| 2005-04-05 | vs TEX | 1 | W 3-2 | 1-0 | 1 | 43,590 | Bartolo Colon | Ryan Drese | Bartolo Colon | Ryan Drese | Francisco Rodriguez | 3 | 2 | 1 |
| 2005-04-06 | vs TEX | 2 | L 2-3 | 1-1 | 3 | 35,077 | Jarrod Washburn | Kenny Rogers | Brian Shouse | Bret Prinz | | 5 | 5 | 0 |
| 2005-04-07 | vs TEX | 3 | W 7-6 | 2-1 | 2 | 35,169 | John Lackey | Chris Young | Scot Shields | Brian Shouse | | 12 | 11 | 1 |
| 2005-04-08 | vs KCA | 4 | L 2-6 | 2-2 | 3 | 39,167 | Paul Byrd | Denny Bautista | Denny Bautista | Paul Byrd | | 14 | 17 | -3 |
| 2005-04-09 | vs KCA | 5 | W 8-3 | 3-2 | 1 | 42,007 | Kevin Gregg | Jose Lima | Kevin Gregg | Jose Lima | | 22 | 20 | 2 |
| 2005-04-10 | vs KCA | 6 | L 3-8 | 3-3 | 3 | 40,689 | Bartolo Colon | Brian Anderson | Brian Anderson | Bartolo Colon | | 25 | 28 | -3 |
| 2005-04-11 | @ TEX | 7 | W 7-6 | 4-3 | 1 | 50,054 | Jarrod Washburn | Kenny Rogers | Scot Shields | R.A. Dickey | Francisco Rodriguez | 32 | 34 | -2 |
| 2005-04-12 | @ TEX | 8 | W 13-8 | 5-3 | 1 | 23,061 | John Lackey | Chris Young | John Lackey | Chris Young | Scot Shields | 45 | 42 | 3 |
| 2005-04-13 | @ TEX | 9 | L 5-7 | 5-4 | 1 | 21,625 | Paul Byrd | Chan Ho Park | Chan Ho Park | Paul Byrd | Francisco Cordero | 50 | 49 | 1 |
| 2005-04-15 | @ OAK | 10 | W 6-1 | 6-4 | 1 | 23,283 | Bartolo Colon | Barry Zito | Bartolo Colon | Barry Zito | | 56 | 50 | 6 |
| 2005-04-16 | @ OAK | 11 | L 0-1 | 6-5 | 1 | 25,280 | Jarrod Washburn | Rich Harden | Kiko Calero | Scot Shields | | 56 | 51 | 5 |
| 2005-04-17 | @ OAK | 12 | L 6-7 | 6-6 | 3 | 36,291 | John Lackey | Kirk Saarloos | Huston Street | John Lackey | Octavio Dotel | 62 | 58 | 4 |
| 2005-04-18 | vs SEA | 13 | W 6-1 | 7-6 | 2 | 39,638 | Paul Byrd | Aaron Sele | Paul Byrd | Aaron Sele | | 68 | 59 | 9 |
| 2005-04-19 | vs SEA | 14 | L 3-5 | 7-7 | 3 | 38,667 | Kevin Gregg | Jamie Moyer | Jamie Moyer | Kevin Gregg | Eddie Guardado | 71 | 64 | 7 |
| 2005-04-20 | vs CLE | 15 | W 2-0 | 8-7 | 2 | 42,531 | Bartolo Colon | Jake Westbrook | Bartolo Colon | Jake Westbrook | Francisco Rodriguez | 73 | 64 | 9 |
| 2005-04-21 | vs CLE | 16 | W 6-5 | 9-7 | 1 | 39,673 | Jarrod Washburn | Kevin Millwood | Francisco Rodriguez | Jason Davis | | 79 | 69 | 10 |
| 2005-04-22 | vs OAK | 17 | L 3-4 | 9-8 | 2 | 43,810 | John Lackey | Kirk Saarloos | Keiichi Yabu | Francisco Rodriguez | Octavio Dotel | 82 | 73 | 9 |
| 2005-04-23 | vs OAK | 18 | W 9-5 | 10-8 | 1 | 43,880 | Paul Byrd | Dan Haren | Jake Woods | Dan Haren | | 91 | 78 | 13 |
| 2005-04-24 | vs OAK | 19 | W 1-0 | 11-8 | 1 | 43,915 | Kelvim Escobar | Joe Blanton | Scot Shields | Joe Blanton | Francisco Rodriguez | 92 | 78 | 14 |
| 2005-04-26 | @ NYA | 20 | L 4-12 | 11-9 | 1 | 36,328 | Bartolo Colon | Carl Pavano | Carl Pavano | Bartolo Colon | | 96 | 90 | 6 |
| 2005-04-27 | @ NYA | 21 | W 5-1 | 12-9 | 1 | 37,934 | Jarrod Washburn | Mike Mussina | Jarrod Washburn | Mike Mussina | | 101 | 91 | 10 |
