| 2000-04-03 | @ ANA | 1 | W 3-2 | 1-0 | 1 | 42,704 | Orlando Hernandez | Ken Hill | Orlando Hernandez | Ken Hill | Mariano Rivera | 3 | 2 | 1 |
| 2000-04-04 | @ ANA | 2 | W 5-3 | 2-0 | 2 | 25,818 | Roger Clemens | Kent Bottenfield | Ramiro Mendoza | Troy Percival | Mariano Rivera | 8 | 5 | 3 |
| 2000-04-05 | @ ANA | 3 | L 6-12 | 2-1 | 1 | 24,560 | David Cone | Scott Schoeneweis | Scott Schoeneweis | David Cone | | 14 | 17 | -3 |
| 2000-04-07 | @ SEA | 4 | L 5-7 | 2-2 | 2 | 40,827 | Andy Pettitte | John Halama | John Halama | Andy Pettitte | Kazuhiro Sasaki | 19 | 24 | -5 |
| 2000-04-08 | @ SEA | 5 | W 3-2 | 3-2 | 2 | 45,261 | Orlando Hernandez | Gil Meche | Jeff Nelson | Jose Mesa | Mariano Rivera | 22 | 26 | -4 |
| 2000-04-09 | @ SEA | 6 | L 3-9 | 3-3 | 2 | 45,488 | Roger Clemens | Jamie Moyer | Jamie Moyer | Roger Clemens | | 25 | 35 | -10 |
| 2000-04-12 | vs TEX | 7 | W 8-6 | 4-3 | 2 | 48,487 | David Cone | Darren Oliver | Jeff Nelson | Mike Munoz | Mariano Rivera | 33 | 41 | -8 |
| 2000-04-13 | vs TEX | 8 | W 5-1 | 5-3 | 1 | 23,805 | Orlando Hernandez | Kenny Rogers | Orlando Hernandez | Kenny Rogers | | 38 | 42 | -4 |
| 2000-04-14 | vs KCA | 9 | W 7-5 | 6-3 | 1 | 33,094 | Roger Clemens | Jay Witasick | Roger Clemens | Jay Witasick | Mariano Rivera | 45 | 47 | -2 |
| 2000-04-15 | vs KCA | 10 | W 7-1 | 7-3 | 1 | 34,056 | Ramiro Mendoza | Jose Rosado | Ramiro Mendoza | Jose Rosado | | 52 | 48 | 4 |
| 2000-04-16 | vs KCA | 11 | W 8-4 | 8-3 | 1 | 36,724 | Jason Grimsley | Chad Durbin | Jeff Nelson | Chris Fussell | | 60 | 52 | 8 |
| 2000-04-17 | @ TEX | 12 | W 5-4 | 9-3 | 1 | 38,166 | David Cone | Darren Oliver | Mariano Rivera | Tim Crabtree | Todd Erdos | 65 | 56 | 9 |
| 2000-04-18 | @ TEX | 13 | W 6-3 | 10-3 | 1 | 43,644 | Orlando Hernandez | Kenny Rogers | Orlando Hernandez | Kenny Rogers | | 71 | 59 | 12 |
| 2000-04-19 | @ TEX | 14 | W 5-4 | 11-3 | 1 | 39,294 | Roger Clemens | Rick Helling | Mariano Rivera | Jeff Zimmerman | | 76 | 63 | 13 |
| 2000-04-21 | @ TOR | 15 | L 3-8 | 11-4 | 1 | 25,921 | Ramiro Mendoza | Chris Carpenter | Chris Carpenter | Ramiro Mendoza | | 79 | 71 | 8 |
| 2000-04-22 | @ TOR | 16 | L 2-8 | 11-5 | 2 | 30,167 | David Cone | Kelvim Escobar | Kelvim Escobar | David Cone | | 81 | 79 | 2 |
| 2000-04-23 | @ TOR | 17 | W 10-7 | 12-5 | 1 | 20,485 | Orlando Hernandez | Frank Castillo | Orlando Hernandez | Clayton Andrews | Mariano Rivera | 91 | 86 | 5 |
| 2000-04-24 | vs MIN | 18 | L 3-7 | 12-6 | 1 | 35,693 | Roger Clemens | Eric Milton | Eric Milton | Roger Clemens | | 94 | 93 | 1 |
| 2000-04-25 | vs MIN | 19 | L 1-6 | 12-7 | 2 | 27,372 | Ramiro Mendoza | Sean Bergman | Sean Bergman | Ramiro Mendoza | | 95 | 99 | -4 |
| 2000-04-26 | vs MIN | 20 | W 2-0 | 13-7 | 1 | 27,919 | Andy Pettitte | Joe Mays | Jeff Nelson | Joe Mays | Mariano Rivera | 97 | 99 | -2 |
| 2000-04-28 | vs TOR | 21 | W 6-0 | 14-7 | 1 | 35,987 | David Cone | Kelvim Escobar | David Cone | Kelvim Escobar | | 103 | 99 | 4 |
