| 2012-04-06 | vs CHA | 1 | W 3-2 | 1-0 | 2 | 49,085 | Colby Lewis | John Danks | Colby Lewis | John Danks | Joe Nathan | 3 | 2 | 1 |
| 2012-04-07 | vs CHA | 2 | L 3-4 | 1-1 | 3 | 47,867 | Derek Holland | Jake Peavy | Matt Thornton | Joe Nathan | Hector Santiago | 6 | 6 | 0 |
| 2012-04-08 | vs CHA | 3 | W 5-0 | 2-1 | 2 | 45,368 | Matt Harrison | Gavin Floyd | Matt Harrison | Gavin Floyd | | 11 | 6 | 5 |
| 2012-04-09 | vs SEA | 4 | L 11-5 | 2-2 | 3 | 42,003 | Yu Darvish | Hector Noesi | Yu Darvish | Hector Noesi | | 22 | 11 | 11 |
| 2012-04-10 | vs SEA | 5 | W 1-0 | 3-2 | 2 | 25,753 | Neftali Feliz | Blake Beavan | Neftali Feliz | Blake Beavan | Joe Nathan | 23 | 11 | 12 |
| 2012-04-11 | vs SEA | 6 | L 3-4 | 3-3 | 2 | 32,342 | Colby Lewis | Kevin Millwood | Lucas Luetge | Joe Nathan | Brandon League | 26 | 15 | 11 |
| 2012-04-12 | vs SEA | 7 | W 5-3 | 4-3 | 2 | 31,513 | Derek Holland | Jason Vargas | Derek Holland | Jason Vargas | Mike Adams | 31 | 18 | 13 |
| 2012-04-13 | @ MIN | 8 | W 4-1 | 5-3 | 1 | 31,400 | Matt Harrison | Anthony Swarzak | Matt Harrison | Anthony Swarzak | Alexi Ogando | 35 | 19 | 16 |
| 2012-04-14 | @ MIN | 9 | W 6-2 | 6-3 | 1 | 35,854 | Yu Darvish | Nick Blackburn | Robbie Ross | Brian Duensing | | 41 | 21 | 20 |
| 2012-04-15 | @ MIN | 10 | W 4-3 | 7-3 | 1 | 32,093 | Neftali Feliz | Liam Hendriks | Robbie Ross | Glen Perkins | Joe Nathan | 45 | 24 | 21 |
| 2012-04-17 | @ BOS | 11 | L 18-3 | 7-4 | 1 | 38,229 | Colby Lewis | Jon Lester | Colby Lewis | Jon Lester | | 63 | 27 | 36 |
| 2012-04-18 | @ BOS | 12 | W 6-3 | 8-4 | 1 | 37,967 | Derek Holland | Josh Beckett | Derek Holland | Josh Beckett | | 69 | 30 | 39 |
| 2012-04-19 | @ DET | 13 | L 10-3 | 8-5 | 1 | 30,029 | Yu Darvish | Adam Wilk | Yu Darvish | Adam Wilk | | 79 | 33 | 46 |
| 2012-04-21 | @ DET | 14 | L 10-4 | 8-7 | 3 | 41,427 | Matt Harrison | Rick Porcello | Matt Harrison | Rick Porcello | | 89 | 37 | 52 |
| 2012-04-21 | @ DET | 15 | L 2-3 | 8-7 | 3 | 35,001 | Neftali Feliz | Justin Verlander | Justin Verlander | Neftali Feliz | Jose Valverde | 91 | 40 | 51 |
| 2012-04-22 | @ DET | 16 | W 3-2 | 9-7 | 1 | 36,255 | Colby Lewis | Drew Smyly | Robbie Ross | Thad Weber | Joe Nathan | 94 | 42 | 52 |
| 2012-04-23 | vs NYA | 17 | L 4-7 | 9-8 | 1 | 48,234 | Derek Holland | CC Sabathia | CC Sabathia | Derek Holland | Mariano Rivera | 98 | 49 | 49 |
| 2012-04-24 | vs NYA | 18 | W 2-0 | 10-8 | 1 | 47,085 | Yu Darvish | Hiroki Kuroda | Yu Darvish | Hiroki Kuroda | Joe Nathan | 100 | 49 | 51 |
| 2012-04-25 | vs NYA | 19 | W 7-3 | 11-8 | 1 | 47,942 | Scott Feldman | Phil Hughes | Robbie Ross | Phil Hughes | | 107 | 52 | 55 |
| 2012-04-27 | vs TBA | 20 | L 4-8 | 11-9 | 2 | 47,496 | Matt Harrison | James Shields | James Shields | Matt Harrison | | 111 | 60 | 51 |
| 2012-04-28 | vs TBA | 21 | W 7-2 | 12-9 | 1 | 49,197 | Colby Lewis | Jeff Niemann | Colby Lewis | Jeff Niemann | | 118 | 62 | 56 |
