| 2012-03-28 | @ OAK | 1 | W 3-1 | 1-0 | 1 | 44,227 | Felix Hernandez | Brandon McCarthy | Tom Wilhelmsen | Andrew Carignan | Brandon League | 3 | 1 | 2 |
| 2012-03-29 | @ OAK | 2 | L 1-4 | 1-1 | 2 | 43,391 | Jason Vargas | Bartolo Colon | Bartolo Colon | Shawn Kelley | Grant Balfour | 4 | 5 | -1 |
| 2012-04-06 | @ OAK | 3 | W 7-3 | 2-1 | 3 | 35,067 | Jason Vargas | Brandon McCarthy | Jason Vargas | Brandon McCarthy | | 11 | 8 | 3 |
| 2012-04-07 | @ OAK | 4 | W 8-7 | 3-1 | 1 | 16,612 | Felix Hernandez | Bartolo Colon | Felix Hernandez | Bartolo Colon | Brandon League | 19 | 15 | 4 |
| 2012-04-09 | @ TEX | 5 | W 5-11 | 4-1 | 1 | 42,003 | Hector Noesi | Yu Darvish | Yu Darvish | Hector Noesi | | 24 | 26 | -2 |
| 2012-04-10 | @ TEX | 6 | L 0-1 | 4-2 | 1 | 25,753 | Blake Beavan | Neftali Feliz | Neftali Feliz | Blake Beavan | Joe Nathan | 24 | 27 | -3 |
| 2012-04-11 | @ TEX | 7 | W 4-3 | 5-2 | 1 | 32,342 | Kevin Millwood | Colby Lewis | Lucas Luetge | Joe Nathan | Brandon League | 28 | 30 | -2 |
| 2012-04-12 | @ TEX | 8 | L 3-5 | 5-3 | 1 | 31,513 | Jason Vargas | Derek Holland | Derek Holland | Jason Vargas | Mike Adams | 31 | 35 | -4 |
| 2012-04-13 | vs OAK | 9 | L 0-4 | 5-4 | 2 | 46,026 | Felix Hernandez | Bartolo Colon | Bartolo Colon | Felix Hernandez | | 31 | 39 | -8 |
| 2012-04-14 | vs OAK | 10 | W 4-0 | 6-4 | 2 | 21,071 | Hector Noesi | Tom Milone | Hector Noesi | Tom Milone | | 35 | 39 | -4 |
| 2012-04-15 | vs OAK | 11 | W 5-3 | 7-4 | 2 | 19,650 | Blake Beavan | Graham Godfrey | Blake Beavan | Graham Godfrey | Brandon League | 40 | 42 | -2 |
| 2012-04-17 | vs CLE | 12 | L 8-9 | 7-5 | 2 | 12,461 | Kevin Millwood | Justin Masterson | Rafael Perez | Charlie Furbush | Chris Perez | 48 | 51 | -3 |
| 2012-04-18 | vs CLE | 13 | W 4-1 | 8-5 | 2 | 11,343 | Jason Vargas | Derek Lowe | Jason Vargas | Derek Lowe | Brandon League | 52 | 52 | 0 |
| 2012-04-19 | vs CLE | 14 | L 1-2 | 8-6 | 2 | 12,942 | Felix Hernandez | Josh Tomlin | Josh Tomlin | Brandon League | Chris Perez | 53 | 54 | -1 |
| 2012-04-20 | vs CHA | 15 | L 3-7 | 8-7 | 2 | 19,947 | Hector Noesi | Chris Sale | Chris Sale | Hector Noesi | | 56 | 61 | -5 |
| 2012-04-21 | vs CHA | 16 | L 0-4 | 8-8 | 4 | 22,472 | Blake Beavan | Philip Humber | Philip Humber | Blake Beavan | | 56 | 65 | -9 |
| 2012-04-22 | vs CHA | 17 | L 4-7 | 8-9 | 4 | 19,975 | Kevin Millwood | John Danks | John Danks | Kevin Millwood | Hector Santiago | 60 | 72 | -12 |
| 2012-04-24 | @ DET | 18 | W 7-4 | 9-9 | 2 | 30,073 | Jason Vargas | Max Scherzer | Jason Vargas | Max Scherzer | Brandon League | 67 | 76 | -9 |
| 2012-04-25 | @ DET | 19 | W 9-1 | 10-9 | 2 | 28,527 | Felix Hernandez | Adam Wilk | Felix Hernandez | Adam Wilk | | 76 | 77 | -1 |
| 2012-04-26 | @ DET | 20 | W 5-4 | 11-9 | 2 | 31,451 | Hector Noesi | Rick Porcello | Charlie Furbush | Rick Porcello | Brandon League | 81 | 81 | 0 |
