| 2012-04-05 | @ CLE | 1 | W 7-4 | 1-0 | 1 | 43,190 | Ricky Romero | Justin Masterson | Luis Perez | Luis Valdez | | 7 | 4 | 3 |
| 2012-04-07 | @ CLE | 2 | W 7-4 | 2-0 | 3 | 18,842 | Brandon Morrow | Ubaldo Jimenez | Casey Janssen | Tony Sipp | | 14 | 8 | 6 |
| 2012-04-08 | @ CLE | 3 | L 3-4 | 2-1 | 3 | 10,518 | Joel Carreno | Derek Lowe | Derek Lowe | Joel Carreno | Chris Perez | 17 | 12 | 5 |
| 2012-04-09 | vs BOS | 4 | L 2-4 | 2-2 | 3 | 48,473 | Henderson Alvarez | Felix Doubront | Scott Atchison | Sergio Santos | Alfredo Aceves | 19 | 16 | 3 |
| 2012-04-10 | vs BOS | 5 | W 7-3 | 3-2 | 3 | 26,351 | Kyle Drabek | Daniel Bard | Kyle Drabek | Daniel Bard | | 26 | 19 | 7 |
| 2012-04-11 | vs BOS | 6 | W 3-1 | 4-2 | 2 | 25,285 | Ricky Romero | Jon Lester | Ricky Romero | Jon Lester | Sergio Santos | 29 | 20 | 9 |
| 2012-04-13 | vs BAL | 7 | L 5-7 | 4-3 | 4 | 21,988 | Brandon Morrow | Tommy Hunter | Darren O'Day | Darren Oliver | Jim Johnson | 34 | 27 | 7 |
| 2012-04-14 | vs BAL | 8 | L 4-6 | 4-4 | 4 | 28,355 | Henderson Alvarez | Jason Hammel | Luis Ayala | Francisco Cordero | Jim Johnson | 38 | 33 | 5 |
| 2012-04-15 | vs BAL | 9 | W 9-2 | 5-4 | 3 | 20,252 | Kyle Drabek | Brian Matusz | Kyle Drabek | Brian Matusz | | 47 | 35 | 12 |
| 2012-04-17 | vs TBA | 10 | W 7-3 | 6-4 | 2 | 15,331 | Ricky Romero | Jeff Niemann | Ricky Romero | Jeff Niemann | | 54 | 38 | 16 |
| 2012-04-18 | vs TBA | 11 | W 2-12 | 7-4 | 1 | 15,828 | Brandon Morrow | David Price | David Price | Brandon Morrow | | 56 | 50 | 6 |
| 2012-04-19 | vs TBA | 12 | L 4-9 | 7-5 | 2 | 18,976 | Henderson Alvarez | Jeremy Hellickson | Jeremy Hellickson | Henderson Alvarez | | 60 | 59 | 1 |
| 2012-04-20 | @ KCA | 13 | W 4-3 | 8-5 | 1 | 23,065 | Kyle Drabek | Luke Hochevar | Luis Perez | Greg Holland | Sergio Santos | 64 | 62 | 2 |
| 2012-04-21 | @ KCA | 14 | W 9-5 | 9-5 | 1 | 27,804 | Drew Hutchison | Luis Mendoza | Drew Hutchison | Everett Teaford | | 73 | 67 | 6 |
| 2012-04-22 | @ KCA | 15 | W 5-3 | 10-5 | 1 | 26,891 | Ricky Romero | Danny Duffy | Ricky Romero | Danny Duffy | Francisco Cordero | 78 | 70 | 8 |
| 2012-04-23 | @ KCA | 16 | W 4-1 | 11-5 | 1 | 13,267 | Brandon Morrow | Bruce Chen | Brandon Morrow | Bruce Chen | Francisco Cordero | 82 | 71 | 11 |
| 2012-04-24 | @ BAL | 17 | L 1-2 | 11-6 | 2 | 11,058 | Henderson Alvarez | Tommy Hunter | Tommy Hunter | Henderson Alvarez | Pedro Strop | 83 | 73 | 10 |
| 2012-04-25 | @ BAL | 18 | L 0-3 | 11-7 | 2 | 10,415 | Kyle Drabek | Jason Hammel | Jason Hammel | Kyle Drabek | Pedro Strop | 83 | 76 | 7 |
| 2012-04-26 | @ BAL | 19 | L 2-5 | 11-8 | 3 | 13,725 | Drew Hutchison | Brian Matusz | Darren O'Day | Casey Janssen | Luis Ayala | 85 | 81 | 4 |
| 2012-04-27 | vs SEA | 20 | L 5-9 | 11-9 | 3 | 24,303 | Ricky Romero | Blake Beavan | Charlie Furbush | Luis Perez | | 90 | 90 | 0 |
| 2012-04-28 | vs SEA | 21 | W 7-0 | 12-9 | 3 | 30,765 | Brandon Morrow | Kevin Millwood | Brandon Morrow | Kevin Millwood | | 97 | 90 | 7 |