| 2012-04-29 | vs TBA | 22 | L 2-5 | 12-10 | 1 | 43,475 | Derek Holland | David Price | David Price | Derek Holland | Fernando Rodney | 120 | 67 | 53 |
| 2012-04-30 | @ TOR | 23 | W 4-1 | 13-10 | 1 | 21,945 | Yu Darvish | Kyle Drabek | Yu Darvish | Kyle Drabek | Joe Nathan | 124 | 68 | 56 |
| 2012-05-01 | @ TOR | 24 | L 7-8 | 13-11 | 1 | 18,774 | Neftali Feliz | Drew Hutchison | Francisco Cordero | Mike Adams | | 131 | 76 | 55 |
| 2012-05-02 | @ TOR | 25 | W 5-11 | 14-11 | 1 | 25,123 | Matt Harrison | Ricky Romero | Ricky Romero | Matt Harrison | | 136 | 87 | 49 |
| 2012-05-04 | @ CLE | 26 | L 3-6 | 14-12 | 1 | 16,147 | Colby Lewis | Jeanmar Gomez | Jeanmar Gomez | Colby Lewis | Chris Perez | 139 | 93 | 46 |
| 2012-05-05 | @ CLE | 27 | W 5-2 | 15-12 | 1 | 21,307 | Derek Holland | Derek Lowe | Alexi Ogando | Joe Smith | Joe Nathan | 144 | 95 | 49 |
| 2012-05-06 | @ CLE | 28 | L 2-4 | 15-13 | 2 | 18,171 | Yu Darvish | Ubaldo Jimenez | Ubaldo Jimenez | Yu Darvish | Chris Perez | 146 | 99 | 47 |
| 2012-05-07 | @ BAL | 29 | L 14-3 | 15-14 | 2 | 11,938 | Matt Harrison | Brian Matusz | Matt Harrison | Brian Matusz | | 160 | 102 | 58 |
| 2012-05-08 | @ BAL | 30 | L 10-3 | 15-15 | 2 | 11,263 | Neftali Feliz | Jake Arrieta | Neftali Feliz | Jake Arrieta | | 170 | 105 | 65 |
| 2012-05-10 | @ BAL | 31 | L 5-6 | 15-16 | 5 | 0 | Colby Lewis | Wei-Yin Chen | Wei-Yin Chen | Colby Lewis | Jim Johnson | 175 | 111 | 64 |
| 2012-05-10 | @ BAL | 32 | W 7-3 | 15-16 | 5 | 19,250 | Derek Holland | Tommy Hunter | Derek Holland | Tommy Hunter | | 182 | 114 | 68 |
| 2012-05-11 | vs ANA | 33 | L 10-3 | 16-17 | 3 | 48,201 | Yu Darvish | C.J. Wilson | Yu Darvish | C.J. Wilson | | 192 | 117 | 75 |
| 2012-05-12 | vs ANA | 34 | L 2-4 | 16-18 | 3 | 47,699 | Matt Harrison | C.J. Wilson | David Carpenter | Matt Harrison | Scott Downs | 194 | 121 | 73 |
| 2012-05-13 | vs ANA | 35 | L 13-6 | 16-19 | 4 | 46,669 | Neftali Feliz | Jered Weaver | Neftali Feliz | Jered Weaver | | 207 | 127 | 80 |
| 2012-05-14 | vs KCA | 36 | L 1-3 | 16-20 | 4 | 38,702 | Scott Feldman | Bruce Chen | Bruce Chen | Scott Feldman | Jonathan Broxton | 208 | 130 | 78 |
| 2012-05-15 | vs KCA | 37 | L 4-7 | 16-21 | 4 | 37,210 | Colby Lewis | Vin Mazzaro | Vin Mazzaro | Colby Lewis | | 212 | 137 | 75 |
| 2012-05-16 | vs OAK | 38 | W 4-1 | 17-21 | 3 | 46,370 | Yu Darvish | Tom Milone | Yu Darvish | Tom Milone | Joe Nathan | 216 | 138 | 78 |
| 2012-05-17 | vs OAK | 39 | L 4-5 | 17-22 | 3 | 47,182 | Matt Harrison | Brandon McCarthy | Ryan Cook | Mike Adams | Brian Fuentes | 220 | 143 | 77 |
| 2012-05-18 | @ HOU | 40 | W 4-1 | 18-22 | 3 | 34,715 | Neftali Feliz | Wandy Rodriguez | Robbie Ross | Wandy Rodriguez | Joe Nathan | 224 | 144 | 80 |
| 2012-05-19 | @ HOU | 41 | L 5-6 | 18-23 | 3 | 42,673 | Derek Holland | Lucas Harrell | Lucas Harrell | Derek Holland | Brett Myers | 229 | 150 | 79 |
