| 2012-04-06 | vs NYA | 1 | W 7-6 | 1-0 | 2 | 34,078 | James Shields | CC Sabathia | Fernando Rodney | Mariano Rivera | | 7 | 6 | 1 |
| 2012-04-07 | vs NYA | 2 | W 8-6 | 2-0 | 2 | 34,078 | David Price | Hiroki Kuroda | David Price | Hiroki Kuroda | Fernando Rodney | 15 | 12 | 3 |
| 2012-04-08 | vs NYA | 3 | W 3-0 | 3-0 | 2 | 30,413 | Jeremy Hellickson | Phil Hughes | Jeremy Hellickson | Phil Hughes | Fernando Rodney | 18 | 12 | 6 |
| 2012-04-10 | @ DET | 4 | L 2-5 | 3-1 | 1 | 22,574 | Matt Moore | Rick Porcello | Phil Coke | Jake McGee | Jose Valverde | 20 | 17 | 3 |
| 2012-04-11 | @ DET | 5 | W 4-2 | 4-1 | 1 | 28,180 | James Shields | Justin Verlander | James Shields | Justin Verlander | Fernando Rodney | 24 | 19 | 5 |
| 2012-04-12 | @ DET | 6 | L 2-7 | 4-2 | 1 | 30,288 | Jeff Niemann | Drew Smyly | Collin Balester | Jeff Niemann | | 26 | 26 | 0 |
| 2012-04-13 | @ BOS | 7 | W 2-12 | 5-2 | 1 | 37,032 | David Price | Josh Beckett | Josh Beckett | David Price | | 28 | 38 | -10 |
| 2012-04-14 | @ BOS | 8 | W 5-13 | 6-2 | 1 | 38,024 | Jeremy Hellickson | Clay Buchholz | Clay Buchholz | Burke Badenhop | | 33 | 51 | -18 |
| 2012-04-15 | @ BOS | 9 | L 4-6 | 6-3 | 1 | 38,024 | Matt Moore | Felix Doubront | Vicente Padilla | Matt Moore | Alfredo Aceves | 37 | 57 | -20 |
| 2012-04-16 | @ BOS | 10 | W 1-0 | 7-3 | 1 | 38,108 | James Shields | Daniel Bard | James Shields | Daniel Bard | Fernando Rodney | 38 | 57 | -19 |
| 2012-04-17 | @ TOR | 11 | L 3-7 | 7-4 | 1 | 15,331 | Jeff Niemann | Ricky Romero | Ricky Romero | Jeff Niemann | | 41 | 64 | -23 |
| 2012-04-18 | @ TOR | 12 | L 12-2 | 7-5 | 2 | 15,828 | David Price | Brandon Morrow | David Price | Brandon Morrow | | 53 | 66 | -13 |
| 2012-04-19 | @ TOR | 13 | W 9-4 | 8-5 | 1 | 18,976 | Jeremy Hellickson | Henderson Alvarez | Jeremy Hellickson | Henderson Alvarez | | 62 | 70 | -8 |
| 2012-04-20 | vs MIN | 14 | L 4-5 | 8-6 | 2 | 18,763 | Matt Moore | Liam Hendriks | Matt Maloney | Brandon Gomes | Matt Capps | 66 | 75 | -9 |
| 2012-04-21 | vs MIN | 15 | W 4-1 | 9-6 | 2 | 31,774 | James Shields | Carl Pavano | James Shields | Carl Pavano | Fernando Rodney | 70 | 76 | -6 |
| 2012-04-22 | vs MIN | 16 | W 6-2 | 10-6 | 2 | 26,507 | Jeff Niemann | Francisco Liriano | Jeff Niemann | Francisco Liriano | | 76 | 78 | -2 |
| 2012-04-24 | vs ANA | 17 | W 5-0 | 11-6 | 1 | 14,933 | David Price | Ervin Santana | David Price | Ervin Santana | | 81 | 78 | 3 |
| 2012-04-25 | vs ANA | 18 | W 3-2 | 12-6 | 1 | 14,638 | Jeremy Hellickson | C.J. Wilson | Jeremy Hellickson | C.J. Wilson | Fernando Rodney | 84 | 80 | 4 |
| 2012-04-26 | vs ANA | 19 | W 4-3 | 13-6 | 1 | 15,417 | Matt Moore | Jerome Williams | Brandon Gomes | Jordan Walden | | 88 | 83 | 5 |
| 2012-04-27 | @ TEX | 20 | W 8-4 | 14-6 | 1 | 47,496 | James Shields | Matt Harrison | James Shields | Matt Harrison | | 96 | 87 | 9 |
| 2012-04-28 | @ TEX | 21 | L 2-7 | 14-7 | 1 | 49,197 | Jeff Niemann | Colby Lewis | Colby Lewis | Jeff Niemann | | 98 | 94 | 4 |