| 2012-04-29 | vs SEA | 22 | W 7-2 | 13-9 | 3 | 22,320 | Henderson Alvarez | Jason Vargas | Henderson Alvarez | Jason Vargas | | 104 | 92 | 12 |
| 2012-04-30 | vs TEX | 23 | L 1-4 | 13-10 | 3 | 21,945 | Kyle Drabek | Yu Darvish | Yu Darvish | Kyle Drabek | Joe Nathan | 105 | 96 | 9 |
| 2012-05-01 | vs TEX | 24 | W 8-7 | 14-10 | 3 | 18,774 | Drew Hutchison | Neftali Feliz | Francisco Cordero | Mike Adams | | 113 | 103 | 10 |
| 2012-05-02 | vs TEX | 25 | L 11-5 | 14-11 | 3 | 25,123 | Ricky Romero | Matt Harrison | Ricky Romero | Matt Harrison | | 124 | 108 | 16 |
| 2012-05-03 | @ ANA | 26 | W 5-0 | 15-11 | 3 | 28,359 | Brandon Morrow | Dan Haren | Brandon Morrow | Dan Haren | | 129 | 108 | 21 |
| 2012-05-04 | @ ANA | 27 | W 4-0 | 16-11 | 3 | 33,160 | Henderson Alvarez | Ervin Santana | Henderson Alvarez | Ervin Santana | | 133 | 108 | 25 |
| 2012-05-05 | @ ANA | 28 | L 2-6 | 16-12 | 3 | 39,018 | Kyle Drabek | C.J. Wilson | C.J. Wilson | Kyle Drabek | | 135 | 114 | 21 |
| 2012-05-06 | @ ANA | 29 | L 3-4 | 16-13 | 3 | 37,548 | Drew Hutchison | Jerome Williams | Jerome Williams | Drew Hutchison | LaTroy Hawkins | 138 | 118 | 20 |
| 2012-05-08 | @ OAK | 30 | L 3-7 | 16-14 | 3 | 10,784 | Ricky Romero | Jarrod Parker | Grant Balfour | Francisco Cordero | | 141 | 125 | 16 |
| 2012-05-09 | @ OAK | 31 | W 5-2 | 17-14 | 3 | 14,815 | Brandon Morrow | Tyson Ross | Brandon Morrow | Tyson Ross | Casey Janssen | 146 | 127 | 19 |
| 2012-05-10 | @ MIN | 32 | W 6-2 | 18-14 | 4 | 31,438 | Henderson Alvarez | Jason Marquis | Henderson Alvarez | Jason Marquis | | 152 | 129 | 23 |
| 2012-05-11 | @ MIN | 33 | L 6-7 | 18-15 | 3 | 33,387 | Kyle Drabek | Nick Blackburn | Nick Blackburn | Kyle Drabek | Matt Capps | 158 | 136 | 22 |
| 2012-05-12 | @ MIN | 34 | W 2-1 | 19-15 | 3 | 38,820 | Drew Hutchison | P.J. Walters | Drew Hutchison | P.J. Walters | Casey Janssen | 160 | 137 | 23 |
| 2012-05-13 | @ MIN | 35 | L 3-4 | 19-16 | 3 | 36,889 | Ricky Romero | Scott Diamond | Scott Diamond | Ricky Romero | Matt Capps | 163 | 141 | 22 |
| 2012-05-14 | vs TBA | 36 | L 1-7 | 19-17 | 3 | 15,289 | Brandon Morrow | Jeff Niemann | Cesar Ramos | Brandon Morrow | | 164 | 148 | 16 |
| 2012-05-15 | vs TBA | 37 | L 3-4 | 19-18 | 3 | 15,612 | Henderson Alvarez | David Price | David Price | Henderson Alvarez | Fernando Rodney | 167 | 152 | 15 |
| 2012-05-16 | vs NYA | 38 | W 8-1 | 20-18 | 3 | 28,915 | Kyle Drabek | Hiroki Kuroda | Kyle Drabek | Hiroki Kuroda | | 175 | 153 | 22 |
| 2012-05-17 | vs NYA | 39 | W 4-1 | 21-18 | 3 | 31,266 | Drew Hutchison | Phil Hughes | Drew Hutchison | Phil Hughes | Casey Janssen | 179 | 154 | 25 |
| 2012-05-18 | vs NYN | 40 | L 14-5 | 21-19 | 3 | 26,712 | Ricky Romero | Jonathon Niese | Ricky Romero | Jonathon Niese | | 193 | 159 | 34 |
| 2012-05-19 | vs NYN | 41 | W 2-0 | 22-19 | 3 | 34,962 | Brandon Morrow | Miguel Batista | Brandon Morrow | Jeremy Hefner | | 195 | 159 | 36 |
| 2012-05-20 | vs NYN | 42 | L 5-6 | 22-20 | 3 | 41,867 | Henderson Alvarez | Dillon Gee | Dillon Gee | Henderson Alvarez | Frank Francisco | 200 | 165 | 35 |