| 2012-05-20 | @ HOU | 42 | W 6-1 | 19-23 | 3 | 35,873 | Colby Lewis | Jordan Lyles | Colby Lewis | Jordan Lyles | | 235 | 151 | 84 |
| 2012-05-21 | @ SEA | 43 | L 1-6 | 19-24 | 4 | 18,672 | Yu Darvish | Felix Hernandez | Felix Hernandez | Yu Darvish | | 236 | 157 | 79 |
| 2012-05-22 | @ SEA | 44 | W 3-1 | 20-24 | 3 | 15,604 | Matt Harrison | Hector Noesi | Matt Harrison | Hector Noesi | Joe Nathan | 239 | 158 | 81 |
| 2012-05-23 | @ SEA | 45 | L 3-5 | 20-25 | 4 | 23,097 | Scott Feldman | Kevin Millwood | Kevin Millwood | Scott Feldman | Brandon League | 242 | 163 | 79 |
| 2012-05-25 | vs TOR | 46 | L 14-3 | 20-26 | 4 | 46,789 | Derek Holland | Brandon Morrow | Derek Holland | Brandon Morrow | | 256 | 166 | 90 |
| 2012-05-26 | vs TOR | 47 | W 8-7 | 21-26 | 3 | 47,430 | Colby Lewis | Henderson Alvarez | Yoshinori Tateyama | Jason Frasor | | 264 | 173 | 91 |
| 2012-05-27 | vs TOR | 48 | L 12-6 | 21-27 | 3 | 46,637 | Yu Darvish | Kyle Drabek | Yu Darvish | Kyle Drabek | | 276 | 179 | 97 |
| 2012-05-28 | vs SEA | 49 | W 4-2 | 22-27 | 3 | 41,384 | Matt Harrison | Kevin Millwood | Matt Harrison | Steve Delabar | Joe Nathan | 280 | 181 | 99 |
| 2012-05-29 | vs SEA | 50 | W 3-10 | 23-27 | 3 | 34,531 | Scott Feldman | Jason Vargas | Jason Vargas | Scott Feldman | | 283 | 191 | 92 |
| 2012-05-30 | vs SEA | 51 | W 8-21 | 24-27 | 2 | 43,580 | Derek Holland | Blake Beavan | Blake Beavan | Derek Holland | Hisashi Iwakuma | 291 | 212 | 79 |
| 2012-06-01 | @ ANA | 52 | L 2-4 | 24-28 | 2 | 40,080 | Colby Lewis | Jerome Williams | Jerome Williams | Colby Lewis | Ernesto Frieri | 293 | 216 | 77 |
| 2012-06-02 | @ ANA | 53 | L 2-3 | 24-29 | 3 | 44,227 | Yu Darvish | C.J. Wilson | Bobby Cassevah | Yu Darvish | Ernesto Frieri | 295 | 219 | 76 |
| 2012-06-03 | @ ANA | 54 | W 7-3 | 25-29 | 2 | 42,465 | Matt Harrison | Dan Haren | Matt Harrison | Dan Haren | | 302 | 222 | 80 |
| 2012-06-04 | @ OAK | 55 | L 1-12 | 25-30 | 3 | 10,120 | Scott Feldman | Jarrod Parker | Jarrod Parker | Scott Feldman | | 303 | 234 | 69 |
| 2012-06-05 | @ OAK | 56 | W 6-3 | 26-30 | 2 | 11,861 | Derek Holland | Travis Blackley | Derek Holland | Travis Blackley | Joe Nathan | 309 | 237 | 72 |
| 2012-06-06 | @ OAK | 57 | L 0-2 | 26-31 | 3 | 15,044 | Colby Lewis | Bartolo Colon | Bartolo Colon | Colby Lewis | Brian Fuentes | 309 | 239 | 70 |
| 2012-06-07 | @ OAK | 58 | L 1-7 | 26-32 | 3 | 14,779 | Yu Darvish | Brandon McCarthy | Brandon McCarthy | Yu Darvish | | 310 | 246 | 64 |
| 2012-06-08 | @ SFN | 59 | W 5-0 | 27-32 | 3 | 41,163 | Matt Harrison | Barry Zito | Matt Harrison | Barry Zito | | 315 | 246 | 69 |
| 2012-06-09 | @ SFN | 60 | L 2-5 | 27-33 | 3 | 41,704 | Scott Feldman | Ryan Vogelsong | Ryan Vogelsong | Scott Feldman | Santiago Casilla | 317 | 251 | 66 |
| 2012-06-10 | @ SFN | 61 | W 5-0 | 28-33 | 2 | 42,418 | Alexi Ogando | Tim Lincecum | Robbie Ross | Tim Lincecum | | 322 | 251 | 71 |
| 2012-06-12 | vs ARI | 62 | W 9-1 | 29-33 | 2 | 39,140 | Colby Lewis | Ian Kennedy | Colby Lewis | Ian Kennedy | | 331 | 252 | 79 |
