | Mark Mulder | Brian Cooper | Mark Mulder | | 419 | 423 | -4 |
| 2000-07-01 | vs OAK | 80 | W 7-2 | 42-38 | 3 | 31,696 | Jarrod Washburn | Ariel Prieto | Jarrod Washburn | Ariel Prieto | | 426 | 425 | 1 |
| 2000-07-02 | vs OAK | 81 | L 3-10 | 42-39 | 3 | 21,150 | Tim Belcher | Tim Hudson | Tim Hudson | Tim Belcher | | 429 | 435 | -6 |
| 2000-07-03 | vs SEA | 82 | L 6-8 | 42-40 | 3 | 20,919 | Ken Hill | Jamie Moyer | Jamie Moyer | Ken Hill | Kazuhiro Sasaki | 435 | 443 | -8 |
| 2000-07-04 | vs SEA | 83 | W 7-6 | 43-40 | 3 | 43,487 | Kent Bottenfield | Gil Meche | Mark Petkovsek | Jose Mesa | Troy Percival | 442 | 449 | -7 |
| 2000-07-05 | vs SEA | 84 | L 4-6 | 43-41 | 3 | 17,369 | Brian Cooper | John Halama | John Halama | Brian Cooper | Kazuhiro Sasaki | 446 | 455 | -9 |
| 2000-07-06 | vs SEA | 85 | W 5-1 | 44-41 | 3 | 18,790 | Jarrod Washburn | Paul Abbott | Jarrod Washburn | Paul Abbott | | 451 | 456 | -5 |
| 2000-07-07 | vs COL | 86 | W 12-4 | 45-41 | 3 | 29,826 | Ramon Ortiz | Kevin Jarvis | Ramon Ortiz | Kevin Jarvis | | 463 | 460 | 3 |
| 2000-07-08 | vs COL | 87 | W 6-2 | 46-41 | 3 | 22,958 | Ken Hill | Brian Bohanon | Ken Hill | Brian Bohanon | | 469 | 462 | 7 |
| 2000-07-09 | vs COL | 88 | W 10-4 | 47-41 | 3 | 23,820 | Kent Bottenfield | Masato Yoshii | Kent Bottenfield | Masato Yoshii | | 479 | 466 | 13 |
| 2000-07-13 | @ LAN | 89 | L 3-4 | 47-42 | 3 | 35,456 | Ken Hill | Carlos Perez | Antonio Osuna | Al Levine | | 482 | 470 | 12 |
| 2000-07-14 | @ LAN | 90 | W 5-3 | 48-42 | 3 | 53,115 | Kent Bottenfield | Kevin Brown | Kent Bottenfield | Kevin Brown | Troy Percival | 487 | 473 | 14 |
| 2000-07-15 | @ LAN | 91 | W 6-2 | 49-42 | 3 | 42,726 | Seth Etherton | Chan Ho Park | Seth Etherton | Chan Ho Park | | 493 | 475 | 18 |
| 2000-07-16 | @ SDN | 92 | L 5-6 | 49-43 | 3 | 28,941 | Jarrod Washburn | Adam Eaton | Donne Wall | Al Levine | | 498 | 481 | 17 |
| 2000-07-17 | @ SDN | 93 | W 3-2 | 50-43 | 3 | 19,930 | Brian Cooper | Matt Clement | Brian Cooper | Matt Clement | Troy Percival | 501 | 483 | 18 |
| 2000-07-18 | @ SDN | 94 | W 3-2 | 51-43 | 3 | 21,835 | Ken Hill | Brian Tollberg | Al Levine | Trevor Hoffman | | 504 | 485 | 19 |
| 2000-07-19 | vs TEX | 95 | L 2-3 | 51-44 | 3 | 20,083 | Kent Bottenfield | Kenny Rogers | Kenny Rogers | Kent Bottenfield | John Wetteland | 506 | 488 | 18 |