| 2012-05-21 | @ TBA | 43 | W 6-2 | 23-20 | 3 | 10,844 | Kyle Drabek | Jeremy Hellickson | Kyle Drabek | Jeremy Hellickson | | 206 | 167 | 39 |
| 2012-05-22 | @ TBA | 44 | L 5-8 | 23-21 | 3 | 12,307 | Drew Hutchison | Matt Moore | Wade Davis | Drew Hutchison | Fernando Rodney | 211 | 175 | 36 |
| 2012-05-23 | @ TBA | 45 | L 4-5 | 23-22 | 3 | 11,471 | Ricky Romero | James Shields | Jake McGee | Darren Oliver | | 215 | 180 | 35 |
| 2012-05-25 | @ TEX | 46 | W 3-14 | 24-22 | 3 | 46,789 | Brandon Morrow | Derek Holland | Derek Holland | Brandon Morrow | | 218 | 194 | 24 |
| 2012-05-26 | @ TEX | 47 | L 7-8 | 24-23 | 3 | 47,430 | Henderson Alvarez | Colby Lewis | Yoshinori Tateyama | Jason Frasor | | 225 | 202 | 23 |
| 2012-05-27 | @ TEX | 48 | W 6-12 | 25-23 | 3 | 46,637 | Kyle Drabek | Yu Darvish | Yu Darvish | Kyle Drabek | | 231 | 214 | 17 |
| 2012-05-28 | vs BAL | 49 | W 6-2 | 26-23 | 3 | 16,575 | Drew Hutchison | Tommy Hunter | Drew Hutchison | Tommy Hunter | Casey Janssen | 237 | 216 | 21 |
| 2012-05-29 | vs BAL | 50 | W 8-6 | 27-23 | 3 | 17,352 | Ricky Romero | Jake Arrieta | Ricky Romero | Jake Arrieta | | 245 | 222 | 23 |
| 2012-05-30 | vs BAL | 51 | W 4-1 | 28-23 | 3 | 17,754 | Brandon Morrow | Jason Hammel | Brandon Morrow | Jason Hammel | Casey Janssen | 249 | 223 | 26 |
| 2012-06-01 | vs BOS | 52 | L 2-7 | 28-24 | 3 | 29,678 | Henderson Alvarez | Clay Buchholz | Clay Buchholz | Henderson Alvarez | | 251 | 230 | 21 |
| 2012-06-02 | vs BOS | 53 | L 4-7 | 28-25 | 3 | 43,390 | Kyle Drabek | Felix Doubront | Felix Doubront | Kyle Drabek | Alfredo Aceves | 255 | 237 | 18 |
| 2012-06-03 | vs BOS | 54 | W 5-1 | 29-25 | 3 | 41,925 | Drew Hutchison | Daniel Bard | Drew Hutchison | Daniel Bard | | 260 | 238 | 22 |
| 2012-06-05 | @ CHA | 55 | W 9-5 | 30-25 | 3 | 23,107 | Ricky Romero | Philip Humber | Ricky Romero | Philip Humber | | 269 | 243 | 26 |
| 2012-06-06 | @ CHA | 56 | W 4-0 | 31-25 | 3 | 25,672 | Brandon Morrow | Jose Quintana | Brandon Morrow | Jose Quintana | | 273 | 243 | 30 |
| 2012-06-07 | @ CHA | 57 | L 3-4 | 31-26 | 3 | 25,743 | Henderson Alvarez | Jake Peavy | Addison Reed | Francisco Cordero | | 276 | 247 | 29 |
| 2012-06-08 | @ ATL | 58 | L 3-4 | 31-27 | 3 | 42,488 | Kyle Drabek | Brandon Beachy | Cristhian Martinez | Francisco Cordero | | 279 | 251 | 28 |
| 2012-06-09 | @ ATL | 59 | L 2-5 | 31-28 | 3 | 32,819 | Drew Hutchison | Tommy Hanson | Tommy Hanson | Drew Hutchison | Craig Kimbrel | 281 | 256 | 25 |
| 2012-06-10 | @ ATL | 60 | L 12-4 | 31-29 | 4 | 20,222 | Ricky Romero | Julio Teheran | Carlos Villanueva | Livan Hernandez | | 293 | 260 | 33 |
| 2012-06-11 | vs WAS | 61 | L 3-6 | 31-30 | 4 | 18,513 | Brandon Morrow | Edwin Jackson | Edwin Jackson | Brandon Morrow | | 296 | 266 | 30 |
| 2012-06-12 | vs WAS | 62 | L 2-4 | 31-31 | 4 | 22,538 | Henderson Alvarez | Chien-Ming Wang | Chien-Ming Wang | Henderson Alvarez | Tyler Clippard | 298 | 270 | 28 |