| 2012-04-29 | @ TEX | 22 | W 5-2 | 15-7 | 1 | 43,475 | David Price | Derek Holland | David Price | Derek Holland | Fernando Rodney | 103 | 96 | 7 |
| 2012-04-30 | vs SEA | 23 | W 3-2 | 16-7 | 1 | 9,458 | Jeremy Hellickson | Felix Hernandez | J.P. Howell | Brandon League | | 106 | 98 | 8 |
| 2012-05-01 | vs SEA | 24 | W 3-1 | 17-7 | 1 | 9,972 | Matt Moore | Hector Noesi | Matt Moore | Hector Noesi | Fernando Rodney | 109 | 99 | 10 |
| 2012-05-02 | vs SEA | 25 | W 5-4 | 18-7 | 1 | 9,837 | James Shields | Blake Beavan | James Shields | Blake Beavan | Joel Peralta | 114 | 103 | 11 |
| 2012-05-03 | vs SEA | 26 | W 4-3 | 19-7 | 1 | 11,575 | Jeff Niemann | Kevin Millwood | Jeff Niemann | Kevin Millwood | Fernando Rodney | 118 | 106 | 12 |
| 2012-05-04 | vs OAK | 27 | W 7-2 | 20-7 | 1 | 18,799 | David Price | Tyson Ross | David Price | Tyson Ross | Joel Peralta | 125 | 108 | 17 |
| 2012-05-05 | vs OAK | 28 | L 3-4 | 20-8 | 1 | 23,890 | Jeremy Hellickson | Bartolo Colon | Brian Fuentes | Joel Peralta | Grant Balfour | 128 | 112 | 16 |
| 2012-05-06 | vs OAK | 29 | L 5-9 | 20-9 | 1 | 23,873 | Matt Moore | Tom Milone | Tom Milone | Matt Moore | | 133 | 121 | 12 |
| 2012-05-08 | @ NYA | 30 | L 3-5 | 20-10 | 2 | 37,086 | James Shields | Ivan Nova | Ivan Nova | James Shields | David Robertson | 136 | 126 | 10 |
| 2012-05-09 | @ NYA | 31 | W 4-1 | 21-10 | 1 | 38,024 | Jeff Niemann | David Phelps | Fernando Rodney | David Robertson | | 140 | 127 | 13 |
| 2012-05-10 | @ NYA | 32 | L 3-5 | 21-11 | 3 | 37,720 | David Price | CC Sabathia | CC Sabathia | David Price | Rafael Soriano | 143 | 132 | 11 |
| 2012-05-11 | @ BAL | 33 | L 3-4 | 21-12 | 2 | 26,669 | Jeremy Hellickson | Dana Eveland | Darren O'Day | Joel Peralta | Jim Johnson | 146 | 136 | 10 |
| 2012-05-12 | @ BAL | 34 | L 3-5 | 21-13 | 2 | 32,862 | Matt Moore | Brian Matusz | Brian Matusz | Matt Moore | Jim Johnson | 149 | 141 | 8 |
| 2012-05-13 | @ BAL | 35 | W 9-8 | 22-13 | 2 | 29,552 | James Shields | Jake Arrieta | James Shields | Jake Arrieta | Fernando Rodney | 158 | 149 | 9 |
| 2012-05-14 | @ TOR | 36 | W 7-1 | 23-13 | 2 | 15,289 | Jeff Niemann | Brandon Morrow | Cesar Ramos | Brandon Morrow | | 165 | 150 | 15 |
| 2012-05-15 | @ TOR | 37 | W 4-3 | 24-13 | 2 | 15,612 | David Price | Henderson Alvarez | David Price | Henderson Alvarez | Fernando Rodney | 169 | 153 | 16 |
| 2012-05-16 | vs BOS | 38 | W 2-1 | 25-13 | 2 | 20,843 | Jeremy Hellickson | Clay Buchholz | Jeremy Hellickson | Clay Buchholz | Fernando Rodney | 171 | 154 | 17 |
| 2012-05-17 | vs BOS | 39 | L 3-5 | 25-14 | 2 | 19,842 | Matt Moore | Felix Doubront | Felix Doubront | Matt Moore | Alfredo Aceves | 174 | 159 | 15 |
| 2012-05-18 | vs ATL | 40 | L 3-5 | 25-15 | 2 | 19,693 | James Shields | Tommy Hanson | Tommy Hanson | James Shields | Craig Kimbrel | 177 | 164 | 13 |
| 2012-05-19 | vs ATL | 41 | W 5-2 | 26-15 | 2 | 27,433 | Alex Cobb | Randall Delgado | Alex Cobb | Randall Delgado | Fernando Rodney | 182 | 166 | 16 |