| 2000-07-20 | vs TEX | 96 | W 6-1 | 52-44 | 3 | 23,150 | Seth Etherton | Darren Oliver | Seth Etherton | Darren Oliver | Shigetoshi Hasegawa | 512 | 489 | 23 |
| 2000-07-21 | @ OAK | 97 | W 12-3 | 53-44 | 2 | 13,236 | Jarrod Washburn | Tim Hudson | Jarrod Washburn | Tim Hudson | | 524 | 492 | 32 |
| 2000-07-22 | @ OAK | 98 | L 3-10 | 53-45 | 3 | 20,111 | Brian Cooper | Barry Zito | Barry Zito | Brian Cooper | | 527 | 502 | 25 |
| 2000-07-23 | @ OAK | 99 | L 0-5 | 53-46 | 3 | 19,456 | Ken Hill | Mark Mulder | Mark Mulder | Ken Hill | | 527 | 507 | 20 |
| 2000-07-24 | @ TEX | 100 | W 6-5 | 54-46 | 3 | 33,201 | Kent Bottenfield | Kenny Rogers | Shigetoshi Hasegawa | Tim Crabtree | Troy Percival | 533 | 512 | 21 |
| 2000-07-25 | @ TEX | 101 | L 6-9 | 54-47 | 3 | 34,272 | Seth Etherton | Darren Oliver | Doug Davis | Mike Holtz | John Wetteland | 539 | 521 | 18 |
| 2000-07-26 | @ TEX | 102 | L 5-6 | 54-48 | 3 | 27,858 | Scott Schoeneweis | Matt Perisho | John Wetteland | Al Levine | | 544 | 527 | 17 |
| 2000-07-27 | vs CHA | 103 | L 5-6 | 54-49 | 3 | 24,394 | Brian Cooper | Jon Garland | Jon Garland | Brian Cooper | Keith Foulke | 549 | 533 | 16 |
| 2000-07-28 | vs CHA | 104 | W 10-7 | 55-49 | 3 | 40,711 | Ken Hill | Mike Sirotka | Mike Holtz | Kevin Beirne | Troy Percival | 559 | 540 | 19 |
| 2000-07-29 | vs CHA | 105 | W 6-5 | 56-49 | 3 | 25,881 | Kent Bottenfield | Mark Buehrle | Kent Bottenfield | Lorenzo Barcelo | Troy Percival | 565 | 545 | 20 |
| 2000-07-30 | vs CHA | 106 | L 7-11 | 56-50 | 3 | 27,538 | Seth Etherton | Jim Parque | Keith Foulke | Al Levine | | 572 | 556 | 16 |
| 2000-07-31 | vs DET | 107 | W 5-4 | 57-50 | 3 | 16,797 | Scott Schoeneweis | Jeff Weaver | Mark Petkovsek | Todd Jones | | 577 | 560 | 17 |
| 2000-08-01 | vs DET | 108 | L 3-6 | 57-51 | 3 | 19,104 | Brian Cooper | Adam Bernero | Nelson Cruz | Brian Cooper | Todd Jones | 580 | 566 | 14 |
| 2000-08-02 | vs DET | 109 | L 3-5 | 57-52 | 3 | 29,017 | Ken Hill | Brian Moehler | Brian Moehler | Ken Hill | Todd Jones | 583 | 571 | 12 |
| 2000-08-04 | @ CLE | 110 | L 10-11 | 57-53 | 3 | 43,182 | Seth Etherton | Steve Woodard | Bob Wickman | Troy Percival | | 593 | 582 | 11 |
| 2000-08-05 | @ CLE | 111 | L 3-6 | 57-54 | 3 | 43,162 | Scott Schoeneweis | Chuck Finley | Justin Speier | Scott Schoeneweis | | 596 | 588 | 8 |
| 2000-08-06 | @ CLE | 112 | L 2-5 | 57-55 | 3 | 43,133 | Brian Cooper | Bartolo Colon | Bartolo Colon | Brian Cooper | Bob Wickman | 598 | 593 | 5 |