| 2012-06-13 | vs WAS | 63 | L 2-6 | 31-32 | 4 | 41,677 | Kyle Drabek | Stephen Strasburg | Stephen Strasburg | Kyle Drabek | | 300 | 276 | 24 |
| 2012-06-15 | vs PHI | 64 | W 3-0 | 32-32 | 4 | 28,266 | Drew Hutchison | Vance Worley | Carlos Villanueva | Vance Worley | Casey Janssen | 303 | 276 | 27 |
| 2012-06-16 | vs PHI | 65 | W 6-5 | 33-32 | 4 | 42,070 | Ricky Romero | Cliff Lee | Francisco Cordero | Joe Savery | | 309 | 281 | 28 |
| 2012-06-17 | vs PHI | 66 | W 6-2 | 34-32 | 4 | 45,060 | Brett Cecil | Kyle Kendrick | Brett Cecil | Kyle Kendrick | | 315 | 283 | 32 |
| 2012-06-18 | @ MIL | 67 | L 6-7 | 34-33 | 4 | 32,223 | Henderson Alvarez | Randy Wolf | Kameron Loe | Robert Coello | John Axford | 321 | 290 | 31 |
| 2012-06-19 | @ MIL | 68 | L 10-9 | 34-34 | 4 | 36,334 | Jesse Chavez | Tyler Thornburg | Darren Oliver | John Axford | Casey Janssen | 331 | 299 | 32 |
| 2012-06-20 | @ MIL | 69 | L 3-8 | 34-35 | 4 | 33,077 | Joel Carreno | Yovani Gallardo | Yovani Gallardo | Joel Carreno | | 334 | 307 | 27 |
| 2012-06-22 | @ MIA | 70 | L 12-5 | 34-36 | 4 | 22,387 | Ricky Romero | Anibal Sanchez | Ricky Romero | Anibal Sanchez | | 346 | 312 | 34 |
| 2012-06-23 | @ MIA | 71 | W 7-1 | 35-36 | 4 | 24,448 | Brett Cecil | Josh Johnson | Darren Oliver | Steve Cishek | | 353 | 313 | 40 |
| 2012-06-24 | @ MIA | 72 | L 0-9 | 35-37 | 5 | 27,888 | Jesse Chavez | Mark Buehrle | Mark Buehrle | Jesse Chavez | | 353 | 322 | 31 |
| 2012-06-25 | @ BOS | 73 | W 9-6 | 36-37 | 4 | 37,208 | Henderson Alvarez | Felix Doubront | Henderson Alvarez | Felix Doubront | Casey Janssen | 362 | 328 | 34 |
| 2012-06-26 | @ BOS | 74 | L 1-5 | 36-38 | 4 | 37,755 | Aaron Laffey | Daisuke Matsuzaka | Andrew Miller | Luis Perez | | 363 | 333 | 30 |
| 2012-06-27 | @ BOS | 75 | W 4-10 | 37-38 | 4 | 37,744 | Ricky Romero | Jon Lester | Jon Lester | Ricky Romero | | 367 | 343 | 24 |
| 2012-06-28 | vs ANA | 76 | L 7-9 | 37-39 | 4 | 24,668 | Brett Cecil | Dan Haren | Dan Haren | Brett Cecil | Ernesto Frieri | 374 | 352 | 22 |
| 2012-06-29 | vs ANA | 77 | W 7-5 | 38-39 | 4 | 24,538 | Carlos Villanueva | Ervin Santana | Francisco Cordero | Jordan Walden | Casey Janssen | 381 | 357 | 24 |
| 2012-06-30 | vs ANA | 78 | L 11-2 | 38-40 | 4 | 29,287 | Henderson Alvarez | Garrett Richards | Henderson Alvarez | Garrett Richards | | 392 | 359 | 33 |
| 2012-07-01 | vs ANA | 79 | W 6-10 | 39-40 | 4 | 34,853 | Aaron Laffey | C.J. Wilson | Jason Isringhausen | Francisco Cordero | | 398 | 369 | 29 |
| 2012-07-02 | vs KCA | 80 | W 3-11 | 40-40 | 4 | 17,127 | Ricky Romero | Everett Teaford | Everett Teaford | Ricky Romero | | 401 | 380 | 21 |
| 2012-07-03 | vs KCA | 81 | W 6-3 | 41-40 | 4 | 15,516 | Brett Cecil | Vin Mazzaro | Brett Cecil | Vin Mazzaro | Casey Janssen | 407 | 383 | 24 |
| 2012-07-04 | vs KCA | 82 | W 4-1 | 42-40 | 4 | 17,831 | Carlos Villanueva | Luis Mendoza | Carlos Villanueva | Luis Mendoza | Casey Janssen | 411 | 384 | 27 |