| 2012-06-13 | vs ARI | 63 | W 1-0 | 30-33 | 2 | 45,866 | Matt Harrison | Wade Miley | Mike Adams | Wade Miley | Joe Nathan | 332 | 252 | 80 |
| 2012-06-14 | vs ARI | 64 | W 3-11 | 31-33 | 2 | 40,855 | Scott Feldman | Daniel Hudson | Daniel Hudson | Scott Feldman | | 335 | 263 | 72 |
| 2012-06-15 | vs HOU | 65 | W 6-2 | 32-33 | 2 | 47,430 | Yu Darvish | Jordan Lyles | Yu Darvish | Jordan Lyles | | 341 | 265 | 76 |
| 2012-06-16 | vs HOU | 66 | W 8-3 | 33-33 | 2 | 48,288 | Justin Grimm | Lucas Harrell | Justin Grimm | Lucas Harrell | | 349 | 268 | 81 |
| 2012-06-17 | vs HOU | 67 | W 9-3 | 34-33 | 2 | 46,320 | Colby Lewis | Dallas Keuchel | Colby Lewis | Fernando Rodriguez | | 358 | 271 | 87 |
| 2012-06-18 | @ SDN | 68 | W 2-1 | 35-33 | 2 | 29,315 | Matt Harrison | Jason Marquis | Matt Harrison | Jason Marquis | Joe Nathan | 360 | 272 | 88 |
| 2012-06-19 | @ SDN | 69 | W 7-3 | 36-33 | 2 | 25,889 | Scott Feldman | Edinson Volquez | Scott Feldman | Edinson Volquez | | 367 | 275 | 92 |
| 2012-06-20 | @ SDN | 70 | W 4-2 | 37-33 | 2 | 23,942 | Yu Darvish | Anthony Bass | Yu Darvish | Dale Thayer | Joe Nathan | 371 | 277 | 94 |
| 2012-06-22 | vs COL | 71 | W 4-1 | 38-33 | 2 | 46,964 | Roy Oswalt | Christian Friedrich | Roy Oswalt | Christian Friedrich | Joe Nathan | 375 | 278 | 97 |
| 2012-06-23 | vs COL | 72 | W 7-11 | 39-33 | 2 | 42,516 | Colby Lewis | Josh Outman | Rex Brothers | Colby Lewis | | 382 | 289 | 93 |
| 2012-06-24 | vs COL | 73 | W 4-2 | 40-33 | 2 | 45,407 | Matt Harrison | Alex White | Matt Harrison | Alex White | | 386 | 291 | 95 |
| 2012-06-25 | vs DET | 74 | L 2-8 | 40-34 | 2 | 36,920 | Justin Grimm | Rick Porcello | Rick Porcello | Justin Grimm | | 388 | 299 | 89 |
| 2012-06-26 | vs DET | 75 | W 7-5 | 41-34 | 2 | 39,561 | Yu Darvish | Drew Smyly | Yu Darvish | Drew Smyly | Joe Nathan | 395 | 304 | 91 |
| 2012-06-27 | vs DET | 76 | L 13-9 | 41-35 | 2 | 43,379 | Roy Oswalt | Doug Fister | Roy Oswalt | Doug Fister | | 408 | 313 | 95 |
| 2012-06-28 | vs OAK | 77 | W 7-6 | 42-35 | 2 | 33,927 | Scott Feldman | Tyson Ross | Scott Feldman | Tyson Ross | Joe Nathan | 415 | 319 | 96 |
| 2012-06-29 | vs OAK | 78 | W 4-3 | 43-35 | 2 | 46,013 | Matt Harrison | A.J. Griffin | Matt Harrison | Grant Balfour | Tanner Scheppers | 419 | 322 | 97 |
| 2012-06-30 | vs OAK | 79 | W 7-2 | 44-35 | 2 | 46,711 | Martin Perez | Tom Milone | Martin Perez | Tom Milone | | 426 | 324 | 102 |
| 2012-07-01 | vs OAK | 80 | L 1-3 | 44-36 | 2 | 45,741 | Yu Darvish | Travis Blackley | Travis Blackley | Yu Darvish | Ryan Cook | 427 | 327 | 100 |
| 2012-07-03 | @ CHA | 81 | W 2-19 | 45-36 | 2 | 30,183 | Roy Oswalt | Chris Sale | Chris Sale | Roy Oswalt | | 429 | 346 | 83 |
| 2012-07-04 | @ CHA | 82 | L 4-5 | 45-37 | 2 | 30,271 | Scott Feldman | Dylan Axelrod | Addison Reed | Mike Adams | | 433 | 351 | 82 |