| 2000-08-07 | vs BOS | 113 | W 4-1 | 58-55 | 3 | 23,078 | Jarrod Washburn | Tomo Ohka | Jarrod Washburn | Tomo Ohka | Shigetoshi Hasegawa | 602 | 594 | 8 |
| 2000-08-08 | vs BOS | 114 | W 2-1 | 59-55 | 3 | 27,293 | Ramon Ortiz | Pedro Martinez | Ramon Ortiz | Pedro Martinez | | 604 | 595 | 9 |
| 2000-08-09 | vs BOS | 115 | L 2-4 | 59-56 | 3 | 25,334 | Matt Wise | Jeff Fassero | Jeff Fassero | Matt Wise | Derek Lowe | 606 | 599 | 7 |
| 2000-08-11 | vs NYA | 116 | W 8-3 | 60-56 | 3 | 43,169 | Scott Schoeneweis | Orlando Hernandez | Scott Schoeneweis | Orlando Hernandez | | 614 | 602 | 12 |
| 2000-08-12 | vs NYA | 117 | W 9-6 | 61-56 | 3 | 43,394 | Kent Mercker | Denny Neagle | Lou Pote | Denny Neagle | Shigetoshi Hasegawa | 623 | 608 | 15 |
| 2000-08-13 | vs NYA | 118 | L 1-4 | 61-57 | 3 | 43,411 | Ramon Ortiz | Roger Clemens | Roger Clemens | Ramon Ortiz | Mariano Rivera | 624 | 612 | 12 |
| 2000-08-15 | @ TOR | 119 | W 8-4 | 62-57 | 3 | 26,706 | Matt Wise | David Wells | Matt Wise | David Wells | | 632 | 616 | 16 |
| 2000-08-16 | @ TOR | 120 | L 6-8 | 62-58 | 3 | 32,497 | Scott Schoeneweis | Steve Trachsel | Billy Koch | Lou Pote | | 638 | 624 | 14 |
| 2000-08-17 | @ NYA | 121 | L 1-6 | 62-59 | 3 | 35,180 | Kent Mercker | Denny Neagle | Denny Neagle | Kent Mercker | | 639 | 630 | 9 |
| 2000-08-18 | @ NYA | 122 | W 9-8 | 63-59 | 3 | 37,503 | Ramon Ortiz | Roger Clemens | Shigetoshi Hasegawa | Mike Stanton | | 648 | 638 | 10 |
| 2000-08-19 | @ NYA | 123 | L 1-9 | 63-60 | 3 | 49,491 | Brian Cooper | Andy Pettitte | Andy Pettitte | Brian Cooper | | 649 | 647 | 2 |
| 2000-08-20 | @ NYA | 124 | W 5-4 | 64-60 | 3 | 50,048 | Matt Wise | David Cone | Matt Wise | Jeff Nelson | Shigetoshi Hasegawa | 654 | 651 | 3 |
| 2000-08-21 | @ BOS | 125 | L 6-7 | 64-61 | 3 | 32,795 | Scott Schoeneweis | Rolando Arrojo | Derek Lowe | Mike Holtz | | 660 | 658 | 2 |
| 2000-08-22 | @ BOS | 126 | W 11-4 | 65-61 | 3 | 33,163 | Kent Mercker | Tim Wakefield | Kent Mercker | Tim Wakefield | | 671 | 662 | 9 |
| 2000-08-23 | @ BOS | 127 | L 1-3 | 65-62 | 3 | 32,958 | Ramon Ortiz | Tomo Ohka | Tomo Ohka | Ramon Ortiz | Derek Lowe | 672 | 665 | 7 |
| 2000-08-25 | vs CLE | 128 | W 4-1 | 66-62 | 3 | 41,452 | Matt Wise | Dave Burba | Matt Wise | Dave Burba | Shigetoshi Hasegawa | 676 | 666 | 10 |
| 2000-08-26 | vs CLE | 129 | L 5-9 | 66-63 | 3 | 37,697 | Scott Schoeneweis | Jason Bere | Jason Bere | Scott Schoeneweis | | 681 | 675 | 6 |