| 2005-04-28 | @ NYA | 22 | W 3-1 | 13-9 | 1 | 51,951 | John Lackey | Kevin Brown | John Lackey | Kevin Brown | Francisco Rodriguez | 104 | 92 | 12 |
| 2005-04-29 | @ MIN | 23 | L 4-7 | 13-10 | 1 | 29,866 | Paul Byrd | Carlos Silva | Carlos Silva | Paul Byrd | Joe Nathan | 108 | 99 | 9 |
| 2005-04-30 | @ MIN | 24 | L 2-4 | 13-11 | 1 | 31,576 | Kelvim Escobar | Brad Radke | Brad Radke | Kelvim Escobar | Joe Nathan | 110 | 103 | 7 |
| 2005-05-01 | @ MIN | 25 | W 2-1 | 14-11 | 1 | 30,837 | Bartolo Colon | Johan Santana | Bartolo Colon | Johan Santana | Francisco Rodriguez | 112 | 104 | 8 |
| 2005-05-02 | @ SEA | 26 | W 5-0 | 15-11 | 1 | 24,184 | Jarrod Washburn | Ryan Franklin | Jarrod Washburn | Ryan Franklin | | 117 | 104 | 13 |
| 2005-05-03 | @ SEA | 27 | W 5-2 | 16-11 | 1 | 29,917 | John Lackey | Gil Meche | John Lackey | Gil Meche | Scot Shields | 122 | 106 | 16 |
| 2005-05-04 | @ SEA | 28 | W 5-2 | 17-11 | 1 | 26,303 | Paul Byrd | Aaron Sele | Paul Byrd | Aaron Sele | Francisco Rodriguez | 127 | 108 | 19 |
| 2005-05-06 | vs DET | 29 | W 4-3 | 18-11 | 1 | 44,022 | Kelvim Escobar | Wil Ledezma | Kelvim Escobar | Wil Ledezma | Francisco Rodriguez | 131 | 111 | 20 |
| 2005-05-07 | vs DET | 30 | L 1-2 | 18-12 | 1 | 43,876 | Bartolo Colon | Jeremy Bonderman | Jeremy Bonderman | Bartolo Colon | Troy Percival | 132 | 113 | 19 |
| 2005-05-08 | vs DET | 31 | L 1-10 | 18-13 | 1 | 43,587 | Jarrod Washburn | Mike Maroth | Mike Maroth | Jarrod Washburn | | 133 | 123 | 10 |
| 2005-05-09 | vs CLE | 32 | L 0-3 | 18-14 | 1 | 36,763 | John Lackey | Kevin Millwood | Kevin Millwood | John Lackey | Bob Wickman | 133 | 126 | 7 |
| 2005-05-10 | vs CLE | 33 | W 5-4 | 19-14 | 1 | 38,320 | Paul Byrd | CC Sabathia | Paul Byrd | CC Sabathia | Francisco Rodriguez | 138 | 130 | 8 |
| 2005-05-11 | vs CLE | 34 | L 3-9 | 19-15 | 1 | 35,508 | Kelvim Escobar | Cliff Lee | Cliff Lee | Kelvim Escobar | | 141 | 139 | 2 |
| 2005-05-14 | @ DET | 35 | W 4-2 | 20-16 | 1 | 0 | Bartolo Colon | Jeremy Bonderman | Brendan Donnelly | Jamie Walker | Francisco Rodriguez | 145 | 141 | 4 |
| 2005-05-14 | @ DET | 36 | L 2-3 | 20-16 | 1 | 33,380 | Jarrod Washburn | Mike Maroth | Mike Maroth | Jarrod Washburn | Ugueth Urbina | 147 | 144 | 3 |
| 2005-05-15 | @ DET | 37 | W 9-3 | 21-16 | 1 | 23,107 | John Lackey | Nate Robertson | John Lackey | Nate Robertson | | 156 | 147 | 9 |
| 2005-05-16 | @ CLE | 38 | W 3-1 | 22-16 | 1 | 13,729 | Paul Byrd | Cliff Lee | Paul Byrd | Cliff Lee | Scot Shields | 159 | 148 | 11 |
| 2005-05-17 | @ CLE | 39 | L 5-13 | 22-17 | 1 | 15,033 | Ervin Santana | Scott Elarton | Scott Elarton | Ervin Santana | | 164 | 161 | 3 |
| 2005-05-18 | @ CLE | 40 | W 2-1 | 23-17 | 1 | 19,030 | Bartolo Colon | Jake Westbrook | Bartolo Colon | Jake Westbrook | Scot Shields | 166 | 162 | 4 |
| 2005-05-20 | @ LAN | 41 | W 9-0 | 24-17 | 1 | 54,543 | Jarrod Washburn | Scott Erickson | Jarrod Washburn | Scott Erickson | | 175 | 162 | 13 |