| 2012-07-05 | @ CHA | 83 | L 1-2 | 45-38 | 2 | 21,288 | Matt Harrison | Jose Quintana | Jose Quintana | Matt Harrison | Addison Reed | 434 | 353 | 81 |
| 2012-07-06 | vs MIN | 84 | L 1-5 | 45-39 | 2 | 47,240 | Martin Perez | Francisco Liriano | Francisco Liriano | Martin Perez | | 435 | 358 | 77 |
| 2012-07-07 | vs MIN | 85 | W 4-3 | 46-39 | 2 | 47,067 | Derek Holland | Samuel Deduno | Joe Nathan | Kyle Waldrop | | 439 | 361 | 78 |
| 2012-07-08 | vs MIN | 86 | W 4-3 | 47-39 | 2 | 43,268 | Roy Oswalt | Cole De Vries | Scott Feldman | Alex Burnett | | 443 | 364 | 79 |
| 2012-07-13 | @ SEA | 87 | W 3-2 | 48-39 | 2 | 23,721 | Derek Holland | Kevin Millwood | Derek Holland | Kevin Millwood | Joe Nathan | 446 | 366 | 80 |
| 2012-07-14 | @ SEA | 88 | L 0-7 | 48-40 | 2 | 29,951 | Yu Darvish | Felix Hernandez | Felix Hernandez | Yu Darvish | | 446 | 373 | 73 |
| 2012-07-15 | @ SEA | 89 | W 4-0 | 49-40 | 2 | 27,378 | Matt Harrison | Hisashi Iwakuma | Matt Harrison | Hisashi Iwakuma | | 450 | 373 | 77 |
| 2012-07-17 | @ OAK | 90 | W 6-1 | 50-40 | 2 | 15,115 | Roy Oswalt | Bartolo Colon | Roy Oswalt | Bartolo Colon | | 456 | 374 | 82 |
| 2012-07-18 | @ OAK | 91 | L 3-4 | 50-41 | 2 | 20,249 | Colby Lewis | Travis Blackley | Ryan Cook | Michael Kirkman | | 459 | 378 | 81 |
| 2012-07-20 | @ ANA | 92 | L 1-6 | 50-42 | 2 | 43,936 | Derek Holland | Jered Weaver | Jered Weaver | Derek Holland | | 460 | 384 | 76 |
| 2012-07-21 | @ ANA | 93 | W 9-2 | 51-42 | 1 | 39,086 | Yu Darvish | Ervin Santana | Yu Darvish | Ervin Santana | | 469 | 386 | 83 |
| 2012-07-22 | @ ANA | 94 | L 4-7 | 51-43 | 2 | 42,160 | Matt Harrison | Dan Haren | Dan Haren | Matt Harrison | | 473 | 393 | 80 |
| 2012-07-23 | vs BOS | 95 | W 9-1 | 52-43 | 2 | 44,132 | Scott Feldman | Felix Doubront | Scott Feldman | Felix Doubront | | 482 | 394 | 88 |
| 2012-07-24 | vs BOS | 96 | L 1-2 | 52-44 | 2 | 41,237 | Martin Perez | Clay Buchholz | Vicente Padilla | Joe Nathan | Alfredo Aceves | 483 | 396 | 87 |
| 2012-07-25 | vs BOS | 97 | W 5-3 | 53-44 | 1 | 44,104 | Derek Holland | Josh Beckett | Derek Holland | Josh Beckett | Joe Nathan | 488 | 399 | 89 |
| 2012-07-27 | vs CHA | 98 | L 5-9 | 53-45 | 2 | 47,638 | Yu Darvish | Chris Sale | Chris Sale | Yu Darvish | | 493 | 408 | 85 |
| 2012-07-28 | vs CHA | 99 | L 2-5 | 53-46 | 3 | 47,580 | Matt Harrison | Philip Humber | Philip Humber | Matt Harrison | | 495 | 413 | 82 |
| 2012-07-29 | vs CHA | 100 | W 2-0 | 54-46 | 1 | 46,744 | Scott Feldman | Gavin Floyd | Scott Feldman | Gavin Floyd | Joe Nathan | 497 | 413 | 84 |
| 2012-07-30 | vs ANA | 101 | W 8-15 | 55-46 | 1 | 36,111 | Roy Oswalt | Ervin Santana | Ervin Santana | Roy Oswalt | Jerome Williams | 505 | 428 | 77 |
| 2012-07-31 | vs ANA | 102 | L 2-6 | 55-47 | 1 | 34,918 | Derek Holland | Jered Weaver | Jered Weaver | Derek Holland | | 507 | 434 | 73 |
| 2012-08-01 | vs ANA | 103 | W 11-10 | 56-47 | 1 | 42,832 | Yu Darvish | Garrett Richards | Joe Nathan | Jason Isringhausen | | 518 | 444 | 74 |