| 2000-04-29 | vs TOR | 22 | L 2-6 | 14-8 | 1 | 38,783 | Orlando Hernandez | David Wells | David Wells | Orlando Hernandez | Billy Koch | 105 | 105 | 0 |
| 2000-04-30 | vs TOR | 23 | W 7-1 | 15-8 | 1 | 43,721 | Roger Clemens | Roy Halladay | Roger Clemens | Roy Halladay | | 112 | 106 | 6 |
| 2000-05-01 | @ CLE | 24 | W 2-1 | 16-8 | 1 | 42,711 | Ramiro Mendoza | Jaret Wright | Ramiro Mendoza | Jaret Wright | Mariano Rivera | 114 | 107 | 7 |
| 2000-05-02 | @ CLE | 25 | W 4-2 | 17-8 | 1 | 42,801 | Andy Pettitte | Bobby Witt | Andy Pettitte | Bobby Witt | Mariano Rivera | 118 | 109 | 9 |
| 2000-05-03 | @ CLE | 26 | W 6-5 | 18-8 | 1 | 42,837 | David Cone | Dave Burba | Jason Grimsley | Steve Karsay | Mariano Rivera | 124 | 114 | 10 |
| 2000-05-05 | vs BAL | 27 | W 12-10 | 19-8 | 1 | 42,244 | Orlando Hernandez | Scott Erickson | Jeff Nelson | B.J. Ryan | | 136 | 124 | 12 |
| 2000-05-06 | vs BAL | 28 | W 3-1 | 20-8 | 1 | 54,350 | Roger Clemens | Pat Rapp | Roger Clemens | Pat Rapp | Mariano Rivera | 139 | 125 | 14 |
| 2000-05-07 | vs BAL | 29 | L 6-7 | 20-9 | 1 | 52,559 | Ramiro Mendoza | Sidney Ponson | Buddy Groom | Mariano Rivera | Mike Timlin | 145 | 132 | 13 |
| 2000-05-08 | vs TBA | 30 | W 6-3 | 21-9 | 1 | 25,361 | Andy Pettitte | Dwight Gooden | Andy Pettitte | Dwight Gooden | Mariano Rivera | 151 | 135 | 16 |
| 2000-05-09 | vs TBA | 31 | W 4-3 | 22-9 | 1 | 23,097 | David Cone | Esteban Yan | Jeff Nelson | Rick White | | 155 | 138 | 17 |
| 2000-05-11 | vs TBA | 32 | L 0-1 | 22-10 | 1 | 14,292 | Orlando Hernandez | Steve Trachsel | Steve Trachsel | Orlando Hernandez | Albie Lopez | 155 | 139 | 16 |
| 2000-05-12 | @ DET | 33 | L 7-9 | 22-11 | 1 | 33,326 | Roger Clemens | C.J. Nitkowski | C.J. Nitkowski | Roger Clemens | Todd Jones | 162 | 148 | 14 |
| 2000-05-13 | @ DET | 34 | L 3-6 | 22-12 | 1 | 36,520 | Andy Pettitte | Jeff Weaver | Jeff Weaver | Andy Pettitte | Todd Jones | 165 | 154 | 11 |
| 2000-05-14 | @ DET | 35 | L 1-2 | 22-13 | 2 | 31,313 | David Cone | Dave Mlicki | Dave Mlicki | David Cone | Todd Jones | 166 | 156 | 10 |
| 2000-05-16 | vs CHA | 36 | L 0-4 | 22-14 | 2 | 31,143 | Orlando Hernandez | Cal Eldred | Cal Eldred | Orlando Hernandez | | 166 | 160 | 6 |
| 2000-05-17 | vs CHA | 37 | W 9-4 | 23-14 | 2 | 26,887 | Roger Clemens | Jim Parque | Roger Clemens | Jim Parque | | 175 | 164 | 11 |
| 2000-05-19 | @ CLE | 38 | W 11-7 | 24-14 | 2 | 42,642 | Andy Pettitte | Dave Burba | Ramiro Mendoza | Scott Kamieniecki | | 186 | 171 | 15 |
| 2000-05-20 | @ CLE | 39 | L 2-3 | 24-15 | 2 | 42,583 | David Cone | Chuck Finley | Paul Shuey | Jeff Nelson | | 188 | 174 | 14 |
| 2000-05-21 | @ CLE | 40 | L 1-6 | 24-16 | 2 | 42,587 | Orlando Hernandez | Paul Rigdon | Paul Rigdon | Orlando Hernandez | | 189 | 180 | 9 |
| 2000-05-23 | @ CHA | 41 | L 2-8 | 24-17 | 2 | 21,863 | Roger Clemens | Kip Wells | Kip Wells | Roger Clemens | | 191 | 188 | 3 |