| 2012-05-20 | vs ATL | 42 | L 0-2 | 26-16 | 2 | 24,759 | David Price | Tim Hudson | Tim Hudson | David Price | Craig Kimbrel | 182 | 168 | 14 |
| 2012-05-21 | vs TOR | 43 | L 2-6 | 26-17 | 2 | 10,844 | Jeremy Hellickson | Kyle Drabek | Kyle Drabek | Jeremy Hellickson | | 184 | 174 | 10 |
| 2012-05-22 | vs TOR | 44 | W 8-5 | 27-17 | 2 | 12,307 | Matt Moore | Drew Hutchison | Wade Davis | Drew Hutchison | Fernando Rodney | 192 | 179 | 13 |
| 2012-05-23 | vs TOR | 45 | W 5-4 | 28-17 | 2 | 11,471 | James Shields | Ricky Romero | Jake McGee | Darren Oliver | | 197 | 183 | 14 |
| 2012-05-25 | @ BOS | 46 | W 7-4 | 29-17 | 2 | 37,594 | Alex Cobb | Jon Lester | Alex Cobb | Jon Lester | Fernando Rodney | 204 | 187 | 17 |
| 2012-05-26 | @ BOS | 47 | L 2-3 | 29-18 | 2 | 38,099 | David Price | Josh Beckett | Rich Hill | Fernando Rodney | | 206 | 190 | 16 |
| 2012-05-27 | @ BOS | 48 | W 4-3 | 30-18 | 2 | 37,844 | Jeremy Hellickson | Clay Buchholz | Jake McGee | Alfredo Aceves | Fernando Rodney | 210 | 193 | 17 |
| 2012-05-28 | vs CHA | 49 | L 1-2 | 30-19 | 2 | 22,227 | Matt Moore | Chris Sale | Chris Sale | Matt Moore | Addison Reed | 211 | 195 | 16 |
| 2012-05-29 | vs CHA | 50 | L 2-7 | 30-20 | 2 | 13,735 | James Shields | Philip Humber | Philip Humber | James Shields | | 213 | 202 | 11 |
| 2012-05-30 | vs CHA | 51 | L 3-4 | 30-21 | 2 | 13,369 | Alex Cobb | Jose Quintana | Nate Jones | Alex Cobb | Addison Reed | 216 | 206 | 10 |
| 2012-06-01 | vs BAL | 52 | W 5-0 | 31-21 | 1 | 17,224 | David Price | Wei-Yin Chen | David Price | Wei-Yin Chen | Fernando Rodney | 221 | 206 | 15 |
| 2012-06-02 | vs BAL | 53 | L 1-2 | 31-22 | 2 | 21,693 | Jeremy Hellickson | Brian Matusz | Brian Matusz | Jeremy Hellickson | Jim Johnson | 222 | 208 | 14 |
| 2012-06-03 | vs BAL | 54 | W 8-4 | 32-22 | 1 | 21,693 | Matt Moore | Jake Arrieta | Matt Moore | Jake Arrieta | | 230 | 212 | 18 |
| 2012-06-05 | @ NYA | 55 | L 0-7 | 32-23 | 2 | 40,537 | James Shields | Andy Pettitte | Andy Pettitte | James Shields | | 230 | 219 | 11 |
| 2012-06-06 | @ NYA | 56 | L 1-4 | 32-24 | 2 | 38,370 | Alex Cobb | Ivan Nova | Ivan Nova | Alex Cobb | Rafael Soriano | 231 | 223 | 8 |
| 2012-06-07 | @ NYA | 57 | W 7-3 | 33-24 | 2 | 39,891 | David Price | CC Sabathia | David Price | CC Sabathia | | 238 | 226 | 12 |
| 2012-06-08 | @ MIA | 58 | W 5-1 | 34-24 | 1 | 29,628 | Jeremy Hellickson | Ricky Nolasco | Burke Badenhop | Ricky Nolasco | | 243 | 227 | 16 |
| 2012-06-09 | @ MIA | 59 | L 13-4 | 34-25 | 2 | 30,963 | Matt Moore | Carlos Zambrano | Matt Moore | Carlos Zambrano | | 256 | 231 | 25 |
| 2012-06-10 | @ MIA | 60 | W 4-2 | 35-25 | 2 | 31,111 | James Shields | Anibal Sanchez | James Shields | Anibal Sanchez | Fernando Rodney | 260 | 233 | 27 |
| 2012-06-12 | vs NYN | 61 | W 2-11 | 36-25 | 2 | 17,334 | Alex Cobb | Chris Young | Chris Young | Alex Cobb | | 262 | 244 | 18 |