| 2012-08-02 | vs ANA | 104 | L 15-9 | 56-48 | 1 | 40,281 | Ryan Dempster | C.J. Wilson | Roy Oswalt | David Carpenter | | 533 | 453 | 80 |
| 2012-08-03 | @ KCA | 105 | W 5-3 | 57-48 | 1 | 26,889 | Matt Harrison | Jeremy Guthrie | Matt Harrison | Jeremy Guthrie | Alexi Ogando | 538 | 456 | 82 |
| 2012-08-04 | @ KCA | 106 | W 4-2 | 58-48 | 1 | 28,724 | Scott Feldman | Will Smith | Scott Feldman | Will Smith | Alexi Ogando | 542 | 458 | 84 |
| 2012-08-05 | @ KCA | 107 | L 6-7 | 58-49 | 1 | 22,007 | Derek Holland | Luke Hochevar | Greg Holland | Michael Kirkman | | 548 | 465 | 83 |
| 2012-08-06 | @ BOS | 108 | L 2-9 | 58-50 | 1 | 37,316 | Yu Darvish | Aaron Cook | Aaron Cook | Yu Darvish | | 550 | 474 | 76 |
| 2012-08-07 | @ BOS | 109 | W 6-3 | 59-50 | 1 | 38,416 | Ryan Dempster | Jon Lester | Ryan Dempster | Jon Lester | Joe Nathan | 556 | 477 | 79 |
| 2012-08-08 | @ BOS | 110 | L 10-9 | 59-51 | 1 | 37,716 | Matt Harrison | Josh Beckett | Alexi Ogando | Clayton Mortensen | Joe Nathan | 566 | 486 | 80 |
| 2012-08-10 | vs DET | 111 | L 2-6 | 59-52 | 2 | 47,255 | Scott Feldman | Max Scherzer | Max Scherzer | Scott Feldman | | 568 | 492 | 76 |
| 2012-08-11 | vs DET | 112 | W 2-1 | 60-52 | 1 | 48,303 | Derek Holland | Justin Verlander | Mike Adams | Brayan Villarreal | | 570 | 493 | 77 |
| 2012-08-12 | vs DET | 113 | W 8-3 | 61-52 | 1 | 45,752 | Yu Darvish | Rick Porcello | Yu Darvish | Rick Porcello | | 578 | 496 | 82 |
| 2012-08-13 | @ NYA | 114 | L 2-8 | 61-53 | 1 | 45,676 | Ryan Dempster | David Phelps | David Phelps | Ryan Dempster | Derek Lowe | 580 | 504 | 76 |
| 2012-08-14 | @ NYA | 115 | L 0-3 | 61-54 | 1 | 44,533 | Matt Harrison | Hiroki Kuroda | Hiroki Kuroda | Matt Harrison | | 580 | 507 | 73 |
| 2012-08-15 | @ NYA | 116 | L 2-3 | 61-55 | 2 | 45,921 | Scott Feldman | Freddy Garcia | Freddy Garcia | Scott Feldman | Rafael Soriano | 582 | 510 | 72 |
| 2012-08-16 | @ NYA | 117 | L 10-6 | 61-56 | 2 | 47,645 | Derek Holland | Ivan Nova | Tanner Scheppers | Boone Logan | | 592 | 516 | 76 |
| 2012-08-17 | @ TOR | 118 | L 2-3 | 61-57 | 3 | 26,816 | Yu Darvish | J.A. Happ | J.A. Happ | Yu Darvish | Casey Janssen | 594 | 519 | 75 |
| 2012-08-18 | @ TOR | 119 | W 2-1 | 62-57 | 3 | 30,033 | Roy Oswalt | Carlos Villanueva | Michael Kirkman | Carlos Villanueva | Joe Nathan | 596 | 520 | 76 |
| 2012-08-19 | @ TOR | 120 | L 11-2 | 62-58 | 3 | 35,701 | Matt Harrison | Henderson Alvarez | Matt Harrison | Henderson Alvarez | | 607 | 522 | 85 |
| 2012-08-20 | vs BAL | 121 | W 5-1 | 63-58 | 3 | 36,257 | Ryan Dempster | Miguel Gonzalez | Ryan Dempster | Miguel Gonzalez | | 612 | 523 | 89 |
| 2012-08-21 | vs BAL | 122 | L 3-5 | 63-59 | 3 | 32,146 | Scott Feldman | Chris Tillman | Chris Tillman | Scott Feldman | Jim Johnson | 615 | 528 | 87 |
| 2012-08-22 | vs BAL | 123 | L 12-3 | 63-60 | 3 | 40,714 | Derek Holland | Tommy Hunter | Derek Holland | Tommy Hunter | | 627 | 531 | 96 |