| 2012-04-27 | @ TOR | 21 | W 9-5 | 12-9 | 1 | 24,303 | Blake Beavan | Ricky Romero | Charlie Furbush | Luis Perez | | 90 | 86 | 4 |
| 2012-04-28 | @ TOR | 22 | L 0-7 | 12-10 | 2 | 30,765 | Kevin Millwood | Brandon Morrow | Brandon Morrow | Kevin Millwood | | 90 | 93 | -3 |
| 2012-04-29 | @ TOR | 23 | L 2-7 | 12-11 | 2 | 22,320 | Jason Vargas | Henderson Alvarez | Henderson Alvarez | Jason Vargas | | 92 | 100 | -8 |
| 2012-04-30 | @ TBA | 24 | L 2-3 | 12-12 | 3 | 9,458 | Felix Hernandez | Jeremy Hellickson | J.P. Howell | Brandon League | | 94 | 103 | -9 |
| 2012-05-01 | @ TBA | 25 | L 1-3 | 12-13 | 3 | 9,972 | Hector Noesi | Matt Moore | Matt Moore | Hector Noesi | Fernando Rodney | 95 | 106 | -11 |
| 2012-05-02 | @ TBA | 26 | L 4-5 | 12-14 | 4 | 9,837 | Blake Beavan | James Shields | James Shields | Blake Beavan | Joel Peralta | 99 | 111 | -12 |
| 2012-05-03 | @ TBA | 27 | L 3-4 | 12-15 | 4 | 11,575 | Kevin Millwood | Jeff Niemann | Jeff Niemann | Kevin Millwood | Fernando Rodney | 102 | 115 | -13 |
| 2012-05-04 | vs MIN | 28 | L 2-3 | 12-16 | 4 | 22,492 | Jason Vargas | Carl Pavano | Carl Pavano | Tom Wilhelmsen | Matt Capps | 104 | 118 | -14 |
| 2012-05-05 | vs MIN | 29 | W 7-0 | 13-16 | 4 | 28,437 | Felix Hernandez | Jason Marquis | Felix Hernandez | Jason Marquis | | 111 | 118 | -7 |
| 2012-05-06 | vs MIN | 30 | W 5-2 | 14-16 | 4 | 23,913 | Hector Noesi | Nick Blackburn | Hector Noesi | Nick Blackburn | | 116 | 120 | -4 |
| 2012-05-07 | vs DET | 31 | W 3-2 | 15-16 | 4 | 14,462 | Blake Beavan | Doug Fister | Steve Delabar | Octavio Dotel | | 119 | 122 | -3 |
| 2012-05-08 | vs DET | 32 | L 4-6 | 15-17 | 4 | 13,455 | Kevin Millwood | Justin Verlander | Justin Verlander | Kevin Millwood | Jose Valverde | 123 | 128 | -5 |
| 2012-05-09 | vs DET | 33 | W 2-1 | 16-17 | 4 | 15,655 | Jason Vargas | Drew Smyly | Jason Vargas | Luke Putkonen | Brandon League | 125 | 129 | -4 |
| 2012-05-11 | @ NYA | 34 | L 2-6 | 16-18 | 4 | 37,226 | Felix Hernandez | Hiroki Kuroda | Hiroki Kuroda | Felix Hernandez | | 127 | 135 | -8 |
| 2012-05-12 | @ NYA | 35 | L 2-6 | 16-19 | 4 | 43,954 | Hector Noesi | Phil Hughes | Phil Hughes | Hector Noesi | Boone Logan | 129 | 141 | -12 |
| 2012-05-13 | @ NYA | 36 | W 6-2 | 17-19 | 3 | 41,631 | Kevin Millwood | Andy Pettitte | Kevin Millwood | Andy Pettitte | | 135 | 143 | -8 |
| 2012-05-14 | @ BOS | 37 | L 1-6 | 17-20 | 3 | 37,334 | Jason Vargas | Jon Lester | Jon Lester | Jason Vargas | | 136 | 149 | -13 |
| 2012-05-15 | @ BOS | 38 | L 0-5 | 17-21 | 3 | 37,292 | Blake Beavan | Josh Beckett | Josh Beckett | Blake Beavan | | 136 | 154 | -18 |
| 2012-05-16 | @ CLE | 39 | L 3-9 | 17-22 | 4 | 12,092 | Felix Hernandez | Ubaldo Jimenez | Ubaldo Jimenez | Felix Hernandez | | 139 | 163 | -24 |
| 2012-05-17 | @ CLE | 40 | L 5-6 | 17-23 | 4 | 12,894 | Hector Noesi | Zach McAllister | Joe Smith | Brandon League | | 144 | 169 | -25 |
| 2012-05-18 | @ COL | 41 | W 4-0 | 18-23 | 4 | 34,887 | Kevin Millwood | Alex White | Kevin Millwood | Alex White | | 148 | 169 | -21 |