| 2000-05-24 | @ CHA | 42 | W 12-4 | 25-17 | 2 | 23,144 | Andy Pettitte | Mike Sirotka | Andy Pettitte | Mike Sirotka | | 203 | 192 | 11 |
| 2000-05-25 | @ CHA | 43 | W 7-0 | 26-17 | 2 | 23,636 | Ramiro Mendoza | James Baldwin | Ramiro Mendoza | James Baldwin | | 210 | 192 | 18 |
| 2000-05-26 | vs BOS | 44 | L 1-4 | 26-18 | 2 | 54,470 | David Cone | Ramon Martinez | Ramon Martinez | David Cone | Derek Lowe | 211 | 196 | 15 |
| 2000-05-27 | vs BOS | 45 | W 8-3 | 27-18 | 2 | 55,671 | Jason Grimsley | Brian Rose | Mike Stanton | John Wasdin | | 219 | 199 | 20 |
| 2000-05-28 | vs BOS | 46 | L 0-2 | 27-19 | 2 | 55,339 | Roger Clemens | Pedro Martinez | Pedro Martinez | Roger Clemens | | 219 | 201 | 18 |
| 2000-05-29 | vs OAK | 47 | W 4-1 | 28-19 | 2 | 41,284 | Andy Pettitte | Omar Olivares | Andy Pettitte | Omar Olivares | | 223 | 202 | 21 |
| 2000-05-30 | vs OAK | 48 | L 4-7 | 28-20 | 2 | 26,360 | Ramiro Mendoza | Kevin Appier | Kevin Appier | Ramiro Mendoza | Jason Isringhausen | 227 | 209 | 18 |
| 2000-05-31 | vs OAK | 49 | L 7-8 | 28-21 | 2 | 30,178 | David Cone | Gil Heredia | Gil Heredia | David Cone | Jason Isringhausen | 234 | 217 | 17 |
| 2000-06-02 | @ ATL | 50 | W 5-2 | 29-21 | 2 | 48,524 | Orlando Hernandez | Kevin Millwood | Orlando Hernandez | Kevin Millwood | Mariano Rivera | 239 | 219 | 20 |
| 2000-06-03 | @ ATL | 51 | L 7-11 | 29-22 | 2 | 48,423 | Roger Clemens | Greg Maddux | Mike Remlinger | Jason Grimsley | | 246 | 230 | 16 |
| 2000-06-04 | @ ATL | 52 | W 7-6 | 30-22 | 1 | 47,756 | Andy Pettitte | Terry Mulholland | Andy Pettitte | Terry Mulholland | Mariano Rivera | 253 | 236 | 17 |
| 2000-06-05 | @ MON | 53 | L 4-6 | 30-23 | 2 | 18,095 | David Cone | Dustin Hermanson | Mike Johnson | David Cone | Steve Kline | 257 | 242 | 15 |
| 2000-06-06 | @ MON | 54 | W 8-1 | 31-23 | 2 | 24,453 | Jason Grimsley | Javier Vazquez | Jason Grimsley | Javier Vazquez | | 265 | 243 | 22 |
| 2000-06-07 | @ MON | 55 | W 7-2 | 32-23 | 1 | 25,381 | Orlando Hernandez | Carl Pavano | Orlando Hernandez | Carl Pavano | | 272 | 245 | 27 |
| 2000-06-09 | vs NYN | 56 | L 2-12 | 32-24 | 1 | 55,822 | Roger Clemens | Al Leiter | Al Leiter | Roger Clemens | | 274 | 257 | 17 |
| 2000-06-10 | vs NYN | 57 | W 13-5 | 33-24 | 1 | 55,839 | Andy Pettitte | Robert Joseph Jones | Andy Pettitte | Robert Joseph Jones | | 287 | 262 | 25 |
| 2000-06-13 | vs BOS | 58 | L 3-5 | 33-25 | 1 | 52,142 | Orlando Hernandez | Brian Rose | Hipolito Pichardo | Orlando Hernandez | Derek Lowe | 290 | 267 | 23 |
| 2000-06-14 | vs BOS | 59 | W 2-1 | 34-25 | 1 | 54,834 | Roger Clemens | Pedro Martinez | Jason Grimsley | Tim Wakefield | Mariano Rivera | 292 | 268 | 24 |
| 2000-06-15 | vs CHA | 60 | L 3-12 | 34-26 | 1 | 30,803 | Andy Pettitte | Mike Sirotka | Mike Sirotka | Andy Pettitte | | 295 | 280 | 15 |
| 2000-06-16 | vs CHA | 61 | L 1-3 | 34-27 | 2 | 41,910 | David Cone | James Baldwin | James Baldwin | Mike Stanton | Bob Howry | 296 | 283 | 13 |