| 2012-08-23 | vs MIN | 124 | L 10-6 | 63-61 | 3 | 33,762 | Roy Oswalt | Scott Diamond | Mike Adams | Jared Burton | Joe Nathan | 637 | 537 | 100 |
| 2012-08-24 | vs MIN | 125 | W 8-0 | 64-61 | 3 | 45,823 | Matt Harrison | Samuel Deduno | Matt Harrison | Samuel Deduno | | 645 | 537 | 108 |
| 2012-08-25 | vs MIN | 126 | W 9-3 | 65-61 | 3 | 44,215 | Ryan Dempster | Brian Duensing | Ryan Dempster | Brian Duensing | | 654 | 540 | 114 |
| 2012-08-26 | vs MIN | 127 | L 5-6 | 65-62 | 3 | 37,785 | Scott Feldman | Cole De Vries | Cole De Vries | Scott Feldman | Glen Perkins | 659 | 546 | 113 |
| 2012-08-27 | vs TBA | 128 | W 6-5 | 66-62 | 3 | 29,453 | Derek Holland | David Price | Derek Holland | David Price | Joe Nathan | 665 | 551 | 114 |
| 2012-08-28 | vs TBA | 129 | W 1-0 | 67-62 | 3 | 30,700 | Yu Darvish | James Shields | Yu Darvish | James Shields | Joe Nathan | 666 | 551 | 115 |
| 2012-08-29 | vs TBA | 130 | L 4-8 | 67-63 | 3 | 36,176 | Matt Harrison | Alex Cobb | Jake McGee | Matt Harrison | | 670 | 559 | 111 |
| 2012-08-31 | @ CLE | 131 | W 5-3 | 68-63 | 3 | 16,700 | Ryan Dempster | Ubaldo Jimenez | Ryan Dempster | Ubaldo Jimenez | Joe Nathan | 675 | 562 | 113 |
| 2012-09-01 | @ CLE | 132 | L 3-4 | 68-64 | 3 | 17,218 | Scott Feldman | Jeanmar Gomez | Jeanmar Gomez | Scott Feldman | Vinnie Pestano | 678 | 566 | 112 |
| 2012-09-02 | @ CLE | 133 | W 8-3 | 69-64 | 3 | 19,474 | Derek Holland | Zach McAllister | Derek Holland | Zach McAllister | | 686 | 569 | 117 |
| 2012-09-03 | @ KCA | 134 | W 8-4 | 70-64 | 3 | 22,207 | Yu Darvish | Bruce Chen | Yu Darvish | Bruce Chen | | 694 | 573 | 121 |
| 2012-09-04 | @ KCA | 135 | L 3-6 | 70-65 | 3 | 12,462 | Matt Harrison | Jeremy Guthrie | Jeremy Guthrie | Matt Harrison | Greg Holland | 697 | 579 | 118 |
| 2012-09-05 | @ KCA | 136 | W 7-6 | 71-65 | 3 | 13,354 | Ryan Dempster | Everett Teaford | Ryan Dempster | Everett Teaford | Joe Nathan | 704 | 585 | 119 |
| 2012-09-06 | @ KCA | 137 | W 5-4 | 72-65 | 3 | 15,332 | Scott Feldman | Luke Hochevar | Mike Adams | Greg Holland | Joe Nathan | 709 | 589 | 120 |
| 2012-09-07 | @ TBA | 138 | L 1-3 | 72-66 | 3 | 19,545 | Derek Holland | Jeremy Hellickson | Wade Davis | Mark Lowe | | 710 | 592 | 118 |
| 2012-09-08 | @ TBA | 139 | W 4-2 | 73-66 | 3 | 18,702 | Yu Darvish | Chris Archer | Mike Adams | Kyle Farnsworth | Joe Nathan | 714 | 594 | 120 |
| 2012-09-09 | @ TBA | 140 | L 0-6 | 73-67 | 3 | 20,522 | Roy Oswalt | James Shields | James Shields | Roy Oswalt | | 714 | 600 | 114 |
| 2012-09-11 | vs CLE | 141 | W 6-4 | 74-67 | 3 | 34,765 | Matt Harrison | Ubaldo Jimenez | Matt Harrison | Ubaldo Jimenez | Joe Nathan | 720 | 604 | 116 |
| 2012-09-12 | vs CLE | 142 | W 5-2 | 75-67 | 3 | 36,001 | Ryan Dempster | Jeanmar Gomez | Ryan Dempster | Jeanmar Gomez | Joe Nathan | 725 | 606 | 119 |
| 2012-09-13 | vs CLE | 143 | L 4-5 | 75-68 | 3 | 36,102 | Derek Holland | Zach McAllister | Scott Maine | Joe Nathan | Chris Perez | 729 | 611 | 118 |