| 2005-05-21 | @ LAN | 42 | W 3-1 | 25-17 | 1 | 53,631 | John Lackey | Brad Penny | Brendan Donnelly | Giovanni Carrara | Scot Shields | 178 | 163 | 15 |
| 2005-05-22 | @ LAN | 43 | L 2-6 | 25-18 | 1 | 53,839 | Paul Byrd | Derek Lowe | Derek Lowe | Paul Byrd | | 180 | 169 | 11 |
| 2005-05-23 | vs CHA | 44 | W 4-0 | 26-18 | 1 | 40,991 | Ervin Santana | Jon Garland | Ervin Santana | Jon Garland | | 184 | 169 | 15 |
| 2005-05-24 | vs CHA | 45 | L 1-2 | 26-19 | 1 | 35,182 | Bartolo Colon | Mark Buehrle | Damaso Marte | Esteban Yan | | 185 | 171 | 14 |
| 2005-05-25 | vs CHA | 46 | L 2-4 | 26-20 | 2 | 42,716 | Jarrod Washburn | Freddy Garcia | Freddy Garcia | Jarrod Washburn | Dustin Hermanson | 187 | 175 | 12 |
| 2005-05-26 | vs CHA | 47 | W 3-2 | 27-20 | 2 | 39,128 | John Lackey | Jose Contreras | John Lackey | Jose Contreras | Scot Shields | 190 | 177 | 13 |
| 2005-05-27 | vs KCA | 48 | W 9-8 | 28-20 | 2 | 40,834 | Paul Byrd | D.J. Carrasco | Scot Shields | Mike MacDougal | | 199 | 185 | 14 |
| 2005-05-28 | vs KCA | 49 | W 14-1 | 29-20 | 1 | 43,929 | Kelvim Escobar | Ryan Jensen | Kelvim Escobar | Ryan Jensen | Chris Bootcheck | 213 | 186 | 27 |
| 2005-05-29 | vs KCA | 50 | W 7-6 | 30-20 | 1 | 42,345 | Bartolo Colon | Runelvys Hernandez | Bartolo Colon | Runelvys Hernandez | Scot Shields | 220 | 192 | 28 |
| 2005-05-30 | @ CHA | 51 | L 4-5 | 30-21 | 2 | 38,685 | Jarrod Washburn | Mark Buehrle | Cliff Politte | Scot Shields | | 224 | 197 | 27 |
| 2005-05-31 | @ CHA | 52 | L 4-5 | 30-22 | 2 | 19,864 | John Lackey | Freddy Garcia | Cliff Politte | Brendan Donnelly | | 228 | 202 | 26 |
| 2005-06-01 | @ CHA | 53 | W 10-7 | 31-22 | 2 | 19,393 | Paul Byrd | Jose Contreras | Paul Byrd | Kevin Walker | | 238 | 209 | 29 |
| 2005-06-03 | @ BOS | 54 | L 4-7 | 31-23 | 1 | 35,328 | Kelvim Escobar | David Wells | Mike Myers | Scot Shields | Keith Foulke | 242 | 216 | 26 |
| 2005-06-04 | @ BOS | 55 | W 13-6 | 32-23 | 1 | 34,754 | Bartolo Colon | Bronson Arroyo | Bartolo Colon | Alan Embree | | 255 | 222 | 33 |
| 2005-06-05 | @ BOS | 56 | L 3-6 | 32-24 | 2 | 35,008 | Jarrod Washburn | Wade Miller | Mike Myers | Jake Woods | Keith Foulke | 258 | 228 | 30 |
| 2005-06-06 | @ ATL | 57 | W 4-2 | 33-24 | 2 | 23,104 | John Lackey | John Smoltz | Brendan Donnelly | John Smoltz | Francisco Rodriguez | 262 | 230 | 32 |
| 2005-06-07 | @ ATL | 58 | L 2-3 | 33-25 | 2 | 25,276 | Paul Byrd | Horacio Ramirez | Horacio Ramirez | Paul Byrd | Chris Reitsma | 264 | 233 | 31 |
| 2005-06-08 | @ ATL | 59 | W 8-4 | 34-25 | 1 | 27,747 | Kelvim Escobar | Tim Hudson | Brendan Donnelly | John Foster | | 272 | 237 | 35 |
| 2005-06-10 | @ NYN | 60 | W 12-2 | 35-25 | 1 | 31,131 | Bartolo Colon | Kazuhisa Ishii | Bartolo Colon | Kazuhisa Ishii | | 284 | 239 | 45 |
| 2005-06-11 | @ NYN | 61 | L 3-5 | 35-26 | 1 | 33,889 | Jarrod Washburn | Kris Benson | Braden Looper | Brendan Donnelly | | 287 | 244 | 43 |
| 2005-06-12 | @ NYN | 62 | W 4-3 | 36-26 | 1 | 43,582 | John Lackey | Pedro Martinez | Scot Shields | Braden Looper | Francisco Rodriguez | 291 | 247 | 44 |