| 2012-05-19 | @ COL | 42 | L 10-3 | 18-24 | 4 | 30,784 | Jason Vargas | Christian Friedrich | Jason Vargas | Christian Friedrich | | 158 | 172 | -14 |
| 2012-05-20 | @ COL | 43 | W 6-4 | 19-24 | 4 | 36,662 | Blake Beavan | Jeremy Guthrie | Blake Beavan | Jeremy Guthrie | | 164 | 176 | -12 |
| 2012-05-21 | vs TEX | 44 | W 6-1 | 20-24 | 3 | 18,672 | Felix Hernandez | Yu Darvish | Felix Hernandez | Yu Darvish | | 170 | 177 | -7 |
| 2012-05-22 | vs TEX | 45 | L 1-3 | 20-25 | 4 | 15,604 | Hector Noesi | Matt Harrison | Matt Harrison | Hector Noesi | Joe Nathan | 171 | 180 | -9 |
| 2012-05-23 | vs TEX | 46 | W 5-3 | 21-25 | 3 | 23,097 | Kevin Millwood | Scott Feldman | Kevin Millwood | Scott Feldman | Brandon League | 176 | 183 | -7 |
| 2012-05-24 | vs ANA | 47 | L 0-3 | 21-26 | 3 | 18,048 | Jason Vargas | Dan Haren | Dan Haren | Jason Vargas | | 176 | 186 | -10 |
| 2012-05-25 | vs ANA | 48 | L 4-6 | 21-27 | 3 | 23,517 | Blake Beavan | Ervin Santana | Jason Isringhausen | Brandon League | Scott Downs | 180 | 192 | -12 |
| 2012-05-26 | vs ANA | 49 | L 3-5 | 21-28 | 4 | 29,483 | Felix Hernandez | Jerome Williams | Jerome Williams | Felix Hernandez | Ernesto Frieri | 183 | 197 | -14 |
| 2012-05-27 | vs ANA | 50 | L 2-4 | 21-29 | 4 | 24,467 | Hector Noesi | C.J. Wilson | C.J. Wilson | Hector Noesi | Scott Downs | 185 | 201 | -16 |
| 2012-05-28 | @ TEX | 51 | L 2-4 | 21-30 | 4 | 41,384 | Kevin Millwood | Matt Harrison | Matt Harrison | Steve Delabar | Joe Nathan | 187 | 205 | -18 |
| 2012-05-29 | @ TEX | 52 | L 10-3 | 21-31 | 4 | 34,531 | Jason Vargas | Scott Feldman | Jason Vargas | Scott Feldman | | 197 | 208 | -11 |
| 2012-05-30 | @ TEX | 53 | L 21-8 | 21-32 | 4 | 43,580 | Blake Beavan | Derek Holland | Blake Beavan | Derek Holland | Hisashi Iwakuma | 218 | 216 | 2 |
| 2012-06-01 | @ CHA | 54 | L 4-7 | 21-33 | 4 | 19,168 | Felix Hernandez | Jake Peavy | Jesse Crain | Shawn Kelley | Addison Reed | 222 | 223 | -1 |
| 2012-06-02 | @ CHA | 55 | L 10-8 | 21-34 | 4 | 26,200 | Hector Noesi | Gavin Floyd | Tom Wilhelmsen | Addison Reed | Hisashi Iwakuma | 232 | 231 | 1 |
| 2012-06-03 | @ CHA | 56 | L 2-4 | 21-35 | 4 | 23,062 | Kevin Millwood | Chris Sale | Chris Sale | Kevin Millwood | | 234 | 235 | -1 |
| 2012-06-04 | @ ANA | 57 | W 8-6 | 22-35 | 4 | 36,079 | Jason Vargas | Ervin Santana | Jason Vargas | Ervin Santana | Tom Wilhelmsen | 242 | 241 | 1 |
| 2012-06-05 | @ ANA | 58 | L 1-6 | 22-36 | 4 | 35,021 | Blake Beavan | Garrett Richards | Garrett Richards | Blake Beavan | | 243 | 247 | -4 |
| 2012-06-06 | @ ANA | 59 | W 8-6 | 23-36 | 4 | 37,342 | Hector Noesi | Jerome Williams | Shawn Kelley | Jerome Williams | Tom Wilhelmsen | 251 | 253 | -2 |
| 2012-06-08 | vs LAN | 60 | W 1-0 | 24-36 | 4 | 22,028 | Kevin Millwood | Nathan Eovaldi | Stephen Pryor | Scott Elbert | Tom Wilhelmsen | 252 | 253 | -1 |