| 2012-06-13 | vs NYN | 62 | L 1-9 | 36-26 | 2 | 18,496 | David Price | R.A. Dickey | R.A. Dickey | David Price | | 263 | 253 | 10 |
| 2012-06-14 | vs NYN | 63 | L 6-9 | 36-27 | 2 | 21,947 | Jeremy Hellickson | Johan Santana | Johan Santana | Jeremy Hellickson | Frank Francisco | 269 | 262 | 7 |
| 2012-06-15 | vs MIA | 64 | W 11-0 | 37-27 | 2 | 18,369 | Matt Moore | Carlos Zambrano | Matt Moore | Carlos Zambrano | | 280 | 262 | 18 |
| 2012-06-16 | vs MIA | 65 | L 3-4 | 37-28 | 2 | 22,332 | James Shields | Anibal Sanchez | Ryan Webb | Brandon Gomes | Heath Bell | 283 | 266 | 17 |
| 2012-06-17 | vs MIA | 66 | W 3-0 | 38-28 | 2 | 33,810 | Alex Cobb | Josh Johnson | Alex Cobb | Josh Johnson | Fernando Rodney | 286 | 266 | 20 |
| 2012-06-19 | @ WAS | 67 | W 5-4 | 39-28 | 1 | 27,835 | David Price | Chien-Ming Wang | David Price | Chien-Ming Wang | Fernando Rodney | 291 | 270 | 21 |
| 2012-06-20 | @ WAS | 68 | L 2-3 | 39-29 | 2 | 27,485 | Chris Archer | Stephen Strasburg | Stephen Strasburg | Chris Archer | Tyler Clippard | 293 | 273 | 20 |
| 2012-06-21 | @ WAS | 69 | L 2-5 | 39-30 | 2 | 29,551 | Matt Moore | Gio Gonzalez | Gio Gonzalez | Joel Peralta | Tyler Clippard | 295 | 278 | 17 |
| 2012-06-23 | @ PHI | 70 | L 6-7 | 39-31 | 3 | 44,878 | James Shields | Kyle Kendrick | Jonathan Papelbon | Jake McGee | | 301 | 285 | 16 |
| 2012-06-24 | @ PHI | 71 | W 3-2 | 40-31 | 4 | 44,785 | David Price | Cole Hamels | David Price | Antonio Bastardo | Fernando Rodney | 304 | 287 | 17 |
| 2012-06-24 | @ PHI | 72 | W 7-3 | 40-31 | 4 | 44,088 | Cesar Ramos | Cliff Lee | Brandon Gomes | Cliff Lee | | 311 | 290 | 21 |
| 2012-06-25 | @ KCA | 73 | L 0-8 | 41-32 | 3 | 20,200 | Alex Cobb | Luke Hochevar | Luke Hochevar | Alex Cobb | | 311 | 298 | 13 |
| 2012-06-26 | @ KCA | 74 | L 2-8 | 41-33 | 3 | 25,982 | Chris Archer | Bruce Chen | Bruce Chen | Chris Archer | | 313 | 306 | 7 |
| 2012-06-27 | @ KCA | 75 | L 4-5 | 41-34 | 3 | 19,228 | Matt Moore | Everett Teaford | Aaron Crow | Burke Badenhop | Jonathan Broxton | 317 | 311 | 6 |
| 2012-06-28 | vs DET | 76 | L 2-5 | 41-35 | 3 | 20,532 | James Shields | Max Scherzer | Max Scherzer | James Shields | Jose Valverde | 319 | 316 | 3 |
| 2012-06-29 | vs DET | 77 | W 4-2 | 42-35 | 3 | 19,557 | David Price | Justin Verlander | David Price | Justin Verlander | Fernando Rodney | 323 | 318 | 5 |
| 2012-06-30 | vs DET | 78 | L 2-6 | 42-36 | 3 | 29,443 | Jeremy Hellickson | Rick Porcello | Rick Porcello | Jeremy Hellickson | | 325 | 324 | 1 |
| 2012-07-01 | vs DET | 79 | L 3-5 | 42-37 | 3 | 21,874 | Alex Cobb | Drew Smyly | Drew Smyly | Alex Cobb | Jose Valverde | 328 | 329 | -1 |
| 2012-07-02 | vs NYA | 80 | W 4-3 | 43-37 | 3 | 21,742 | Matt Moore | Freddy Garcia | Matt Moore | David Robertson | Fernando Rodney | 332 | 332 | 0 |
| 2012-07-03 | vs NYA | 81 | W 7-4 | 44-37 | 3 | 26,453 | James Shields | Ivan Nova | James Shields | Ivan Nova | Fernando Rodney | 339 | 336 | 3 |
| 2012-07-04 | vs NYA | 82 | L 3-4 | 44-38 | 3 | 28,033 | David Price | David Phelps | Boone Logan | Kyle Farnsworth | Rafael Soriano | 342 | 340 | 2 |