| 2000-08-27 | vs CLE | 130 | W 10-9 | 67-63 | 3 | 31,504 | Kent Mercker | Chuck Finley | Al Levine | Chuck Finley | Shigetoshi Hasegawa | 691 | 684 | 7 |
| 2000-08-28 | vs TOR | 131 | L 2-4 | 67-64 | 3 | 17,483 | Ramon Ortiz | Esteban Loaiza | Esteban Loaiza | Ramon Ortiz | Billy Koch | 693 | 688 | 5 |
| 2000-08-29 | vs TOR | 132 | W 9-4 | 68-64 | 3 | 17,773 | Scott Karl | Chris Carpenter | Mike Holtz | Chris Carpenter | | 702 | 692 | 10 |
| 2000-08-30 | vs TOR | 133 | L 2-11 | 68-65 | 3 | 19,653 | Matt Wise | David Wells | David Wells | Matt Wise | | 704 | 703 | 1 |
| 2000-09-01 | @ CHA | 134 | L 8-9 | 68-66 | 3 | 16,377 | Scott Schoeneweis | Sean Lowe | Matt Ginter | Shigetoshi Hasegawa | Keith Foulke | 712 | 712 | 0 |
| 2000-09-02 | @ CHA | 135 | L 6-13 | 68-67 | 3 | 29,785 | Kent Mercker | Jim Parque | Jim Parque | Kent Mercker | | 718 | 725 | -7 |
| 2000-09-03 | @ CHA | 136 | L 12-13 | 68-68 | 3 | 22,020 | Ramon Ortiz | James Baldwin | Kelly Wunsch | Shigetoshi Hasegawa | Keith Foulke | 730 | 738 | -8 |
| 2000-09-04 | @ DET | 137 | L 0-5 | 68-69 | 3 | 26,364 | Scott Karl | Hideo Nomo | Hideo Nomo | Scott Karl | | 730 | 743 | -13 |
| 2000-09-05 | @ DET | 138 | L 5-7 | 68-70 | 3 | 20,322 | Matt Wise | Brian Moehler | Brian Moehler | Matt Wise | Todd Jones | 735 | 750 | -15 |
| 2000-09-06 | @ DET | 139 | W 1-0 | 69-70 | 3 | 20,937 | Scott Schoeneweis | Steve Sparks | Scott Schoeneweis | Steve Sparks | Troy Percival | 736 | 750 | -14 |
| 2000-09-07 | @ DET | 140 | W 6-4 | 70-70 | 3 | 27,513 | Tim Belcher | Dave Mlicki | Tim Belcher | Dave Mlicki | Shigetoshi Hasegawa | 742 | 754 | -12 |
| 2000-09-08 | vs BAL | 141 | W 2-1 | 71-70 | 3 | 30,480 | Ramon Ortiz | Pat Rapp | Ramon Ortiz | Pat Rapp | Troy Percival | 744 | 755 | -11 |
| 2000-09-09 | vs BAL | 142 | L 3-10 | 71-71 | 3 | 22,332 | Scott Karl | Jose Mercedes | Jose Mercedes | Scott Karl | | 747 | 765 | -18 |
| 2000-09-10 | vs BAL | 143 | W 2-1 | 72-71 | 3 | 22,606 | Al Levine | Mike Mussina | Shigetoshi Hasegawa | Mike Mussina | Troy Percival | 749 | 766 | -17 |
| 2000-09-11 | vs BAL | 144 | L 1-3 | 72-72 | 3 | 17,323 | Scott Schoeneweis | Sidney Ponson | Sidney Ponson | Scott Schoeneweis | | 750 | 769 | -19 |
| 2000-09-12 | vs TBA | 145 | W 5-2 | 73-72 | 3 | 15,689 | Tim Belcher | Bryan Rekar | Tim Belcher | Bryan Rekar | Troy Percival | 755 | 771 | -16 |