| 2000-06-17 | vs CHA | 62 | L 9-10 | 34-28 | 2 | 54,053 | Jake Westbrook | Cal Eldred | Cal Eldred | Jake Westbrook | Keith Foulke | 305 | 293 | 12 |
| 2000-06-18 | vs CHA | 63 | L 4-17 | 34-29 | 2 | 52,856 | Orlando Hernandez | Jim Parque | Jim Parque | Orlando Hernandez | | 309 | 310 | -1 |
| 2000-06-19 | @ BOS | 64 | W 22-1 | 35-29 | 1 | 33,370 | Ramiro Mendoza | Brian Rose | Ramiro Mendoza | Brian Rose | | 331 | 311 | 20 |
| 2000-06-20 | @ BOS | 65 | W 3-0 | 36-29 | 1 | 33,909 | Andy Pettitte | Pedro Martinez | Andy Pettitte | Pedro Martinez | Mariano Rivera | 334 | 311 | 23 |
| 2000-06-21 | @ BOS | 66 | L 7-9 | 36-30 | 1 | 32,958 | David Cone | Pete Schourek | Rich Garces | Jason Grimsley | | 341 | 320 | 21 |
| 2000-06-22 | @ BOS | 67 | L 2-4 | 36-31 | 2 | 33,744 | Jake Westbrook | Ramon Martinez | Ramon Martinez | Jake Westbrook | Derek Lowe | 343 | 324 | 19 |
| 2000-06-23 | @ CHA | 68 | L 3-4 | 36-32 | 3 | 38,773 | Ben Ford | Jim Parque | Sean Lowe | Mariano Rivera | | 346 | 328 | 18 |
| 2000-06-24 | @ CHA | 69 | W 12-8 | 37-32 | 2 | 32,623 | Ramiro Mendoza | Kip Wells | Ramiro Mendoza | Kip Wells | Mariano Rivera | 358 | 336 | 22 |
| 2000-06-25 | @ CHA | 70 | L 7-8 | 37-33 | 2 | 40,817 | Andy Pettitte | Mike Sirotka | Mike Sirotka | Andy Pettitte | Bob Howry | 365 | 344 | 21 |
| 2000-06-27 | @ DET | 71 | L 6-7 | 37-34 | 2 | 37,512 | David Cone | Hideo Nomo | Nelson Cruz | Mariano Rivera | | 371 | 351 | 20 |
| 2000-06-28 | @ DET | 72 | L 6-13 | 37-35 | 2 | 39,212 | Ben Ford | Willie Blair | Willie Blair | Ben Ford | Steve Sparks | 377 | 364 | 13 |
| 2000-06-29 | @ DET | 73 | W 8-0 | 38-35 | 2 | 39,586 | Andy Pettitte | Dave Mlicki | Andy Pettitte | Dave Mlicki | | 385 | 364 | 21 |
| 2000-06-30 | @ TBA | 74 | L 4-6 | 38-36 | 2 | 30,323 | Jason Grimsley | Bryan Rekar | Jim Mecir | Jeff Nelson | Roberto Hernandez | 389 | 370 | 19 |
| 2000-07-01 | @ TBA | 75 | W 6-1 | 39-36 | 2 | 37,990 | Orlando Hernandez | Albie Lopez | Orlando Hernandez | Albie Lopez | | 395 | 371 | 24 |
| 2000-07-02 | @ TBA | 76 | W 5-2 | 40-36 | 2 | 31,118 | Roger Clemens | Steve Trachsel | Roger Clemens | Steve Trachsel | Mariano Rivera | 400 | 373 | 27 |
| 2000-07-04 | vs BAL | 77 | L 6-7 | 40-37 | 2 | 44,447 | David Cone | Scott Erickson | Scott Erickson | David Cone | Mike Trombley | 406 | 380 | 26 |
| 2000-07-05 | vs BAL | 78 | W 12-6 | 41-37 | 2 | 40,031 | Andy Pettitte | Pat Rapp | Andy Pettitte | Pat Rapp | | 418 | 386 | 32 |
| 2000-07-06 | vs BAL | 79 | W 13-9 | 42-37 | 2 | 44,104 | Ed Yarnall | Sidney Ponson | Mike Stanton | Jason Johnson | | 431 | 395 | 36 |
| 2000-07-07 | @ NYN | 80 | W 2-1 | 43-37 | 1 | 54,132 | Orlando Hernandez | Al Leiter | Orlando Hernandez | Al Leiter | Mariano Rivera | 433 | 396 | 37 |
| 2000-07-08 | @ NYN | 81 | W 4-2 | 44-37 | 1 | 54,165 | Dwight Gooden | Robert Joseph Jones | Dwight Gooden | Robert Joseph Jones | Mariano Rivera | 437 | 398 | 39 |