| 2005-06-13 | vs WAS | 63 | W 11-1 | 37-26 | 1 | 40,790 | Paul Byrd | Esteban Loaiza | Paul Byrd | Esteban Loaiza | | 302 | 248 | 54 |
| 2005-06-14 | vs WAS | 64 | L 3-6 | 37-27 | 1 | 43,874 | Ervin Santana | Livan Hernandez | Gary Majewski | Scot Shields | Chad Cordero | 305 | 254 | 51 |
| 2005-06-15 | vs WAS | 65 | L 0-1 | 37-28 | 1 | 43,505 | Bartolo Colon | Ryan Drese | Ryan Drese | Bartolo Colon | Chad Cordero | 305 | 255 | 50 |
| 2005-06-17 | vs FLO | 66 | W 3-2 | 38-28 | 1 | 43,767 | Jarrod Washburn | Brian Moehler | Scot Shields | Jim Mecir | | 308 | 257 | 51 |
| 2005-06-18 | vs FLO | 67 | W 2-1 | 39-28 | 1 | 43,833 | John Lackey | Dontrelle Willis | Francisco Rodriguez | Todd Jones | | 310 | 258 | 52 |
| 2005-06-19 | vs FLO | 68 | L 5-7 | 39-29 | 1 | 43,788 | Ervin Santana | Al Leiter | Al Leiter | Ervin Santana | Todd Jones | 315 | 265 | 50 |
| 2005-06-20 | vs TEX | 69 | W 5-1 | 40-29 | 1 | 41,007 | Paul Byrd | Chris Young | Paul Byrd | Chris Young | | 320 | 266 | 54 |
| 2005-06-21 | vs TEX | 70 | W 8-6 | 41-29 | 1 | 43,025 | Bartolo Colon | Chan Ho Park | Bartolo Colon | Chan Ho Park | | 328 | 272 | 56 |
| 2005-06-22 | vs TEX | 71 | W 6-0 | 42-29 | 1 | 41,763 | Jarrod Washburn | Kenny Rogers | Jarrod Washburn | Kenny Rogers | | 334 | 272 | 62 |
| 2005-06-24 | vs LAN | 72 | W 7-0 | 43-29 | 1 | 44,056 | John Lackey | Jeff Weaver | John Lackey | Jeff Weaver | | 341 | 272 | 69 |
| 2005-06-25 | vs LAN | 73 | W 3-1 | 44-29 | 1 | 44,107 | Ervin Santana | Brad Penny | Ervin Santana | Brad Penny | Francisco Rodriguez | 344 | 273 | 71 |
| 2005-06-26 | vs LAN | 74 | W 5-3 | 45-29 | 1 | 44,029 | Paul Byrd | Derek Lowe | Brendan Donnelly | Kelly Wunsch | Francisco Rodriguez | 349 | 276 | 73 |
| 2005-06-27 | @ TEX | 75 | W 13-3 | 46-29 | 1 | 34,471 | Bartolo Colon | C.J. Wilson | Bartolo Colon | C.J. Wilson | | 362 | 279 | 83 |
| 2005-06-28 | @ TEX | 76 | W 5-1 | 47-29 | 1 | 27,159 | Jarrod Washburn | John Wasdin | Brendan Donnelly | Kameron Loe | | 367 | 280 | 87 |
| 2005-06-29 | @ TEX | 77 | L 6-7 | 47-30 | 1 | 30,112 | John Lackey | Ricardo Rodriguez | Kameron Loe | Scot Shields | | 373 | 287 | 86 |
| 2005-06-30 | @ TEX | 78 | L 5-18 | 47-31 | 1 | 27,466 | Ervin Santana | Chris Young | Chris Young | Ervin Santana | | 378 | 305 | 73 |
| 2005-07-01 | @ KCA | 79 | W 5-0 | 48-31 | 1 | 17,893 | Paul Byrd | Runelvys Hernandez | Paul Byrd | Runelvys Hernandez | | 383 | 305 | 78 |
| 2005-07-02 | @ KCA | 80 | W 5-3 | 49-31 | 1 | 16,051 | Bartolo Colon | Jose Lima | Bartolo Colon | Jose Lima | Francisco Rodriguez | 388 | 308 | 80 |
| 2005-07-03 | @ KCA | 81 | W 5-0 | 50-31 | 1 | 14,872 | Jarrod Washburn | Zack Greinke | Jarrod Washburn | Zack Greinke | | 393 | 308 | 85 |
| 2005-07-04 | vs MIN | 82 | L 5-7 | 50-32 | 1 | 44,008 | John Lackey | Carlos Silva | Carlos Silva | John Lackey | Joe Nathan | 398 | 315 | 83 |