| 2012-07-05 | @ CLE | 83 | L 1-3 | 44-39 | 3 | 26,577 | Jeremy Hellickson | Josh Tomlin | Josh Tomlin | Jeremy Hellickson | Chris Perez | 343 | 343 | 0 |
| 2012-07-06 | @ CLE | 84 | L 10-3 | 44-40 | 3 | 28,734 | Alex Cobb | Justin Masterson | Alex Cobb | Justin Masterson | | 353 | 346 | 7 |
| 2012-07-07 | @ CLE | 85 | L 3-7 | 44-41 | 4 | 20,658 | Matt Moore | Ubaldo Jimenez | Ubaldo Jimenez | Matt Moore | | 356 | 353 | 3 |
| 2012-07-08 | @ CLE | 86 | W 7-6 | 45-41 | 3 | 19,163 | James Shields | Zach McAllister | Joel Peralta | Chris Perez | Fernando Rodney | 363 | 359 | 4 |
| 2012-07-13 | vs BOS | 87 | L 1-3 | 45-42 | 3 | 29,089 | Jeremy Hellickson | Franklin Morales | Franklin Morales | Jeremy Hellickson | Alfredo Aceves | 364 | 362 | 2 |
| 2012-07-14 | vs BOS | 88 | W 5-3 | 46-42 | 3 | 27,311 | David Price | Clay Buchholz | David Price | Clay Buchholz | Fernando Rodney | 369 | 365 | 4 |
| 2012-07-15 | vs BOS | 89 | L 3-7 | 46-43 | 3 | 26,131 | James Shields | Josh Beckett | Josh Beckett | James Shields | | 372 | 372 | 0 |
| 2012-07-16 | vs CLE | 90 | L 2-3 | 46-44 | 3 | 14,337 | Alex Cobb | Zach McAllister | Zach McAllister | Alex Cobb | Chris Perez | 374 | 375 | -1 |
| 2012-07-17 | vs CLE | 91 | W 4-2 | 47-44 | 3 | 15,712 | Matt Moore | Josh Tomlin | Matt Moore | Josh Tomlin | Fernando Rodney | 378 | 377 | 1 |
| 2012-07-18 | vs CLE | 92 | W 6-10 | 48-44 | 3 | 15,143 | Jeremy Hellickson | Justin Masterson | Esmil Rogers | Kyle Farnsworth | | 384 | 387 | -3 |
| 2012-07-19 | vs CLE | 93 | W 6-0 | 49-44 | 3 | 27,856 | David Price | Ubaldo Jimenez | David Price | Ubaldo Jimenez | | 390 | 387 | 3 |
| 2012-07-20 | vs SEA | 94 | W 4-3 | 50-44 | 3 | 14,143 | James Shields | Hisashi Iwakuma | Jake McGee | Tom Wilhelmsen | | 394 | 390 | 4 |
| 2012-07-21 | vs SEA | 95 | L 1-2 | 50-45 | 3 | 18,800 | Alex Cobb | Jason Vargas | Jason Vargas | Alex Cobb | Tom Wilhelmsen | 395 | 392 | 3 |
| 2012-07-22 | vs SEA | 96 | L 1-2 | 50-46 | 3 | 20,908 | Matt Moore | Blake Beavan | Blake Beavan | Matt Moore | Tom Wilhelmsen | 396 | 394 | 2 |
| 2012-07-24 | @ BAL | 97 | W 3-1 | 51-46 | 3 | 17,592 | Jeremy Hellickson | Wei-Yin Chen | Jeremy Hellickson | Wei-Yin Chen | Fernando Rodney | 399 | 395 | 4 |
| 2012-07-25 | @ BAL | 98 | W 10-1 | 52-46 | 3 | 19,582 | David Price | Miguel Gonzalez | David Price | Miguel Gonzalez | | 409 | 396 | 13 |
| 2012-07-26 | @ BAL | 99 | L 2-6 | 52-47 | 3 | 21,301 | James Shields | Chris Tillman | Chris Tillman | James Shields | | 411 | 402 | 9 |
| 2012-07-27 | @ ANA | 100 | L 1-3 | 52-48 | 3 | 40,136 | Alex Cobb | Dan Haren | Dan Haren | Alex Cobb | Ernesto Frieri | 412 | 405 | 7 |
| 2012-07-28 | @ ANA | 101 | W 3-0 | 53-48 | 3 | 41,232 | Matt Moore | C.J. Wilson | Matt Moore | C.J. Wilson | Fernando Rodney | 415 | 405 | 10 |
| 2012-07-29 | @ ANA | 102 | W 2-0 | 54-48 | 3 | 35,477 | Jeremy Hellickson | Zack Greinke | Jeremy Hellickson | Zack Greinke | Fernando Rodney | 417 | 405 | 12 |