| 2012-07-05 | vs KCA | 83 | L 6-9 | 42-41 | 4 | 20,598 | Henderson Alvarez | Luke Hochevar | Luke Hochevar | Henderson Alvarez | Jonathan Broxton | 417 | 393 | 24 |
| 2012-07-06 | @ CHA | 84 | L 2-4 | 42-42 | 4 | 27,129 | Aaron Laffey | Jake Peavy | Jake Peavy | Aaron Laffey | Addison Reed | 419 | 397 | 22 |
| 2012-07-07 | @ CHA | 85 | L 0-2 | 42-43 | 5 | 25,399 | Ricky Romero | Gavin Floyd | Gavin Floyd | Ricky Romero | Matt Thornton | 419 | 399 | 20 |
| 2012-07-08 | @ CHA | 86 | L 11-9 | 42-44 | 4 | 27,190 | Brett Cecil | Dylan Axelrod | Jason Frasor | Dylan Axelrod | Casey Janssen | 430 | 408 | 22 |
| 2012-07-13 | vs CLE | 87 | L 0-1 | 42-45 | 4 | 32,308 | Ricky Romero | Justin Masterson | Justin Masterson | Ricky Romero | Chris Perez | 430 | 409 | 21 |
| 2012-07-14 | vs CLE | 88 | L 11-9 | 42-46 | 4 | 32,517 | Aaron Laffey | Ubaldo Jimenez | Aaron Laffey | Ubaldo Jimenez | Casey Janssen | 441 | 418 | 23 |
| 2012-07-15 | vs CLE | 89 | W 3-0 | 43-46 | 4 | 26,407 | Carlos Villanueva | Derek Lowe | Carlos Villanueva | Derek Lowe | Darren Oliver | 444 | 418 | 26 |
| 2012-07-16 | @ NYA | 90 | L 3-6 | 43-47 | 4 | 42,819 | Henderson Alvarez | Phil Hughes | David Robertson | Aaron Loup | Rafael Soriano | 447 | 424 | 23 |
| 2012-07-17 | @ NYA | 91 | L 1-6 | 43-48 | 4 | 44,975 | Brett Cecil | CC Sabathia | CC Sabathia | Brett Cecil | Rafael Soriano | 448 | 430 | 18 |
| 2012-07-18 | @ NYA | 92 | L 0-6 | 43-49 | 4 | 45,986 | Ricky Romero | Hiroki Kuroda | Hiroki Kuroda | Ricky Romero | | 448 | 436 | 12 |
| 2012-07-20 | @ BOS | 93 | W 6-1 | 44-49 | 4 | 38,093 | Aaron Laffey | Josh Beckett | Aaron Laffey | Josh Beckett | | 454 | 437 | 17 |
| 2012-07-21 | @ BOS | 94 | W 7-3 | 45-49 | 4 | 38,170 | Carlos Villanueva | Aaron Cook | Carlos Villanueva | Aaron Cook | | 461 | 440 | 21 |
| 2012-07-22 | @ BOS | 95 | L 15-7 | 45-50 | 4 | 37,737 | Henderson Alvarez | Jon Lester | Henderson Alvarez | Jon Lester | | 476 | 447 | 29 |
| 2012-07-24 | vs OAK | 96 | L 2-7 | 45-51 | 4 | 25,686 | Brett Cecil | Travis Blackley | Travis Blackley | Brett Cecil | | 478 | 454 | 24 |
| 2012-07-25 | vs OAK | 97 | L 0-16 | 45-52 | 4 | 23,948 | Ricky Romero | A.J. Griffin | A.J. Griffin | Ricky Romero | | 478 | 470 | 8 |
| 2012-07-26 | vs OAK | 98 | L 10-4 | 45-53 | 4 | 39,003 | Aaron Laffey | Tom Milone | Brandon Lyon | Tom Milone | | 488 | 474 | 14 |
| 2012-07-27 | vs DET | 99 | W 8-3 | 46-53 | 4 | 33,962 | Carlos Villanueva | Rick Porcello | Carlos Villanueva | Rick Porcello | | 496 | 477 | 19 |
| 2012-07-28 | vs DET | 100 | W 5-1 | 47-53 | 4 | 41,832 | Henderson Alvarez | Anibal Sanchez | Henderson Alvarez | Anibal Sanchez | | 501 | 478 | 23 |
| 2012-07-29 | vs DET | 101 | L 1-4 | 47-54 | 4 | 35,975 | Brett Cecil | Doug Fister | Doug Fister | Brett Cecil | Jose Valverde | 502 | 482 | 20 |
| 2012-07-30 | @ SEA | 102 | L 1-4 | 47-55 | 4 | 22,443 | Ricky Romero | Hisashi Iwakuma | Hisashi Iwakuma | Ricky Romero | Lucas Luetge | 503 | 486 | 17 |
| 2012-07-31 | @ SEA | 103 | L 2-7 | 47-56 | 5 | 21,434 | Aaron Laffey | Jason Vargas | Jason Vargas | Aaron Laffey | | 505 | 493 | 12 |