| 2005-07-05 | vs MIN | 83 | W 2-1 | 51-32 | 1 | 42,335 | Ervin Santana | Scott Baker | Ervin Santana | Scott Baker | Francisco Rodriguez | 400 | 316 | 84 |
| 2005-07-06 | vs MIN | 84 | W 7-6 | 52-32 | 1 | 41,534 | Paul Byrd | Johan Santana | Joel Peralta | Johan Santana | Francisco Rodriguez | 407 | 322 | 85 |
| 2005-07-07 | vs SEA | 85 | L 2-10 | 52-33 | 1 | 43,747 | Bartolo Colon | Joel Pineiro | Joel Pineiro | Bartolo Colon | | 409 | 332 | 77 |
| 2005-07-08 | vs SEA | 86 | L 4-10 | 52-34 | 1 | 43,853 | Jarrod Washburn | Jamie Moyer | Jamie Moyer | Jarrod Washburn | | 413 | 342 | 71 |
| 2005-07-09 | vs SEA | 87 | L 3-6 | 52-35 | 1 | 44,012 | John Lackey | Ryan Franklin | Ryan Franklin | John Lackey | | 416 | 348 | 68 |
| 2005-07-10 | vs SEA | 88 | L 4-7 | 52-36 | 1 | 41,657 | Ervin Santana | Gil Meche | Gil Meche | Ervin Santana | Eddie Guardado | 420 | 355 | 65 |
| 2005-07-14 | @ MIN | 89 | W 3-2 | 53-36 | 1 | 21,979 | Jarrod Washburn | Kyle Lohse | Jarrod Washburn | Kyle Lohse | Francisco Rodriguez | 423 | 357 | 66 |
| 2005-07-15 | @ MIN | 90 | W 3-2 | 54-36 | 1 | 25,920 | Paul Byrd | Brad Radke | Paul Byrd | Brad Radke | Francisco Rodriguez | 426 | 359 | 67 |
| 2005-07-16 | @ MIN | 91 | L 4-5 | 54-37 | 1 | 34,009 | Bartolo Colon | Johan Santana | Johan Santana | Bartolo Colon | Joe Nathan | 430 | 364 | 66 |
| 2005-07-17 | @ MIN | 92 | W 2-1 | 55-37 | 1 | 30,367 | John Lackey | Joe Mays | John Lackey | Joe Mays | Francisco Rodriguez | 432 | 365 | 67 |
| 2005-07-18 | vs OAK | 93 | W 5-2 | 56-37 | 1 | 40,546 | Ervin Santana | Kirk Saarloos | Ervin Santana | Kirk Saarloos | Francisco Rodriguez | 437 | 367 | 70 |
| 2005-07-19 | vs OAK | 94 | L 1-3 | 56-38 | 1 | 42,155 | Jarrod Washburn | Rich Harden | Rich Harden | Jarrod Washburn | Huston Street | 438 | 370 | 68 |
| 2005-07-20 | vs OAK | 95 | L 0-3 | 56-39 | 1 | 42,285 | Paul Byrd | Barry Zito | Barry Zito | Paul Byrd | Huston Street | 438 | 373 | 65 |
| 2005-07-21 | vs NYA | 96 | W 6-5 | 57-39 | 1 | 44,109 | Bartolo Colon | Randy Johnson | Bartolo Colon | Tom Gordon | Francisco Rodriguez | 444 | 378 | 66 |
| 2005-07-22 | vs NYA | 97 | W 6-3 | 58-39 | 1 | 44,043 | John Lackey | Al Leiter | John Lackey | Al Leiter | Francisco Rodriguez | 450 | 381 | 69 |
| 2005-07-23 | vs NYA | 98 | W 8-6 | 59-39 | 1 | 44,035 | Ervin Santana | Kevin Brown | Ervin Santana | Kevin Brown | Francisco Rodriguez | 458 | 387 | 71 |
| 2005-07-24 | vs NYA | 99 | L 1-4 | 59-40 | 1 | 44,032 | Jarrod Washburn | Mike Mussina | Mike Mussina | Jarrod Washburn | Mariano Rivera | 459 | 391 | 68 |
| 2005-07-26 | @ TOR | 100 | L 0-8 | 59-41 | 1 | 18,754 | Paul Byrd | Gustavo Chacin | Gustavo Chacin | Paul Byrd | | 459 | 399 | 60 |
| 2005-07-27 | @ TOR | 101 | L 2-3 | 59-42 | 1 | 18,998 | Bartolo Colon | Josh Towers | Miguel Batista | Brendan Donnelly | | 461 | 402 | 59 |
| 2005-07-28 | @ TOR | 102 | L 1-2 | 59-43 | 1 | 19,706 | John Lackey | David Bush | Pete Walker | Scot Shields | | 462 | 404 | 58 |