| 2012-07-30 | @ OAK | 103 | L 3-4 | 54-49 | 3 | 12,564 | David Price | A.J. Griffin | Jordan Norberto | Kyle Farnsworth | | 420 | 409 | 11 |
| 2012-07-31 | @ OAK | 104 | W 8-0 | 55-49 | 3 | 15,836 | James Shields | Tom Milone | James Shields | Tom Milone | | 428 | 409 | 19 |
| 2012-08-01 | @ OAK | 105 | W 4-1 | 56-49 | 3 | 18,161 | Alex Cobb | Jarrod Parker | Alex Cobb | Jarrod Parker | Fernando Rodney | 432 | 410 | 22 |
| 2012-08-03 | vs BAL | 106 | W 2-0 | 57-49 | 3 | 18,410 | Matt Moore | Tommy Hunter | Matt Moore | Tommy Hunter | Fernando Rodney | 434 | 410 | 24 |
| 2012-08-04 | vs BAL | 107 | L 0-4 | 57-50 | 3 | 20,612 | Jeremy Hellickson | Wei-Yin Chen | Wei-Yin Chen | Jeremy Hellickson | | 434 | 414 | 20 |
| 2012-08-05 | vs BAL | 108 | L 0-1 | 57-51 | 3 | 29,530 | David Price | Miguel Gonzalez | Luis Ayala | Joel Peralta | Jim Johnson | 434 | 415 | 19 |
| 2012-08-07 | vs TOR | 109 | W 4-1 | 58-51 | 3 | 13,823 | James Shields | J.A. Happ | James Shields | J.A. Happ | Fernando Rodney | 438 | 416 | 22 |
| 2012-08-08 | vs TOR | 110 | W 3-2 | 59-51 | 3 | 13,441 | Alex Cobb | Carlos Villanueva | Alex Cobb | Carlos Villanueva | Fernando Rodney | 441 | 418 | 23 |
| 2012-08-09 | vs TOR | 111 | W 7-1 | 60-51 | 3 | 23,462 | Matt Moore | Henderson Alvarez | Matt Moore | Henderson Alvarez | | 448 | 419 | 29 |
| 2012-08-10 | @ MIN | 112 | L 12-6 | 60-52 | 3 | 38,108 | Jeremy Hellickson | Cole De Vries | Jeremy Hellickson | Cole De Vries | | 460 | 425 | 35 |
| 2012-08-11 | @ MIN | 113 | W 4-2 | 61-52 | 3 | 39,512 | David Price | Nick Blackburn | David Price | Nick Blackburn | Fernando Rodney | 464 | 427 | 37 |
| 2012-08-12 | @ MIN | 114 | W 7-3 | 62-52 | 3 | 35,327 | James Shields | Scott Diamond | Kyle Farnsworth | Alex Burnett | Fernando Rodney | 471 | 430 | 41 |
| 2012-08-13 | @ SEA | 115 | W 4-1 | 63-52 | 3 | 16,205 | Alex Cobb | Blake Beavan | Alex Cobb | Blake Beavan | Fernando Rodney | 475 | 431 | 44 |
| 2012-08-14 | @ SEA | 116 | L 2-3 | 63-53 | 3 | 17,065 | Matt Moore | Kevin Millwood | Stephen Pryor | Fernando Rodney | | 477 | 434 | 43 |
| 2012-08-15 | @ SEA | 117 | L 0-1 | 63-54 | 3 | 21,889 | Jeremy Hellickson | Felix Hernandez | Felix Hernandez | Jeremy Hellickson | | 477 | 435 | 42 |
| 2012-08-16 | @ ANA | 118 | W 7-0 | 64-54 | 3 | 38,591 | David Price | Dan Haren | David Price | Dan Haren | | 484 | 435 | 49 |
| 2012-08-17 | @ ANA | 119 | L 12-3 | 64-55 | 3 | 37,298 | James Shields | Jered Weaver | James Shields | Jered Weaver | | 496 | 438 | 58 |
| 2012-08-18 | @ ANA | 120 | L 10-8 | 64-56 | 3 | 41,086 | Alex Cobb | C.J. Wilson | Jake McGee | Kevin Jepsen | Fernando Rodney | 506 | 446 | 60 |
| 2012-08-19 | @ ANA | 121 | W 8-3 | 65-56 | 3 | 36,789 | Matt Moore | Zack Greinke | Matt Moore | Zack Greinke | | 514 | 449 | 65 |
| 2012-08-20 | vs KCA | 122 | W 5-1 | 66-56 | 3 | 9,913 | Jeremy Hellickson | Will Smith | Jeremy Hellickson | Will Smith | | 519 | 450 | 69 |