| 2012-08-01 | @ SEA | 104 | L 3-5 | 47-57 | 5 | 22,537 | Carlos Villanueva | Blake Beavan | Blake Beavan | Carlos Villanueva | Tom Wilhelmsen | 508 | 498 | 10 |
| 2012-08-02 | @ OAK | 105 | L 1-4 | 47-58 | 5 | 10,823 | Henderson Alvarez | Bartolo Colon | Bartolo Colon | Henderson Alvarez | Ryan Cook | 509 | 502 | 7 |
| 2012-08-03 | @ OAK | 106 | L 4-5 | 47-59 | 5 | 30,169 | Brett Cecil | Dan Straily | Travis Blackley | Aaron Loup | | 513 | 507 | 6 |
| 2012-08-04 | @ OAK | 107 | W 3-1 | 48-59 | 4 | 17,121 | Ricky Romero | A.J. Griffin | Jesse Chavez | Jerry Blevins | Darren Oliver | 516 | 508 | 8 |
| 2012-08-05 | @ OAK | 108 | W 6-5 | 49-59 | 4 | 18,308 | Aaron Laffey | Tom Milone | Aaron Laffey | Tom Milone | Casey Janssen | 522 | 513 | 9 |
| 2012-08-07 | @ TBA | 109 | L 1-4 | 49-60 | 5 | 13,823 | J.A. Happ | James Shields | James Shields | J.A. Happ | Fernando Rodney | 523 | 517 | 6 |
| 2012-08-08 | @ TBA | 110 | L 2-3 | 49-61 | 5 | 13,441 | Carlos Villanueva | Alex Cobb | Alex Cobb | Carlos Villanueva | Fernando Rodney | 525 | 520 | 5 |
| 2012-08-09 | @ TBA | 111 | L 1-7 | 49-62 | 5 | 23,462 | Henderson Alvarez | Matt Moore | Matt Moore | Henderson Alvarez | | 526 | 527 | -1 |
| 2012-08-10 | vs NYA | 112 | W 4-10 | 50-62 | 5 | 41,610 | Ricky Romero | Freddy Garcia | Freddy Garcia | Ricky Romero | | 530 | 537 | -7 |
| 2012-08-11 | vs NYA | 113 | L 2-5 | 50-63 | 5 | 45,582 | Aaron Laffey | Ivan Nova | Ivan Nova | Aaron Laffey | Rafael Soriano | 532 | 542 | -10 |
| 2012-08-12 | vs NYA | 114 | L 10-7 | 50-64 | 5 | 43,924 | J.A. Happ | Phil Hughes | J.A. Happ | Phil Hughes | Casey Janssen | 542 | 549 | -7 |
| 2012-08-13 | vs CHA | 115 | W 3-2 | 51-64 | 5 | 16,828 | Carlos Villanueva | Jake Peavy | Steve Delabar | Leyson Septimo | | 545 | 551 | -6 |
| 2012-08-14 | vs CHA | 116 | L 2-3 | 51-65 | 5 | 18,919 | Henderson Alvarez | Jose Quintana | Jose Quintana | Henderson Alvarez | Addison Reed | 547 | 554 | -7 |
| 2012-08-15 | vs CHA | 117 | L 5-9 | 51-66 | 5 | 20,119 | Ricky Romero | Gavin Floyd | Gavin Floyd | Ricky Romero | | 552 | 563 | -11 |
| 2012-08-16 | vs CHA | 118 | L 2-7 | 51-67 | 5 | 19,855 | Aaron Laffey | Francisco Liriano | Francisco Liriano | Aaron Laffey | | 554 | 570 | -16 |
| 2012-08-17 | vs TEX | 119 | W 3-2 | 52-67 | 5 | 26,816 | J.A. Happ | Yu Darvish | J.A. Happ | Yu Darvish | Casey Janssen | 557 | 572 | -15 |
| 2012-08-18 | vs TEX | 120 | L 1-2 | 52-68 | 5 | 30,033 | Carlos Villanueva | Roy Oswalt | Michael Kirkman | Carlos Villanueva | Joe Nathan | 558 | 574 | -16 |
| 2012-08-19 | vs TEX | 121 | W 2-11 | 53-68 | 5 | 35,701 | Henderson Alvarez | Matt Harrison | Matt Harrison | Henderson Alvarez | | 560 | 585 | -25 |
| 2012-08-21 | @ DET | 122 | L 3-5 | 53-69 | 5 | 39,499 | Ricky Romero | Max Scherzer | Max Scherzer | Ricky Romero | Jose Valverde | 563 | 590 | -27 |
| 2012-08-22 | @ DET | 123 | L 2-3 | 53-70 | 5 | 37,225 | Aaron Laffey | Anibal Sanchez | Anibal Sanchez | Aaron Laffey | Jose Valverde | 565 | 593 | -28 |