| 2005-07-29 | @ NYA | 103 | W 4-1 | 60-43 | 1 | 54,025 | Ervin Santana | Mike Mussina | Ervin Santana | Mike Mussina | Francisco Rodriguez | 466 | 405 | 61 |
| 2005-07-30 | @ NYA | 104 | L 7-8 | 60-44 | 1 | 54,220 | Paul Byrd | Shawn Chacon | Mariano Rivera | Francisco Rodriguez | | 473 | 413 | 60 |
| 2005-07-31 | @ NYA | 105 | L 7-8 | 60-45 | 1 | 53,653 | Chris Bootcheck | Randy Johnson | Tom Gordon | Kevin Gregg | | 480 | 421 | 59 |
| 2005-08-02 | vs BAL | 106 | W 10-1 | 61-45 | 1 | 43,643 | Bartolo Colon | Sidney Ponson | Bartolo Colon | Sidney Ponson | | 490 | 422 | 68 |
| 2005-08-03 | vs BAL | 107 | W 8-4 | 62-45 | 1 | 43,749 | John Lackey | Erik Bedard | John Lackey | Erik Bedard | | 498 | 426 | 72 |
| 2005-08-04 | vs BAL | 108 | L 1-4 | 62-46 | 1 | 43,877 | Ervin Santana | Rodrigo Lopez | Rodrigo Lopez | Ervin Santana | B.J. Ryan | 499 | 430 | 69 |
| 2005-08-05 | vs TBA | 109 | W 5-4 | 63-46 | 1 | 43,873 | Paul Byrd | Doug Waechter | Scot Shields | Doug Waechter | Francisco Rodriguez | 504 | 434 | 70 |
| 2005-08-06 | vs TBA | 110 | L 4-6 | 63-47 | 2 | 43,909 | Chris Bootcheck | Mark Hendrickson | Mark Hendrickson | Chris Bootcheck | Danys Baez | 508 | 440 | 68 |
| 2005-08-07 | vs TBA | 111 | W 10-4 | 64-47 | 2 | 43,730 | Bartolo Colon | Seth McClung | Bartolo Colon | Seth McClung | | 518 | 444 | 74 |
| 2005-08-09 | @ OAK | 112 | W 9-2 | 65-47 | 1 | 40,774 | John Lackey | Rich Harden | John Lackey | Rich Harden | | 527 | 446 | 81 |
| 2005-08-10 | @ OAK | 113 | L 3-4 | 65-48 | 2 | 45,131 | Ervin Santana | Barry Zito | Justin Duchscherer | Scot Shields | Huston Street | 530 | 450 | 80 |
| 2005-08-11 | @ OAK | 114 | L 4-5 | 65-49 | 2 | 31,471 | Paul Byrd | Joe Blanton | Justin Duchscherer | Scot Shields | | 534 | 455 | 79 |
| 2005-08-12 | @ SEA | 115 | W 9-4 | 66-49 | 2 | 37,585 | Jarrod Washburn | Jamie Moyer | Brendan Donnelly | J.J. Putz | | 543 | 459 | 84 |
| 2005-08-13 | @ SEA | 116 | W 9-1 | 67-49 | 2 | 42,500 | Bartolo Colon | Ryan Franklin | Bartolo Colon | Ryan Franklin | | 552 | 460 | 92 |
| 2005-08-14 | @ SEA | 117 | W 7-6 | 68-49 | 1 | 38,468 | John Lackey | Gil Meche | Brendan Donnelly | George Sherrill | Francisco Rodriguez | 559 | 466 | 93 |
| 2005-08-15 | vs TOR | 118 | W 5-4 | 69-49 | 1 | 38,936 | Ervin Santana | Gustavo Chacin | Scot Shields | Pete Walker | | 564 | 470 | 94 |
| 2005-08-16 | vs TOR | 119 | L 3-4 | 69-50 | 1 | 42,468 | Joe Saunders | Scott Downs | Brandon League | Francisco Rodriguez | Miguel Batista | 567 | 474 | 93 |
| 2005-08-17 | vs TOR | 120 | L 1-4 | 69-51 | 1 | 43,026 | Jarrod Washburn | Josh Towers | Josh Towers | Jarrod Washburn | Miguel Batista | 568 | 478 | 90 |
| 2005-08-18 | vs BOS | 121 | W 13-4 | 70-51 | 1 | 44,050 | Bartolo Colon | Tim Wakefield | Bartolo Colon | Tim Wakefield | | 581 | 482 | 99 |
| 2005-08-19 | vs BOS | 122 | L 3-4 | 70-52 | 1 | 43,896 | John Lackey | Matt Clement | Curt Schilling | Scot Shields | | 584 | 486 | 98 |
| 2005-08-20 | vs BOS | 123 | W 4-2 | 71-52 | 1 | 44,014 | Ervin Santana | Bronson Arroyo | Ervin Santana | Bronson Arroyo | Francisco Rodriguez | 588 | 488 | 100 |