| 2012-08-21 | vs KCA | 123 | L 0-1 | 66-57 | 3 | 10,877 | David Price | Luke Hochevar | Kelvin Herrera | Joel Peralta | Greg Holland | 519 | 451 | 68 |
| 2012-08-22 | vs KCA | 124 | W 5-3 | 67-57 | 3 | 11,892 | James Shields | Luis Mendoza | James Shields | Luis Mendoza | Fernando Rodney | 524 | 454 | 70 |
| 2012-08-23 | vs OAK | 125 | W 5-0 | 68-57 | 3 | 11,613 | Alex Cobb | Tyson Ross | Alex Cobb | Tyson Ross | | 529 | 454 | 75 |
| 2012-08-24 | vs OAK | 126 | L 4-5 | 68-58 | 3 | 18,913 | Matt Moore | Jarrod Parker | Ryan Cook | Joel Peralta | Grant Balfour | 533 | 459 | 74 |
| 2012-08-25 | vs OAK | 127 | L 2-4 | 68-59 | 3 | 18,187 | Jeremy Hellickson | Brandon McCarthy | Brandon McCarthy | Jeremy Hellickson | Grant Balfour | 535 | 463 | 72 |
| 2012-08-27 | @ TEX | 128 | L 5-6 | 68-60 | 3 | 29,453 | David Price | Derek Holland | Derek Holland | David Price | Joe Nathan | 540 | 469 | 71 |
| 2012-08-28 | @ TEX | 129 | L 0-1 | 68-61 | 3 | 30,700 | James Shields | Yu Darvish | Yu Darvish | James Shields | Joe Nathan | 540 | 470 | 70 |
| 2012-08-29 | @ TEX | 130 | W 8-4 | 69-61 | 3 | 36,176 | Alex Cobb | Matt Harrison | Jake McGee | Matt Harrison | | 548 | 474 | 74 |
| 2012-08-30 | @ TOR | 131 | L 0-2 | 69-62 | 3 | 22,711 | Matt Moore | Carlos Villanueva | Carlos Villanueva | Matt Moore | Casey Janssen | 548 | 476 | 72 |
| 2012-08-31 | @ TOR | 132 | L 1-2 | 69-63 | 3 | 20,158 | Jeremy Hellickson | Brandon Morrow | Brandon Morrow | Jeremy Hellickson | Casey Janssen | 549 | 478 | 71 |
| 2012-09-01 | @ TOR | 133 | W 5-4 | 70-63 | 3 | 20,478 | Jeff Niemann | Henderson Alvarez | Wade Davis | Henderson Alvarez | Fernando Rodney | 554 | 482 | 72 |
| 2012-09-02 | @ TOR | 134 | W 9-4 | 71-63 | 3 | 18,568 | David Price | Ricky Romero | David Price | Ricky Romero | | 563 | 486 | 77 |
| 2012-09-03 | vs NYA | 135 | W 4-3 | 72-63 | 3 | 28,585 | James Shields | CC Sabathia | James Shields | David Robertson | Fernando Rodney | 567 | 489 | 78 |
| 2012-09-04 | vs NYA | 136 | W 5-2 | 73-63 | 3 | 17,652 | Alex Cobb | Freddy Garcia | Alex Cobb | Freddy Garcia | Fernando Rodney | 572 | 491 | 81 |
| 2012-09-05 | vs NYA | 137 | L 4-6 | 73-64 | 3 | 16,711 | Matt Moore | Hiroki Kuroda | Hiroki Kuroda | Matt Moore | Rafael Soriano | 576 | 497 | 79 |
| 2012-09-07 | vs TEX | 138 | W 3-1 | 74-64 | 3 | 19,545 | Jeremy Hellickson | Derek Holland | Wade Davis | Mark Lowe | | 579 | 498 | 81 |
| 2012-09-08 | vs TEX | 139 | L 2-4 | 74-65 | 3 | 18,702 | Chris Archer | Yu Darvish | Mike Adams | Kyle Farnsworth | Joe Nathan | 581 | 502 | 79 |
| 2012-09-09 | vs TEX | 140 | W 6-0 | 75-65 | 3 | 20,522 | James Shields | Roy Oswalt | James Shields | Roy Oswalt | | 587 | 502 | 85 |
| 2012-09-11 | @ BAL | 141 | L 2-9 | 75-66 | 3 | 23,828 | Matt Moore | Jason Hammel | Steve Johnson | Matt Moore | | 589 | 511 | 78 |
| 2012-09-12 | @ BAL | 142 | L 2-3 | 75-67 | 3 | 26,076 | Alex Cobb | Miguel Gonzalez | Jim Johnson | Kyle Farnsworth | | 591 | 514 | 77 |