| 2000-07-08 | vs NYN | 82 | W 4-2 | 44-37 | 1 | 55,821 | Roger Clemens | Glendon Rusch | Roger Clemens | Glendon Rusch | Mariano Rivera | 441 | 400 | 41 |
| 2000-07-09 | @ NYN | 83 | L 0-2 | 45-38 | 1 | 54,286 | Andy Pettitte | Mike Hampton | Mike Hampton | Andy Pettitte | Armando Benitez | 441 | 402 | 39 |
| 2000-07-13 | vs FLO | 84 | L 9-11 | 45-39 | 1 | 33,323 | Orlando Hernandez | Brad Penny | Brad Penny | Orlando Hernandez | Antonio Alfonseca | 450 | 413 | 37 |
| 2000-07-14 | vs FLO | 85 | W 6-2 | 46-39 | 1 | 35,332 | Roger Clemens | Ryan Dempster | Roger Clemens | Ryan Dempster | | 456 | 415 | 41 |
| 2000-07-16 | vs PHI | 86 | W 9-8 | 47-39 | 1 | 53,131 | Andy Pettitte | Paul Byrd | Mariano Rivera | Jeff Brantley | | 465 | 423 | 42 |
| 2000-07-17 | vs PHI | 87 | L 8-10 | 47-40 | 1 | 38,987 | David Cone | Dave Coggin | Dave Coggin | David Cone | Chris Brock | 473 | 433 | 40 |
| 2000-07-18 | vs PHI | 88 | W 3-1 | 48-40 | 1 | 40,013 | Denny Neagle | Curt Schilling | Denny Neagle | Curt Schilling | Mariano Rivera | 476 | 434 | 42 |
| 2000-07-19 | vs DET | 89 | W 9-1 | 49-40 | 1 | 32,420 | Roger Clemens | Hideo Nomo | Roger Clemens | Hideo Nomo | | 485 | 435 | 50 |
| 2000-07-20 | vs DET | 90 | L 3-5 | 49-41 | 1 | 45,535 | Andy Pettitte | Willie Blair | Willie Blair | Andy Pettitte | Todd Jones | 488 | 440 | 48 |
| 2000-07-21 | vs TBA | 91 | W 11-1 | 50-41 | 1 | 39,518 | Dwight Gooden | Esteban Yan | Dwight Gooden | Esteban Yan | | 499 | 441 | 58 |
| 2000-07-22 | vs TBA | 92 | L 4-12 | 50-42 | 1 | 47,375 | David Cone | Ryan Rupe | Ryan Rupe | David Cone | | 503 | 453 | 50 |
| 2000-07-23 | vs TBA | 93 | W 5-1 | 51-42 | 1 | 45,528 | Denny Neagle | Bryan Rekar | Denny Neagle | Bryan Rekar | | 508 | 454 | 54 |
| 2000-07-24 | @ BAL | 94 | W 4-3 | 52-42 | 1 | 47,450 | Roger Clemens | John Parrish | Roger Clemens | John Parrish | Mariano Rivera | 512 | 457 | 55 |
| 2000-07-25 | @ BAL | 95 | W 19-1 | 53-42 | 1 | 47,874 | Andy Pettitte | Scott Erickson | Andy Pettitte | Scott Erickson | | 531 | 458 | 73 |
| 2000-07-26 | @ BAL | 96 | W 4-1 | 54-42 | 1 | 47,691 | Dwight Gooden | Sidney Ponson | Dwight Gooden | Sidney Ponson | Mariano Rivera | 535 | 459 | 76 |
| 2000-07-27 | @ MIN | 97 | L 3-9 | 54-43 | 1 | 16,325 | David Cone | Mark Redman | Mark Redman | David Cone | | 538 | 468 | 70 |
| 2000-07-28 | @ MIN | 98 | W 9-5 | 55-43 | 1 | 16,823 | Denny Neagle | Brad Radke | Mariano Rivera | Eddie Guardado | | 547 | 473 | 74 |
| 2000-07-29 | @ MIN | 99 | L 2-6 | 55-44 | 1 | 31,426 | Roger Clemens | Eric Milton | Eric Milton | Ramiro Mendoza | | 549 | 479 | 70 |
| 2000-07-30 | @ MIN | 100 | W 7-4 | 56-44 | 1 | 19,041 | Andy Pettitte | Joe Mays | Andy Pettitte | Joe Mays | | 556 | 483 | 73 |
| 2000-08-01 | vs KCA | 101 | W 5-4 | 57-44 | 1 | 32,649 | Dwight Gooden | Dan Reichert | Jeff Nelson | Ricky Bottalico | Mariano Rivera | 561 | 487 | 74 |