| 2012-09-14 | vs SEA | 144 | W 9-3 | 76-68 | 3 | 45,075 | Yu Darvish | Hisashi Iwakuma | Yu Darvish | Hisashi Iwakuma | | 738 | 614 | 124 |
| 2012-09-15 | vs SEA | 145 | L 6-8 | 76-69 | 3 | 47,267 | Scott Feldman | Jason Vargas | Lucas Luetge | Tanner Scheppers | Tom Wilhelmsen | 744 | 622 | 122 |
| 2012-09-16 | vs SEA | 146 | W 2-1 | 77-69 | 3 | 45,928 | Matt Harrison | Blake Beavan | Matt Harrison | Blake Beavan | Koji Uehara | 746 | 623 | 123 |
| 2012-09-18 | @ ANA | 147 | W 3-11 | 78-69 | 3 | 36,948 | Ryan Dempster | Jered Weaver | Jered Weaver | Ryan Dempster | | 749 | 634 | 115 |
| 2012-09-19 | @ ANA | 148 | W 6-2 | 79-69 | 3 | 37,093 | Derek Holland | C.J. Wilson | Derek Holland | C.J. Wilson | | 755 | 636 | 119 |
| 2012-09-20 | @ ANA | 149 | W 3-1 | 80-69 | 3 | 38,205 | Yu Darvish | Zack Greinke | Yu Darvish | Ernesto Frieri | Joe Nathan | 758 | 637 | 121 |
| 2012-09-21 | @ SEA | 150 | L 3-6 | 80-70 | 3 | 17,893 | Martin Perez | Hisashi Iwakuma | Hisashi Iwakuma | Martin Perez | Tom Wilhelmsen | 761 | 643 | 118 |
| 2012-09-22 | @ SEA | 151 | L 0-1 | 80-71 | 3 | 17,671 | Matt Harrison | Blake Beavan | Blake Beavan | Matt Harrison | Tom Wilhelmsen | 761 | 644 | 117 |
| 2012-09-23 | @ SEA | 152 | W 3-2 | 81-71 | 3 | 19,024 | Ryan Dempster | Jason Vargas | Ryan Dempster | Jason Vargas | Joe Nathan | 764 | 646 | 118 |
| 2012-09-24 | vs OAK | 153 | W 5-4 | 82-71 | 3 | 43,044 | Derek Holland | Dan Straily | Joe Nathan | Tyson Ross | | 769 | 650 | 119 |
| 2012-09-25 | vs OAK | 154 | L 2-3 | 82-72 | 3 | 43,874 | Scott Feldman | Tom Milone | Evan Scribner | Mark Lowe | Grant Balfour | 771 | 653 | 118 |
| 2012-09-26 | vs OAK | 155 | L 3-9 | 82-73 | 3 | 46,689 | Martin Perez | Jarrod Parker | Jarrod Parker | Martin Perez | | 774 | 662 | 112 |
| 2012-09-27 | vs OAK | 156 | W 9-7 | 83-73 | 3 | 43,796 | Matt Harrison | Travis Blackley | Matt Harrison | Travis Blackley | Joe Nathan | 783 | 669 | 114 |
| 2012-09-28 | vs ANA | 157 | L 4-7 | 83-74 | 3 | 46,662 | Ryan Dempster | Jered Weaver | Jered Weaver | Ryan Dempster | Ernesto Frieri | 787 | 676 | 111 |
| 2012-09-30 | vs ANA | 158 | L 4-5 | 83-75 | 5 | 46,713 | Yu Darvish | Zack Greinke | Garrett Richards | Joe Nathan | Ernesto Frieri | 791 | 681 | 110 |
| 2012-09-30 | vs ANA | 159 | W 8-7 | 83-75 | 5 | 48,089 | Derek Holland | Ervin Santana | Derek Holland | Ervin Santana | Joe Nathan | 799 | 688 | 111 |
| 2012-10-01 | @ OAK | 160 | L 3-4 | 84-76 | 3 | 21,162 | Martin Perez | Jarrod Parker | Jarrod Parker | Martin Perez | Grant Balfour | 802 | 692 | 110 |
| 2012-10-02 | @ OAK | 161 | L 1-3 | 84-77 | 3 | 30,660 | Matt Harrison | Travis Blackley | Travis Blackley | Matt Harrison | Grant Balfour | 803 | 695 | 108 |
| 2012-10-03 | @ OAK | 162 | W 5-12 | 85-77 | 3 | 36,067 | Ryan Dempster | A.J. Griffin | Evan Scribner | Derek Holland | | 808 | 707 | 101 |