| 2005-08-21 | vs BOS | 124 | L 1-5 | 71-53 | 1 | 44,022 | Paul Byrd | Jonathan Papelbon | Mike Timlin | Paul Byrd | | 589 | 493 | 96 |
| 2005-08-23 | @ BAL | 125 | W 7-6 | 72-53 | 1 | 31,768 | Jarrod Washburn | Eric DuBose | Jarrod Washburn | Eric DuBose | Francisco Rodriguez | 596 | 499 | 97 |
| 2005-08-24 | @ BAL | 126 | W 3-1 | 73-53 | 1 | 27,586 | Bartolo Colon | Erik Bedard | Bartolo Colon | Erik Bedard | Francisco Rodriguez | 599 | 500 | 99 |
| 2005-08-25 | @ BAL | 127 | L 0-2 | 73-54 | 1 | 26,832 | John Lackey | Rodrigo Lopez | Rodrigo Lopez | John Lackey | B.J. Ryan | 599 | 502 | 97 |
| 2005-08-26 | @ TBA | 128 | L 8-12 | 73-55 | 1 | 13,039 | Ervin Santana | Casey Fossum | Casey Fossum | Ervin Santana | | 607 | 514 | 93 |
| 2005-08-27 | @ TBA | 129 | L 3-6 | 73-56 | 1 | 12,445 | Paul Byrd | Doug Waechter | Doug Waechter | Paul Byrd | Danys Baez | 610 | 520 | 90 |
| 2005-08-28 | @ TBA | 130 | L 1-2 | 73-57 | 2 | 13,703 | Jarrod Washburn | Mark Hendrickson | Mark Hendrickson | Jarrod Washburn | Danys Baez | 611 | 522 | 89 |
| 2005-08-30 | vs OAK | 131 | L 1-2 | 73-58 | 2 | 42,176 | Bartolo Colon | Barry Zito | Kiko Calero | Francisco Rodriguez | Huston Street | 612 | 524 | 88 |
| 2005-08-31 | vs OAK | 132 | W 2-1 | 74-58 | 2 | 43,501 | John Lackey | Joe Blanton | John Lackey | Joe Blanton | Francisco Rodriguez | 614 | 525 | 89 |
| 2005-09-01 | vs OAK | 133 | W 3-0 | 75-58 | 2 | 41,632 | Ervin Santana | Joe Kennedy | Ervin Santana | Joe Kennedy | Francisco Rodriguez | 617 | 525 | 92 |
| 2005-09-02 | vs SEA | 134 | W 4-1 | 76-58 | 2 | 42,604 | Paul Byrd | Jamie Moyer | Paul Byrd | Jamie Moyer | Francisco Rodriguez | 621 | 526 | 95 |
| 2005-09-03 | vs SEA | 135 | L 3-6 | 76-59 | 2 | 43,819 | Jarrod Washburn | Ryan Franklin | J.J. Putz | Scot Shields | | 624 | 532 | 92 |
| 2005-09-04 | vs SEA | 136 | W 5-3 | 77-59 | 1 | 43,757 | Bartolo Colon | Jeff Harris | Bartolo Colon | Jeff Harris | Francisco Rodriguez | 629 | 535 | 94 |
| 2005-09-06 | @ BOS | 137 | L 2-3 | 77-60 | 1 | 35,061 | John Lackey | Tim Wakefield | Tim Wakefield | Scot Shields | | 631 | 538 | 93 |
| 2005-09-07 | @ BOS | 138 | L 3-6 | 77-61 | 1 | 35,423 | Ervin Santana | Bronson Arroyo | Bronson Arroyo | Ervin Santana | Mike Timlin | 634 | 544 | 90 |
| 2005-09-08 | @ BOS | 139 | W 3-0 | 78-61 | 1 | 35,351 | Paul Byrd | Matt Clement | Paul Byrd | Matt Clement | Francisco Rodriguez | 637 | 544 | 93 |
| 2005-09-09 | @ CHA | 140 | W 6-5 | 79-61 | 1 | 28,059 | Jarrod Washburn | Mark Buehrle | Brendan Donnelly | Dustin Hermanson | Francisco Rodriguez | 643 | 549 | 94 |
| 2005-09-10 | @ CHA | 141 | W 10-5 | 80-61 | 1 | 26,538 | Bartolo Colon | Jon Garland | Bartolo Colon | Jon Garland | | 653 | 554 | 99 |
| 2005-09-11 | @ CHA | 142 | W 6-1 | 81-61 | 1 | 29,321 | John Lackey | Orlando Hernandez | John Lackey | Orlando Hernandez | | 659 | 555 | 104 |