| 2000-08-02 | vs KCA | 102 | L 1-4 | 57-45 | 1 | 38,993 | Denny Neagle | Blake Stein | Blake Stein | Denny Neagle | Ricky Bottalico | 562 | 491 | 71 |
| 2000-08-03 | vs KCA | 103 | W 3-2 | 58-45 | 1 | 33,829 | Roger Clemens | Mac Suzuki | Mariano Rivera | Jerry Spradlin | | 565 | 493 | 72 |
| 2000-08-04 | vs SEA | 104 | W 13-6 | 59-45 | 1 | 46,592 | Andy Pettitte | Jamie Moyer | Andy Pettitte | Jamie Moyer | | 578 | 499 | 79 |
| 2000-08-05 | vs SEA | 105 | L 5-6 | 59-46 | 1 | 55,629 | David Cone | Aaron Sele | Brett Tomko | Dwight Gooden | Kazuhiro Sasaki | 583 | 505 | 78 |
| 2000-08-06 | vs SEA | 106 | L 1-11 | 59-47 | 1 | 52,720 | Orlando Hernandez | Paul Abbott | Paul Abbott | Orlando Hernandez | | 584 | 516 | 68 |
| 2000-08-07 | vs SEA | 107 | L 5-8 | 59-48 | 1 | 38,421 | Denny Neagle | John Halama | John Halama | Denny Neagle | | 589 | 524 | 65 |
| 2000-08-08 | vs OAK | 108 | W 4-3 | 60-48 | 1 | 36,357 | Roger Clemens | Barry Zito | Mariano Rivera | Jason Isringhausen | | 593 | 527 | 66 |
| 2000-08-09 | vs OAK | 109 | W 12-1 | 61-48 | 1 | 33,466 | Andy Pettitte | Kevin Appier | Andy Pettitte | Kevin Appier | | 605 | 528 | 77 |
| 2000-08-10 | vs OAK | 110 | W 12-6 | 62-48 | 1 | 41,011 | David Cone | Mark Mulder | David Cone | Mark Mulder | | 617 | 534 | 83 |
| 2000-08-11 | @ ANA | 111 | L 3-8 | 62-49 | 1 | 43,169 | Orlando Hernandez | Scott Schoeneweis | Scott Schoeneweis | Orlando Hernandez | | 620 | 542 | 78 |
| 2000-08-12 | @ ANA | 112 | L 6-9 | 62-50 | 1 | 43,394 | Denny Neagle | Kent Mercker | Lou Pote | Denny Neagle | Shigetoshi Hasegawa | 626 | 551 | 75 |
| 2000-08-13 | @ ANA | 113 | W 4-1 | 63-50 | 1 | 43,411 | Roger Clemens | Ramon Ortiz | Roger Clemens | Ramon Ortiz | Mariano Rivera | 630 | 552 | 78 |
| 2000-08-14 | @ TEX | 114 | W 7-3 | 64-50 | 1 | 36,260 | Andy Pettitte | Matt Perisho | Andy Pettitte | Matt Perisho | | 637 | 555 | 82 |
| 2000-08-15 | @ TEX | 115 | W 10-2 | 65-50 | 1 | 35,365 | David Cone | Doug Davis | David Cone | Doug Davis | Dwight Gooden | 647 | 557 | 90 |
| 2000-08-16 | @ TEX | 116 | L 0-5 | 65-51 | 1 | 34,446 | Orlando Hernandez | Brian Sikorski | Brian Sikorski | Orlando Hernandez | | 647 | 562 | 85 |
| 2000-08-17 | vs ANA | 117 | W 6-1 | 66-51 | 1 | 35,180 | Denny Neagle | Kent Mercker | Denny Neagle | Kent Mercker | | 653 | 563 | 90 |
| 2000-08-18 | vs ANA | 118 | L 8-9 | 66-52 | 1 | 37,503 | Roger Clemens | Ramon Ortiz | Shigetoshi Hasegawa | Mike Stanton | | 661 | 572 | 89 |
| 2000-08-19 | vs ANA | 119 | W 9-1 | 67-52 | 1 | 49,491 | Andy Pettitte | Brian Cooper | Andy Pettitte | Brian Cooper | | 670 | 573 | 97 |
| 2000-08-20 | vs ANA | 120 | L 4-5 | 67-53 | 1 | 50,048 | David Cone | Matt Wise | Matt Wise | Jeff Nelson | Shigetoshi Hasegawa | 674 | 578 | 96 |
| 2000-08-21 | vs TEX | 121 | W 12-3 | 68-53 | 1 | 16,310 | Orlando Hernandez | Brian Sikorski | Orlando Hernandez | Brian Sikorski | | 686 | 581 | 105 |