| 2000-09-13 | vs TBA | 146 | W 8-4 | 74-72 | 3 | 16,686 | Ramon Ortiz | Cory Lidle | Ramon Ortiz | Cory Lidle | | 763 | 775 | -12 |
| 2000-09-15 | @ MIN | 147 | W 16-5 | 75-72 | 3 | 10,129 | Al Levine | Matt Kinney | Scott Karl | Matt Kinney | | 779 | 780 | -1 |
| 2000-09-16 | @ MIN | 148 | W 7-6 | 76-72 | 3 | 10,078 | Scott Schoeneweis | Johan Santana | Shigetoshi Hasegawa | LaTroy Hawkins | Troy Percival | 786 | 786 | 0 |
| 2000-09-17 | @ MIN | 149 | L 0-1 | 76-73 | 3 | 7,231 | Tim Belcher | Brad Radke | Brad Radke | Tim Belcher | | 786 | 787 | -1 |
| 2000-09-19 | @ KCA | 150 | L 1-5 | 76-74 | 3 | 12,873 | Ramon Ortiz | Blake Stein | Blake Stein | Ramon Ortiz | | 787 | 792 | -5 |
| 2000-09-20 | @ KCA | 151 | W 7-4 | 77-74 | 3 | 11,442 | Al Levine | Mac Suzuki | Troy Percival | Jose Santiago | Mark Petkovsek | 794 | 796 | -2 |
| 2000-09-21 | @ KCA | 152 | L 3-8 | 77-75 | 3 | 12,690 | Scott Schoeneweis | Jeff Suppan | Jeff Suppan | Scott Schoeneweis | | 797 | 804 | -7 |
| 2000-09-22 | @ TEX | 153 | W 2-1 | 78-75 | 3 | 38,739 | Lou Pote | Darren Oliver | Ben Weber | Darren Oliver | Troy Percival | 799 | 805 | -6 |
| 2000-09-23 | @ TEX | 154 | W 15-4 | 79-75 | 3 | 45,543 | Derrick Turnbow | Rick Helling | Scott Karl | Rick Helling | | 814 | 809 | 5 |
| 2000-09-24 | @ TEX | 155 | W 9-2 | 80-75 | 3 | 32,061 | Ramon Ortiz | Kenny Rogers | Ramon Ortiz | Jonathan Johnson | | 823 | 811 | 12 |
| 2000-09-25 | @ OAK | 156 | L 5-7 | 80-76 | 3 | 14,248 | Tim Belcher | Barry Zito | Barry Zito | Tim Belcher | | 828 | 818 | 10 |
| 2000-09-26 | @ OAK | 157 | L 3-10 | 80-77 | 3 | 22,234 | Scott Schoeneweis | Tim Hudson | Tim Hudson | Scott Schoeneweis | | 831 | 828 | 3 |
| 2000-09-27 | @ OAK | 158 | L 7-9 | 80-78 | 3 | 23,333 | Al Levine | Gil Heredia | Doug Jones | Mike Holtz | Jason Isringhausen | 838 | 837 | 1 |
| 2000-09-28 | @ OAK | 159 | W 6-3 | 81-78 | 3 | 12,523 | Scott Karl | Kevin Appier | Mike Holtz | Scott Service | Troy Percival | 844 | 840 | 4 |
| 2000-09-29 | vs SEA | 160 | W 9-3 | 82-78 | 3 | 33,424 | Ramon Ortiz | Paul Abbott | Ramon Ortiz | Paul Abbott | Lou Pote | 853 | 843 | 10 |
| 2000-09-30 | vs SEA | 161 | L 9-21 | 82-79 | 3 | 35,238 | Tim Belcher | John Halama | John Halama | Tim Belcher | | 862 | 864 | -2 |
| 2000-10-01 | vs SEA | 162 | L 2-5 | 82-80 | 3 | 30,473 | Mark Petkovsek | Aaron Sele | Arthur Rhodes | Shigetoshi Hasegawa | Kazuhiro Sasaki | 864 | 869 | -5 |