| 2012-06-09 | vs LAN | 61 | L 3-8 | 24-37 | 4 | 30,287 | Jason Vargas | Clayton Kershaw | Clayton Kershaw | Jason Vargas | | 255 | 261 | -6 |
| 2012-06-10 | vs LAN | 62 | L 2-8 | 24-38 | 4 | 34,807 | Blake Beavan | Chad Billingsley | Chad Billingsley | Blake Beavan | | 257 | 269 | -12 |
| 2012-06-12 | vs SDN | 63 | L 4-5 | 24-39 | 4 | 13,084 | Felix Hernandez | Clayton Richard | Clayton Richard | Felix Hernandez | Huston Street | 261 | 274 | -13 |
| 2012-06-13 | vs SDN | 64 | L 0-1 | 24-40 | 4 | 13,931 | Hector Noesi | Jason Marquis | Jason Marquis | Hector Noesi | Huston Street | 261 | 275 | -14 |
| 2012-06-14 | vs SDN | 65 | L 2-6 | 24-41 | 4 | 17,306 | Erasmo Ramirez | Edinson Volquez | Edinson Volquez | Erasmo Ramirez | | 263 | 281 | -18 |
| 2012-06-15 | vs SFN | 66 | L 2-4 | 24-42 | 4 | 29,818 | Jason Vargas | Ryan Vogelsong | Ryan Vogelsong | Jason Vargas | Santiago Casilla | 265 | 285 | -20 |
| 2012-06-16 | vs SFN | 67 | W 7-4 | 25-42 | 4 | 30,589 | Kevin Millwood | Tim Lincecum | Hisashi Iwakuma | Tim Lincecum | Tom Wilhelmsen | 272 | 289 | -17 |
| 2012-06-17 | vs SFN | 68 | W 2-1 | 26-42 | 4 | 40,603 | Felix Hernandez | Madison Bumgarner | Tom Wilhelmsen | Sergio Romo | | 274 | 290 | -16 |
| 2012-06-18 | @ ARI | 69 | L 1-7 | 26-43 | 4 | 24,284 | Hector Noesi | Wade Miley | Wade Miley | Hector Noesi | | 275 | 297 | -22 |
| 2012-06-19 | @ ARI | 70 | L 12-9 | 26-44 | 4 | 21,568 | Erasmo Ramirez | Daniel Hudson | Charlie Furbush | J.J. Putz | Tom Wilhelmsen | 287 | 306 | -19 |
| 2012-06-20 | @ ARI | 71 | L 10-14 | 26-45 | 4 | 29,630 | Jason Vargas | Trevor Cahill | Trevor Cahill | Jason Vargas | | 297 | 320 | -23 |
| 2012-06-22 | @ SDN | 72 | L 5-9 | 26-46 | 4 | 30,053 | Kevin Millwood | Clayton Richard | Clayton Richard | Kevin Millwood | Huston Street | 302 | 329 | -27 |
| 2012-06-23 | @ SDN | 73 | W 5-1 | 27-46 | 4 | 30,922 | Felix Hernandez | Jason Marquis | Felix Hernandez | Jason Marquis | | 307 | 330 | -23 |
| 2012-06-24 | @ SDN | 74 | L 0-2 | 27-47 | 4 | 27,529 | Hector Noesi | Edinson Volquez | Edinson Volquez | Hector Noesi | Huston Street | 307 | 332 | -25 |
| 2012-06-25 | vs OAK | 75 | L 0-1 | 27-48 | 4 | 17,101 | Erasmo Ramirez | Tom Milone | Tom Milone | Erasmo Ramirez | Ryan Cook | 307 | 333 | -26 |
| 2012-06-26 | vs OAK | 76 | W 3-2 | 28-48 | 4 | 12,411 | Jason Vargas | Travis Blackley | Charlie Furbush | Jim Miller | Tom Wilhelmsen | 310 | 335 | -25 |
| 2012-06-27 | vs OAK | 77 | L 1-2 | 28-49 | 4 | 18,158 | Kevin Millwood | Jarrod Parker | Jarrod Parker | Hisashi Iwakuma | Ryan Cook | 311 | 337 | -26 |
| 2012-06-28 | vs BOS | 78 | W 1-0 | 29-49 | 4 | 20,692 | Felix Hernandez | Franklin Morales | Felix Hernandez | Scott Atchison | | 312 | 337 | -25 |
| 2012-06-29 | vs BOS | 79 | L 0-5 | 29-50 | 4 | 23,094 | Hector Noesi | Aaron Cook | Aaron Cook | Hector Noesi | | 312 | 342 | -30 |
| 2012-06-30 | vs BOS | 80 | W 3-2 | 30-50 | 4 | 31,311 | Erasmo Ramirez | Josh Beckett | Shawn Kelley | Alfredo Aceves | | 315 | 344 | -29 |