| 2000-08-22 | vs TEX | 122 | L 4-5 | 68-54 | 1 | 39,915 | Denny Neagle | Rick Helling | Tim Crabtree | Denny Neagle | John Wetteland | 690 | 586 | 104 |
| 2000-08-23 | vs TEX | 123 | W 10-9 | 69-54 | 1 | 33,081 | Roger Clemens | Kenny Rogers | Mariano Rivera | Tim Crabtree | | 700 | 595 | 105 |
| 2000-08-24 | vs TEX | 124 | W 8-7 | 70-54 | 1 | 44,578 | Andy Pettitte | Matt Perisho | Andy Pettitte | Matt Perisho | Mariano Rivera | 708 | 602 | 106 |
| 2000-08-25 | @ OAK | 125 | L 1-8 | 70-55 | 1 | 47,773 | David Cone | Kevin Appier | Kevin Appier | David Cone | | 709 | 610 | 99 |
| 2000-08-26 | @ OAK | 126 | W 10-6 | 71-55 | 1 | 43,099 | Orlando Hernandez | Mark Mulder | Orlando Hernandez | Mark Mulder | Mariano Rivera | 719 | 616 | 103 |
| 2000-08-27 | @ OAK | 127 | W 7-5 | 72-55 | 1 | 39,348 | Denny Neagle | Gil Heredia | Denny Neagle | Jim Mecir | Mariano Rivera | 726 | 621 | 105 |
| 2000-08-28 | @ SEA | 128 | W 9-1 | 73-55 | 1 | 45,077 | Roger Clemens | Paul Abbott | Roger Clemens | Paul Abbott | | 735 | 622 | 113 |
| 2000-08-29 | @ SEA | 129 | L 3-5 | 73-56 | 1 | 44,105 | Andy Pettitte | Jamie Moyer | Brett Tomko | Andy Pettitte | Kazuhiro Sasaki | 738 | 627 | 111 |
| 2000-08-30 | @ SEA | 130 | W 5-4 | 74-56 | 1 | 44,962 | David Cone | Aaron Sele | David Cone | Aaron Sele | Mariano Rivera | 743 | 631 | 112 |
| 2000-09-01 | vs MIN | 131 | W 4-2 | 75-56 | 1 | 38,294 | Orlando Hernandez | Brad Radke | Orlando Hernandez | Brad Radke | Mariano Rivera | 747 | 633 | 114 |
| 2000-09-02 | vs MIN | 132 | W 13-4 | 76-56 | 1 | 47,438 | Denny Neagle | Eric Milton | Denny Neagle | Eric Milton | Jason Grimsley | 760 | 637 | 123 |
| 2000-09-03 | vs MIN | 133 | L 1-2 | 76-57 | 1 | 42,365 | Roger Clemens | Matt Kinney | Eddie Guardado | Mariano Rivera | LaTroy Hawkins | 761 | 639 | 122 |
| 2000-09-04 | @ KCA | 134 | W 4-3 | 77-57 | 1 | 21,774 | Andy Pettitte | Mac Suzuki | Andy Pettitte | Mac Suzuki | Mariano Rivera | 765 | 642 | 123 |
| 2000-09-05 | @ KCA | 135 | W 10-5 | 78-57 | 1 | 15,025 | David Cone | Jeff Suppan | Dwight Gooden | Jeff Suppan | | 775 | 647 | 128 |
| 2000-09-06 | @ KCA | 136 | L 2-3 | 78-58 | 1 | 15,637 | Orlando Hernandez | Brian Meadows | Brian Meadows | Mike Stanton | | 777 | 650 | 127 |
| 2000-09-07 | @ KCA | 137 | W 7-3 | 79-58 | 1 | 20,933 | Denny Neagle | Dan Reichert | Denny Neagle | Ricky Bottalico | Mariano Rivera | 784 | 653 | 131 |
| 2000-09-08 | @ BOS | 138 | W 4-0 | 80-58 | 1 | 33,861 | Roger Clemens | Tomo Ohka | Roger Clemens | Tomo Ohka | | 788 | 653 | 135 |
| 2000-09-09 | @ BOS | 139 | W 5-3 | 81-58 | 1 | 33,355 | Andy Pettitte | Pedro Martinez | Andy Pettitte | Pedro Martinez | | 793 | 656 | 137 |
| 2000-09-10 | @ BOS | 140 | W 6-2 | 82-58 | 1 | 33,062 | Randy Keisler | Pete Schourek | Randy Keisler | Pete Schourek | Dwight Gooden | 799 | 658 | 141 |
| 2000-09-11 | vs BOS | 141 | L 0-4 | 82-59 | 1 | 40,326 | Orlando Hernandez | Rolando Arrojo | Rolando Arrojo | Orlando Hernandez | Derek Lowe | 799 | 662 | 137 |