| 2012-08-23 | @ DET | 124 | L 2-3 | 53-71 | 5 | 39,910 | J.A. Happ | Justin Verlander | Joaquin Benoit | Chad Jenkins | | 567 | 596 | -29 |
| 2012-08-24 | @ BAL | 125 | L 4-6 | 53-72 | 5 | 25,754 | Carlos Villanueva | Zachary Britton | Zachary Britton | Carlos Villanueva | Jim Johnson | 571 | 602 | -31 |
| 2012-08-25 | @ BAL | 126 | L 2-8 | 53-73 | 5 | 25,082 | Brandon Morrow | Steve Johnson | Steve Johnson | Brandon Morrow | | 573 | 610 | -37 |
| 2012-08-27 | @ NYA | 127 | W 8-7 | 54-73 | 5 | 42,962 | Henderson Alvarez | David Phelps | Darren Oliver | Derek Lowe | | 581 | 617 | -36 |
| 2012-08-28 | @ NYA | 128 | L 1-2 | 54-74 | 5 | 42,472 | Ricky Romero | Phil Hughes | Phil Hughes | Ricky Romero | Rafael Soriano | 582 | 619 | -37 |
| 2012-08-29 | @ NYA | 129 | W 8-5 | 55-74 | 5 | 46,010 | J.A. Happ | CC Sabathia | J.A. Happ | CC Sabathia | Casey Janssen | 590 | 624 | -34 |
| 2012-08-30 | vs TBA | 130 | W 2-0 | 56-74 | 5 | 22,711 | Carlos Villanueva | Matt Moore | Carlos Villanueva | Matt Moore | Casey Janssen | 592 | 624 | -32 |
| 2012-08-31 | vs TBA | 131 | W 2-1 | 57-74 | 5 | 20,158 | Brandon Morrow | Jeremy Hellickson | Brandon Morrow | Jeremy Hellickson | Casey Janssen | 594 | 625 | -31 |
| 2012-09-01 | vs TBA | 132 | L 4-5 | 57-75 | 5 | 20,478 | Henderson Alvarez | Jeff Niemann | Wade Davis | Henderson Alvarez | Fernando Rodney | 598 | 630 | -32 |
| 2012-09-02 | vs TBA | 133 | L 4-9 | 57-76 | 5 | 18,568 | Ricky Romero | David Price | David Price | Ricky Romero | | 602 | 639 | -37 |
| 2012-09-03 | vs BAL | 134 | L 0-4 | 57-77 | 5 | 17,220 | J.A. Happ | Joe Saunders | Joe Saunders | J.A. Happ | | 602 | 643 | -41 |
| 2012-09-04 | vs BAL | 135 | L 0-12 | 57-78 | 5 | 13,556 | Carlos Villanueva | Zachary Britton | Zachary Britton | Carlos Villanueva | | 602 | 655 | -53 |
| 2012-09-05 | vs BAL | 136 | W 6-4 | 58-78 | 5 | 14,458 | Brandon Morrow | Miguel Gonzalez | Steve Delabar | Miguel Gonzalez | | 608 | 659 | -51 |
| 2012-09-07 | @ BOS | 137 | W 7-5 | 59-78 | 5 | 37,156 | Henderson Alvarez | Felix Doubront | Henderson Alvarez | Felix Doubront | | 615 | 664 | -49 |
| 2012-09-08 | @ BOS | 138 | W 9-2 | 60-78 | 5 | 37,107 | Aaron Laffey | Daisuke Matsuzaka | Brad Lincoln | Daisuke Matsuzaka | | 624 | 666 | -42 |
| 2012-09-09 | @ BOS | 139 | W 4-3 | 61-78 | 4 | 37,226 | Carlos Villanueva | Clay Buchholz | Brandon Lyon | Clay Buchholz | Casey Janssen | 628 | 669 | -41 |
| 2012-09-11 | vs SEA | 140 | L 3-4 | 61-79 | 5 | 12,935 | Brandon Morrow | Erasmo Ramirez | Erasmo Ramirez | Brandon Morrow | Tom Wilhelmsen | 631 | 673 | -42 |
| 2012-09-12 | vs SEA | 141 | L 2-3 | 61-80 | 5 | 13,519 | Ricky Romero | Kevin Millwood | Kevin Millwood | Ricky Romero | Tom Wilhelmsen | 633 | 676 | -43 |
| 2012-09-13 | vs SEA | 142 | W 8-3 | 62-80 | 4 | 13,756 | Henderson Alvarez | Felix Hernandez | Henderson Alvarez | Felix Hernandez | | 641 | 679 | -38 |