| 2012-07-01 | vs BOS | 81 | L 1-2 | 30-51 | 4 | 34,065 | Jason Vargas | Felix Doubront | Vicente Padilla | Brandon League | Alfredo Aceves | 316 | 346 | -30 |
| 2012-07-02 | vs BAL | 82 | W 6-3 | 31-51 | 4 | 14,805 | Hisashi Iwakuma | Jason Hammel | Steve Delabar | Jason Hammel | Tom Wilhelmsen | 322 | 349 | -27 |
| 2012-07-03 | vs BAL | 83 | L 4-5 | 31-52 | 4 | 16,270 | Felix Hernandez | Wei-Yin Chen | Darren O'Day | Charlie Furbush | Jim Johnson | 326 | 354 | -28 |
| 2012-07-04 | vs BAL | 84 | L 2-4 | 31-53 | 4 | 21,982 | Hector Noesi | Chris Tillman | Chris Tillman | Hector Noesi | Jim Johnson | 328 | 358 | -30 |
| 2012-07-06 | @ OAK | 85 | L 1-4 | 31-54 | 4 | 10,819 | Kevin Millwood | Tom Milone | Jordan Norberto | Oliver Perez | | 329 | 362 | -33 |
| 2012-07-07 | @ OAK | 86 | W 7-1 | 32-54 | 4 | 16,136 | Jason Vargas | Jarrod Parker | Jason Vargas | Jarrod Parker | | 336 | 363 | -27 |
| 2012-07-08 | @ OAK | 87 | L 1-2 | 32-55 | 4 | 20,075 | Felix Hernandez | Bartolo Colon | Jordan Norberto | Oliver Perez | | 337 | 365 | -28 |
| 2012-07-13 | vs TEX | 88 | L 2-3 | 32-56 | 4 | 23,721 | Kevin Millwood | Derek Holland | Derek Holland | Kevin Millwood | Joe Nathan | 339 | 368 | -29 |
| 2012-07-14 | vs TEX | 89 | W 7-0 | 33-56 | 4 | 29,951 | Felix Hernandez | Yu Darvish | Felix Hernandez | Yu Darvish | | 346 | 368 | -22 |
| 2012-07-15 | vs TEX | 90 | L 0-4 | 33-57 | 4 | 27,378 | Hisashi Iwakuma | Matt Harrison | Matt Harrison | Hisashi Iwakuma | | 346 | 372 | -26 |
| 2012-07-16 | @ KCA | 91 | W 9-4 | 34-57 | 4 | 16,697 | Jason Vargas | Jonathan Sanchez | Jason Vargas | Jonathan Sanchez | | 355 | 376 | -21 |
| 2012-07-17 | @ KCA | 92 | W 9-6 | 35-57 | 4 | 15,769 | Blake Beavan | Ryan Verdugo | Blake Beavan | Ryan Verdugo | Tom Wilhelmsen | 364 | 382 | -18 |
| 2012-07-18 | @ KCA | 93 | L 7-8 | 35-58 | 4 | 17,312 | Kevin Millwood | Bruce Chen | Greg Holland | Josh Kinney | | 371 | 390 | -19 |
| 2012-07-19 | @ KCA | 94 | W 6-1 | 36-58 | 4 | 16,706 | Felix Hernandez | Will Smith | Felix Hernandez | Will Smith | | 377 | 391 | -14 |
| 2012-07-20 | @ TBA | 95 | L 3-4 | 36-59 | 4 | 14,143 | Hisashi Iwakuma | James Shields | Jake McGee | Tom Wilhelmsen | | 380 | 395 | -15 |
| 2012-07-21 | @ TBA | 96 | W 2-1 | 37-59 | 4 | 18,800 | Jason Vargas | Alex Cobb | Jason Vargas | Alex Cobb | Tom Wilhelmsen | 382 | 396 | -14 |
| 2012-07-22 | @ TBA | 97 | W 2-1 | 38-59 | 4 | 20,908 | Blake Beavan | Matt Moore | Blake Beavan | Matt Moore | Tom Wilhelmsen | 384 | 397 | -13 |
| 2012-07-23 | vs NYA | 98 | L 1-4 | 38-60 | 4 | 29,911 | Kevin Millwood | Hiroki Kuroda | Hiroki Kuroda | Kevin Millwood | Rafael Soriano | 385 | 401 | -16 |
| 2012-07-24 | vs NYA | 99 | W 4-2 | 39-60 | 4 | 31,908 | Felix Hernandez | Freddy Garcia | Felix Hernandez | Freddy Garcia | Tom Wilhelmsen | 389 | 403 | -14 |