| 2000-09-12 | vs TOR | 142 | W 10-2 | 83-59 | 1 | 30,370 | Denny Neagle | Joey Hamilton | Denny Neagle | Joey Hamilton | | 809 | 664 | 145 |
| 2000-09-13 | vs TOR | 143 | W 3-2 | 84-59 | 1 | 29,083 | Roger Clemens | Esteban Loaiza | Roger Clemens | Esteban Loaiza | Mariano Rivera | 812 | 666 | 146 |
| 2000-09-14 | vs TOR | 144 | L 2-3 | 84-60 | 1 | 35,040 | Andy Pettitte | David Wells | Billy Koch | Randy Choate | Kelvim Escobar | 814 | 669 | 145 |
| 2000-09-15 | vs CLE | 145 | L 1-11 | 84-61 | 1 | 48,443 | David Cone | Dave Burba | Dave Burba | David Cone | | 815 | 680 | 135 |
| 2000-09-16 | vs CLE | 146 | W 6-3 | 85-61 | 1 | 55,097 | Orlando Hernandez | Jason Bere | Orlando Hernandez | Jason Bere | | 821 | 683 | 138 |
| 2000-09-17 | vs CLE | 147 | L 4-15 | 85-62 | 1 | 50,174 | Denny Neagle | Chuck Finley | Chuck Finley | Denny Neagle | | 825 | 698 | 127 |
| 2000-09-18 | vs CLE | 148 | L 0-2 | 85-63 | 1 | 31,317 | Roger Clemens | Bartolo Colon | Bartolo Colon | Roger Clemens | | 825 | 700 | 125 |
| 2000-09-19 | @ TOR | 149 | L 3-16 | 85-64 | 1 | 28,908 | Andy Pettitte | Steve Trachsel | Steve Trachsel | Andy Pettitte | | 828 | 716 | 112 |
| 2000-09-20 | @ TOR | 150 | L 2-7 | 85-65 | 1 | 28,463 | David Cone | Esteban Loaiza | Esteban Loaiza | David Cone | | 830 | 723 | 107 |
| 2000-09-21 | @ TOR | 151 | L 1-3 | 85-66 | 1 | 30,074 | Orlando Hernandez | David Wells | David Wells | Orlando Hernandez | | 831 | 726 | 105 |
| 2000-09-22 | vs DET | 152 | L 6-9 | 85-67 | 1 | 37,092 | Denny Neagle | Hideo Nomo | Hideo Nomo | Denny Neagle | Todd Jones | 837 | 735 | 102 |
| 2000-09-23 | vs DET | 153 | W 13-8 | 86-67 | 1 | 40,029 | Roger Clemens | Dave Mlicki | Jeff Nelson | Willie Blair | Mariano Rivera | 850 | 743 | 107 |
| 2000-09-24 | vs DET | 154 | W 6-3 | 87-67 | 1 | 41,415 | Andy Pettitte | Jeff Weaver | Andy Pettitte | Jeff Weaver | Mariano Rivera | 856 | 746 | 110 |
| 2000-09-25 | vs DET | 155 | L 4-15 | 87-68 | 1 | 32,701 | Dwight Gooden | Steve Sparks | Steve Sparks | Dwight Gooden | | 860 | 761 | 99 |
| 2000-09-26 | @ TBA | 156 | L 1-2 | 87-69 | 1 | 19,469 | Orlando Hernandez | Albie Lopez | Roberto Hernandez | Jeff Nelson | | 861 | 763 | 98 |
| 2000-09-27 | @ TBA | 157 | L 1-11 | 87-70 | 1 | 18,863 | Denny Neagle | Cory Lidle | Cory Lidle | Denny Neagle | | 862 | 774 | 88 |
| 2000-09-28 | @ TBA | 158 | L 3-11 | 87-71 | 1 | 20,961 | Roger Clemens | Bryan Rekar | Bryan Rekar | Roger Clemens | | 865 | 785 | 80 |
| 2000-09-29 | @ BAL | 159 | L 2-13 | 87-72 | 1 | 47,674 | Andy Pettitte | Chuck McElroy | Chuck McElroy | Andy Pettitte | | 867 | 798 | 69 |
| 2000-09-30 | @ BAL | 160 | L 1-9 | 87-73 | 1 | 48,129 | David Cone | Mike Mussina | Mike Mussina | David Cone | | 868 | 807 | 61 |
| 2000-10-01 | @ BAL | 161 | L 3-7 | 87-74 | 1 | 47,831 | Orlando Hernandez | Jose Mercedes | Jose Mercedes | Orlando Hernandez | | 871 | 814 | 57 |