| 2012-09-14 | vs BOS | 143 | L 5-8 | 62-81 | 5 | 21,888 | Aaron Laffey | Daisuke Matsuzaka | Chris Carpenter | Darren Oliver | Andrew Bailey | 646 | 687 | -41 |
| 2012-09-15 | vs BOS | 144 | L 2-3 | 62-82 | 5 | 27,325 | Carlos Villanueva | Clay Buchholz | Craig Breslow | Steve Delabar | Andrew Bailey | 648 | 690 | -42 |
| 2012-09-16 | vs BOS | 145 | W 5-0 | 63-82 | 5 | 21,698 | Brandon Morrow | Jon Lester | Brandon Lyon | Jon Lester | | 653 | 690 | -37 |
| 2012-09-19 | @ NYA | 146 | L 2-4 | 63-84 | 7 | 39,859 | Henderson Alvarez | Andy Pettitte | Andy Pettitte | Henderson Alvarez | Rafael Soriano | 655 | 694 | -39 |
| 2012-09-19 | @ NYA | 147 | L 1-2 | 63-84 | 7 | 39,997 | Ricky Romero | David Phelps | Cody Eppley | Steve Delabar | Rafael Soriano | 656 | 696 | -40 |
| 2012-09-20 | @ NYA | 148 | W 7-10 | 64-84 | 5 | 40,511 | Aaron Laffey | Phil Hughes | Phil Hughes | Aaron Laffey | David Robertson | 663 | 706 | -43 |
| 2012-09-21 | @ TBA | 149 | L 1-12 | 64-85 | 5 | 14,187 | Carlos Villanueva | James Shields | James Shields | Carlos Villanueva | | 664 | 718 | -54 |
| 2012-09-22 | @ TBA | 150 | W 5-11 | 65-85 | 5 | 15,699 | Brandon Morrow | Matt Moore | Burke Badenhop | Brandon Morrow | | 669 | 729 | -60 |
| 2012-09-23 | @ TBA | 151 | L 0-3 | 65-86 | 5 | 18,985 | Chad Jenkins | Jeremy Hellickson | Jeremy Hellickson | Chad Jenkins | Fernando Rodney | 669 | 732 | -63 |
| 2012-09-24 | @ BAL | 152 | L 1-4 | 65-87 | 7 | 0 | Henderson Alvarez | Steve Johnson | Steve Johnson | Henderson Alvarez | Jim Johnson | 670 | 736 | -66 |
| 2012-09-24 | @ BAL | 153 | W 9-5 | 65-87 | 7 | 31,015 | Ricky Romero | Wei-Yin Chen | Ricky Romero | Wei-Yin Chen | | 679 | 741 | -62 |
| 2012-09-25 | @ BAL | 154 | W 4-0 | 67-87 | 5 | 30,205 | Aaron Laffey | Joe Saunders | Aaron Laffey | Joe Saunders | | 683 | 741 | -58 |
| 2012-09-26 | @ BAL | 155 | W 2-12 | 68-87 | 4 | 26,513 | Carlos Villanueva | Miguel Gonzalez | Miguel Gonzalez | Carlos Villanueva | | 685 | 753 | -68 |
| 2012-09-27 | vs NYA | 156 | W 6-0 | 69-87 | 4 | 23,060 | Brandon Morrow | Ivan Nova | Brandon Morrow | Ivan Nova | | 691 | 753 | -62 |
| 2012-09-28 | vs NYA | 157 | W 4-11 | 70-87 | 4 | 25,785 | Chad Jenkins | Hiroki Kuroda | Hiroki Kuroda | Chad Jenkins | | 695 | 764 | -69 |
| 2012-09-29 | vs NYA | 158 | W 3-2 | 71-87 | 4 | 36,139 | Ricky Romero | Andy Pettitte | Shawn Hill | Andy Pettitte | Casey Janssen | 698 | 766 | -68 |
| 2012-09-30 | vs NYA | 159 | L 6-9 | 71-88 | 4 | 31,418 | Henderson Alvarez | Phil Hughes | Boone Logan | Darren Oliver | | 704 | 775 | -71 |
| 2012-10-01 | vs MIN | 160 | W 6-5 | 72-88 | 4 | 12,359 | Aaron Laffey | Esmerling Vasquez | Brandon Lyon | Brian Duensing | | 710 | 780 | -70 |
| 2012-10-02 | vs MIN | 161 | W 4-3 | 73-88 | 4 | 13,930 | Chad Jenkins | Anthony Swarzak | Chad Jenkins | Anthony Swarzak | Casey Janssen | 714 | 783 | -69 |
| 2012-10-03 | vs MIN | 162 | W 2-1 | 74-88 | 4 | 19,769 | Brandon Morrow | Scott Diamond | Brandon Morrow | Scott Diamond | Brandon Lyon | 716 | 784 | -68 |