| 2012-07-25 | vs NYA | 100 | L 2-5 | 39-61 | 4 | 36,071 | Hisashi Iwakuma | Ivan Nova | David Phelps | Lucas Luetge | Rafael Soriano | 391 | 408 | -17 |
| 2012-07-26 | vs KCA | 101 | W 4-1 | 40-61 | 4 | 15,014 | Jason Vargas | Luis Mendoza | Jason Vargas | Luis Mendoza | Tom Wilhelmsen | 395 | 409 | -14 |
| 2012-07-27 | vs KCA | 102 | W 6-1 | 41-61 | 4 | 14,953 | Blake Beavan | Jeremy Guthrie | Blake Beavan | Jeremy Guthrie | | 401 | 410 | -9 |
| 2012-07-28 | vs KCA | 103 | W 4-3 | 42-61 | 4 | 32,111 | Kevin Millwood | Bruce Chen | Kevin Millwood | Bruce Chen | Tom Wilhelmsen | 405 | 413 | -8 |
| 2012-07-29 | vs KCA | 104 | W 7-6 | 43-61 | 4 | 19,402 | Felix Hernandez | Will Smith | Oliver Perez | Jose Mijares | Tom Wilhelmsen | 412 | 419 | -7 |
| 2012-07-30 | vs TOR | 105 | W 4-1 | 44-61 | 4 | 22,443 | Hisashi Iwakuma | Ricky Romero | Hisashi Iwakuma | Ricky Romero | Lucas Luetge | 416 | 420 | -4 |
| 2012-07-31 | vs TOR | 106 | W 7-2 | 45-61 | 4 | 21,434 | Jason Vargas | Aaron Laffey | Jason Vargas | Aaron Laffey | | 423 | 422 | 1 |
| 2012-08-01 | vs TOR | 107 | W 5-3 | 46-61 | 4 | 22,537 | Blake Beavan | Carlos Villanueva | Blake Beavan | Carlos Villanueva | Tom Wilhelmsen | 428 | 425 | 3 |
| 2012-08-03 | @ NYA | 108 | L 3-6 | 46-62 | 4 | 45,872 | Kevin Millwood | CC Sabathia | CC Sabathia | Kevin Millwood | | 431 | 431 | 0 |
| 2012-08-04 | @ NYA | 109 | W 1-0 | 47-62 | 4 | 47,067 | Felix Hernandez | Hiroki Kuroda | Felix Hernandez | Hiroki Kuroda | | 432 | 431 | 1 |
| 2012-08-05 | @ NYA | 110 | L 2-6 | 47-63 | 4 | 45,878 | Hisashi Iwakuma | Freddy Garcia | Freddy Garcia | Hisashi Iwakuma | | 434 | 437 | -3 |
| 2012-08-06 | @ BAL | 111 | L 1-3 | 47-64 | 4 | 21,184 | Jason Vargas | Chris Tillman | Chris Tillman | Jason Vargas | Jim Johnson | 435 | 440 | -5 |
| 2012-08-07 | @ BAL | 112 | L 7-8 | 47-65 | 4 | 15,433 | Blake Beavan | Zachary Britton | Darren O'Day | Shawn Kelley | | 442 | 448 | -6 |
| 2012-08-08 | @ BAL | 113 | L 2-9 | 47-66 | 4 | 17,312 | Kevin Millwood | Steve Johnson | Steve Johnson | Kevin Millwood | | 444 | 457 | -13 |
| 2012-08-10 | @ ANA | 114 | L 5-6 | 47-67 | 4 | 39,016 | Felix Hernandez | Ervin Santana | Ernesto Frieri | Josh Kinney | | 449 | 463 | -14 |
| 2012-08-11 | @ ANA | 115 | W 7-4 | 48-67 | 4 | 38,722 | Hisashi Iwakuma | Dan Haren | Hisashi Iwakuma | Dan Haren | | 456 | 467 | -11 |
| 2012-08-12 | @ ANA | 116 | W 4-1 | 49-67 | 4 | 36,505 | Jason Vargas | Jered Weaver | Jason Vargas | Jered Weaver | Tom Wilhelmsen | 460 | 468 | -8 |
| 2012-08-13 | vs TBA | 117 | L 1-4 | 49-68 | 4 | 16,205 | Blake Beavan | Alex Cobb | Alex Cobb | Blake Beavan | Fernando Rodney | 461 | 472 | -11 |
| 2012-08-14 | vs TBA | 118 | W 3-2 | 50-68 | 4 | 17,065 | Kevin Millwood | Matt Moore | Stephen Pryor | Fernando Rodney | | 464 | 474 | -10 |
| 2012-08-15 | vs TBA | 119 | W 1-0 | 51-68 | 4 | 21,889 | Felix Hernandez | Jeremy Hellickson | Felix Hernandez | Jeremy Hellickson | | 465 | 474 | -9 |