| 2012-09-13 | @ BAL | 143 | L 2-3 | 75-68 | 3 | 25,130 | Jeremy Hellickson | Wei-Yin Chen | Randy Wolf | Chris Archer | | 593 | 517 | 76 |
| 2012-09-14 | @ NYA | 144 | W 6-4 | 76-68 | 3 | 45,200 | David Price | CC Sabathia | David Price | CC Sabathia | Fernando Rodney | 599 | 521 | 78 |
| 2012-09-15 | @ NYA | 145 | L 3-5 | 76-69 | 3 | 46,856 | James Shields | Ivan Nova | Ivan Nova | James Shields | Rafael Soriano | 602 | 526 | 76 |
| 2012-09-16 | @ NYA | 146 | L 4-6 | 76-70 | 3 | 43,489 | Matt Moore | Hiroki Kuroda | Hiroki Kuroda | Matt Moore | Rafael Soriano | 606 | 532 | 74 |
| 2012-09-17 | vs BOS | 147 | L 2-5 | 76-71 | 3 | 11,722 | Alex Cobb | Aaron Cook | Aaron Cook | Alex Cobb | | 608 | 537 | 71 |
| 2012-09-18 | vs BOS | 148 | L 5-7 | 76-72 | 3 | 11,502 | Jeremy Hellickson | Felix Doubront | Felix Doubront | Kyle Farnsworth | Andrew Bailey | 613 | 544 | 69 |
| 2012-09-19 | vs BOS | 149 | L 13-3 | 76-73 | 4 | 12,708 | Chris Archer | Daisuke Matsuzaka | Chris Archer | Daisuke Matsuzaka | | 626 | 547 | 79 |
| 2012-09-20 | vs BOS | 150 | W 7-4 | 77-73 | 3 | 12,963 | David Price | Clay Buchholz | Burke Badenhop | Andrew Bailey | | 633 | 551 | 82 |
| 2012-09-21 | vs TOR | 151 | W 12-1 | 78-73 | 3 | 14,187 | James Shields | Carlos Villanueva | James Shields | Carlos Villanueva | | 645 | 552 | 93 |
| 2012-09-22 | vs TOR | 152 | L 11-5 | 78-74 | 3 | 15,699 | Matt Moore | Brandon Morrow | Burke Badenhop | Brandon Morrow | | 656 | 557 | 99 |
| 2012-09-23 | vs TOR | 153 | W 3-0 | 79-74 | 3 | 18,985 | Jeremy Hellickson | Chad Jenkins | Jeremy Hellickson | Chad Jenkins | Fernando Rodney | 659 | 557 | 102 |
| 2012-09-25 | @ BOS | 154 | W 5-2 | 80-74 | 3 | 37,045 | David Price | Clay Buchholz | David Price | Clay Buchholz | | 664 | 559 | 105 |
| 2012-09-26 | @ BOS | 155 | W 4-2 | 81-74 | 3 | 37,247 | Alex Cobb | Jon Lester | Alex Cobb | Jon Lester | Fernando Rodney | 668 | 561 | 107 |
| 2012-09-27 | @ CHA | 156 | W 3-2 | 82-74 | 3 | 18,630 | James Shields | Jake Peavy | Joel Peralta | Brett Myers | Fernando Rodney | 671 | 563 | 108 |
| 2012-09-28 | @ CHA | 157 | L 1-3 | 82-75 | 3 | 25,264 | Jeremy Hellickson | Gavin Floyd | Gavin Floyd | Jeremy Hellickson | Addison Reed | 672 | 566 | 106 |
| 2012-09-29 | @ CHA | 158 | L 10-4 | 82-76 | 3 | 26,559 | Matt Moore | Chris Sale | Matt Moore | Chris Sale | | 682 | 570 | 112 |
| 2012-09-30 | @ CHA | 159 | W 6-2 | 83-76 | 3 | 26,831 | David Price | Jose Quintana | David Price | Jose Quintana | | 688 | 572 | 116 |
| 2012-10-01 | vs BAL | 160 | W 5-3 | 84-76 | 3 | 13,666 | Alex Cobb | Wei-Yin Chen | Alex Cobb | Wei-Yin Chen | Fernando Rodney | 693 | 575 | 118 |
| 2012-10-02 | vs BAL | 161 | L 0-1 | 84-77 | 3 | 13,460 | James Shields | Miguel Gonzalez | Miguel Gonzalez | James Shields | Jim Johnson | 693 | 576 | 117 |
| 2012-10-03 | vs BAL | 162 | W 4-1 | 85-77 | 3 | 17,909 | Jeremy Hellickson | Chris Tillman | Jeremy Hellickson | Chris Tillman | Fernando Rodney | 697 | 577 | 120 |