| 2005-09-12 | @ SEA | 143 | L 1-8 | 81-62 | 1 | 27,952 | Ervin Santana | Joel Pineiro | Joel Pineiro | Ervin Santana | | 660 | 563 | 97 |
| 2005-09-13 | @ SEA | 144 | L 1-2 | 81-63 | 1 | 28,813 | Paul Byrd | Ryan Franklin | J.J. Putz | Paul Byrd | | 661 | 565 | 96 |
| 2005-09-14 | @ SEA | 145 | L 9-10 | 81-64 | 1 | 23,397 | Joe Saunders | Jamie Moyer | Eddie Guardado | Francisco Rodriguez | | 670 | 575 | 95 |
| 2005-09-15 | vs DET | 146 | L 6-8 | 81-65 | 2 | 41,962 | Bartolo Colon | Mike Maroth | Mike Maroth | Bartolo Colon | Craig Dingman | 676 | 583 | 93 |
| 2005-09-16 | vs DET | 147 | W 7-6 | 82-65 | 1 | 43,144 | John Lackey | Jason Johnson | Kelvim Escobar | Vic Darensbourg | | 683 | 589 | 94 |
| 2005-09-17 | vs DET | 148 | W 3-1 | 83-65 | 1 | 43,831 | Ervin Santana | Roman Colon | Ervin Santana | Chris Spurling | Francisco Rodriguez | 686 | 590 | 96 |
| 2005-09-18 | vs DET | 149 | W 5-3 | 84-65 | 1 | 43,076 | Paul Byrd | Matt Ginter | Paul Byrd | Matt Ginter | Francisco Rodriguez | 691 | 593 | 98 |
| 2005-09-20 | vs TEX | 150 | W 2-1 | 85-65 | 1 | 36,170 | Bartolo Colon | Juan Dominguez | Bartolo Colon | Juan Dominguez | Francisco Rodriguez | 693 | 594 | 99 |
| 2005-09-21 | vs TEX | 151 | W 6-5 | 86-65 | 1 | 37,776 | John Lackey | Kameron Loe | Esteban Yan | Scott Feldman | Francisco Rodriguez | 699 | 599 | 100 |
| 2005-09-22 | vs TEX | 152 | W 7-4 | 87-65 | 1 | 36,588 | Ervin Santana | Chris Young | Ervin Santana | Edinson Volquez | Kelvim Escobar | 706 | 603 | 103 |
| 2005-09-23 | vs TBA | 153 | W 7-5 | 88-65 | 1 | 42,421 | Paul Byrd | Casey Fossum | Scot Shields | Joe Borowski | Francisco Rodriguez | 713 | 608 | 105 |
| 2005-09-24 | vs TBA | 154 | W 7-3 | 89-65 | 1 | 42,344 | Jarrod Washburn | Doug Waechter | Jarrod Washburn | Doug Waechter | | 720 | 611 | 109 |
| 2005-09-25 | vs TBA | 155 | L 4-8 | 89-66 | 1 | 41,733 | Bartolo Colon | Mark Hendrickson | Mark Hendrickson | Bartolo Colon | | 724 | 619 | 105 |
| 2005-09-26 | @ OAK | 156 | W 4-3 | 90-66 | 1 | 19,347 | John Lackey | Joe Blanton | John Lackey | Joe Blanton | Francisco Rodriguez | 728 | 622 | 106 |
| 2005-09-27 | @ OAK | 157 | W 4-3 | 91-66 | 1 | 18,416 | Ervin Santana | Joe Kennedy | Ervin Santana | Joe Kennedy | Francisco Rodriguez | 732 | 625 | 107 |
| 2005-09-28 | @ OAK | 158 | L 1-6 | 91-67 | 1 | 34,562 | Paul Byrd | Dan Haren | Dan Haren | Paul Byrd | | 733 | 631 | 102 |
| 2005-09-29 | @ OAK | 159 | W 7-1 | 92-67 | 1 | 21,957 | Bartolo Colon | Barry Zito | Bartolo Colon | Barry Zito | | 740 | 632 | 108 |
| 2005-09-30 | @ TEX | 160 | W 7-1 | 93-67 | 1 | 38,187 | John Lackey | R.A. Dickey | John Lackey | R.A. Dickey | | 747 | 633 | 114 |
| 2005-10-01 | @ TEX | 161 | W 7-6 | 94-67 | 1 | 48,174 | Jarrod Washburn | Juan Dominguez | Scot Shields | Juan Dominguez | Francisco Rodriguez | 754 | 639 | 115 |
| 2005-10-02 | @ TEX | 162 | W 7-4 | 95-67 | 1 | 38,334 | Ervin Santana | Kameron Loe | Ervin Santana | Kameron Loe | Francisco Rodriguez | 761 | 643 | 118 |