| 2012-08-17 | vs MIN | 120 | W 5-3 | 52-68 | 4 | 22,602 | Hisashi Iwakuma | Nick Blackburn | Hisashi Iwakuma | Nick Blackburn | Tom Wilhelmsen | 470 | 477 | -7 |
| 2012-08-18 | vs MIN | 121 | W 3-2 | 53-68 | 4 | 21,154 | Jason Vargas | Scott Diamond | Tom Wilhelmsen | Tyler Robertson | | 473 | 479 | -6 |
| 2012-08-19 | vs MIN | 122 | W 5-1 | 54-68 | 4 | 22,635 | Blake Beavan | Samuel Deduno | Blake Beavan | Samuel Deduno | Josh Kinney | 478 | 480 | -2 |
| 2012-08-20 | vs CLE | 123 | W 5-3 | 55-68 | 4 | 14,687 | Kevin Millwood | Ubaldo Jimenez | Charlie Furbush | Joe Smith | Tom Wilhelmsen | 483 | 483 | 0 |
| 2012-08-21 | vs CLE | 124 | W 5-1 | 56-68 | 4 | 39,204 | Felix Hernandez | Fausto Carmona | Felix Hernandez | Fausto Carmona | Lucas Luetge | 488 | 484 | 4 |
| 2012-08-22 | vs CLE | 125 | W 3-1 | 57-68 | 4 | 18,578 | Hisashi Iwakuma | Zach McAllister | Stephen Pryor | Vinnie Pestano | Tom Wilhelmsen | 491 | 485 | 6 |
| 2012-08-24 | @ CHA | 126 | L 8-9 | 57-69 | 4 | 25,058 | Jason Vargas | Jake Peavy | Addison Reed | Tom Wilhelmsen | | 499 | 494 | 5 |
| 2012-08-25 | @ CHA | 127 | L 4-5 | 57-70 | 4 | 27,562 | Blake Beavan | Jose Quintana | Nate Jones | Blake Beavan | Addison Reed | 503 | 499 | 4 |
| 2012-08-26 | @ CHA | 128 | L 3-4 | 57-71 | 4 | 23,146 | Kevin Millwood | Gavin Floyd | Nate Jones | Kevin Millwood | | 506 | 503 | 3 |
| 2012-08-27 | @ MIN | 129 | W 1-0 | 58-71 | 4 | 31,883 | Felix Hernandez | Liam Hendriks | Felix Hernandez | Liam Hendriks | | 507 | 503 | 4 |
| 2012-08-28 | @ MIN | 130 | W 5-2 | 59-71 | 4 | 29,854 | Hisashi Iwakuma | Scott Diamond | Hisashi Iwakuma | Scott Diamond | Tom Wilhelmsen | 512 | 505 | 7 |
| 2012-08-29 | @ MIN | 131 | L 0-10 | 59-72 | 4 | 29,281 | Jason Vargas | Samuel Deduno | Samuel Deduno | Jason Vargas | | 512 | 515 | -3 |
| 2012-08-30 | @ MIN | 132 | W 5-4 | 60-72 | 4 | 32,578 | Blake Beavan | Brian Duensing | Blake Beavan | Brian Duensing | Tom Wilhelmsen | 517 | 519 | -2 |
| 2012-08-31 | vs ANA | 133 | L 1-9 | 60-73 | 4 | 17,739 | Kevin Millwood | Dan Haren | Dan Haren | Kevin Millwood | | 518 | 528 | -10 |
| 2012-09-01 | vs ANA | 134 | L 2-5 | 60-74 | 4 | 22,910 | Felix Hernandez | Ervin Santana | Ervin Santana | Felix Hernandez | Ernesto Frieri | 520 | 533 | -13 |
| 2012-09-02 | vs ANA | 135 | W 2-1 | 61-74 | 4 | 20,584 | Hisashi Iwakuma | Jered Weaver | Hisashi Iwakuma | Jered Weaver | Tom Wilhelmsen | 522 | 534 | -12 |
| 2012-09-03 | vs BOS | 136 | W 4-1 | 62-74 | 4 | 21,641 | Jason Vargas | Clay Buchholz | Jason Vargas | Clay Buchholz | Tom Wilhelmsen | 526 | 535 | -9 |
| 2012-09-04 | vs BOS | 137 | L 3-4 | 62-75 | 4 | 12,754 | Blake Beavan | Jon Lester | Jon Lester | Blake Beavan | Andrew Bailey | 529 | 539 | -10 |
| 2012-09-05 | vs BOS | 138 | W 2-1 | 63-75 | 4 | 13,037 | Kevin Millwood | Aaron Cook | Kevin Millwood | Aaron Cook | Tom Wilhelmsen | 531 | 540 | -9 |
| 2012-09-07 | vs OAK | 139 | L 1-6 | 63-76 | 4 | 17,128 | Felix Hernandez | A.J. Griffin | A.J. Griffin | Felix Hernandez | | 532 | 546 | -14 |
| 2012-09-08 | vs OAK | 140 | L 1-6 | 63-77 | 4 | 23,177 | Hisashi Iwakuma | Brett Anderson | Brett Anderson | Hisashi Iwakuma | | 533 | 552 | -19 |
| 2012-09-09 | vs OAK | 141 | L 2-4 | 63-78 | 4 | 14,403 | Jason Vargas | Tom Milone | Tom Milone | Jason Vargas | Grant Balfour | 535 | 556 | -21 |
| 2012-09-11 | @ TOR | 142 | W 4-3 | 64-78 | 4 | 12,935 | Erasmo Ramirez | Brandon Morrow | Erasmo Ramirez | Brandon Morrow | Tom Wilhelmsen | 539 | 559 | -20 |
| 2012-09-12 | @ TOR | 143 | W 3-2 | 65-78 | 4 | 13,519 | Kevin Millwood | Ricky Romero | Kevin Millwood | Ricky Romero | Tom Wilhelmsen | 542 | 561 | -19 |
| 2012-09-13 | @ TOR | 144 | L 3-8 | 65-79 | 4 | 13,756 | Felix Hernandez | Henderson Alvarez | Henderson Alvarez | Felix Hernandez | | 545 | 569 | -24 |
| 2012-09-14 | @ TEX | 145 | L 3-9 | 65-80 | 4 | 45,075 | Hisashi Iwakuma | Yu Darvish | Yu Darvish | Hisashi Iwakuma | | 548 | 578 | -30 |
| 2012-09-15 | @ TEX | 146 | W 8-6 | 66-80 | 4 | 47,267 | Jason Vargas | Scott Feldman | Lucas Luetge | Tanner Scheppers | Tom Wilhelmsen | 556 | 584 | -28 |
| 2012-09-16 | @ TEX | 147 | L 1-2 | 66-81 | 4 | 45,928 | Blake Beavan | Matt Harrison | Matt Harrison | Blake Beavan | Koji Uehara | 557 | 586 | -29 |
| 2012-09-17 | vs BAL | 148 | W 4-10 | 67-81 | 4 | 13,036 | Hector Noesi | Chris Tillman | Chris Tillman | Hector Noesi | | 561 | 596 | -35 |
| 2012-09-18 | vs BAL | 149 | L 2-4 | 67-82 | 4 | 12,608 | Erasmo Ramirez | Wei-Yin Chen | Tommy Hunter | Lucas Luetge | Jim Johnson | 563 | 600 | -37 |
| 2012-09-19 | vs BAL | 150 | L 1-3 | 67-83 | 4 | 14,001 | Felix Hernandez | Joe Saunders | Luis Ayala | Josh Kinney | Jim Johnson | 564 | 603 | -39 |
| 2012-09-21 | vs TEX | 151 | W 6-3 | 68-83 | 4 | 17,893 | Hisashi Iwakuma | Martin Perez | Hisashi Iwakuma | Martin Perez | Tom Wilhelmsen | 570 | 606 | -36 |
| 2012-09-22 | vs TEX | 152 | W 1-0 | 69-83 | 4 | 17,671 | Blake Beavan | Matt Harrison | Blake Beavan | Matt Harrison | Tom Wilhelmsen | 571 | 606 | -35 |
| 2012-09-23 | vs TEX | 153 | L 2-3 | 69-84 | 4 | 19,024 | Jason Vargas | Ryan Dempster | Ryan Dempster | Jason Vargas | Joe Nathan | 573 | 609 | -36 |
| 2012-09-25 | @ ANA | 154 | L 4-5 | 69-85 | 4 | 38,538 | Erasmo Ramirez | Zack Greinke | Zack Greinke | Erasmo Ramirez | Ernesto Frieri | 577 | 614 | -37 |
| 2012-09-26 | @ ANA | 155 | L 3-4 | 69-86 | 4 | 37,916 | Felix Hernandez | C.J. Wilson | Ernesto Frieri | Stephen Pryor | | 580 | 618 | -38 |
| 2012-09-27 | @ ANA | 156 | W 9-4 | 70-86 | 4 | 37,377 | Hisashi Iwakuma | Dan Haren | Hisashi Iwakuma | Dan Haren | | 589 | 622 | -33 |
| 2012-09-28 | @ OAK | 157 | L 2-8 | 70-87 | 4 | 16,376 | Blake Beavan | A.J. Griffin | A.J. Griffin | Blake Beavan | | 591 | 630 | -39 |
| 2012-09-29 | @ OAK | 158 | L 4-7 | 70-88 | 4 | 21,517 | Jason Vargas | Dan Straily | Grant Balfour | Oliver Perez | | 595 | 637 | -42 |
| 2012-09-30 | @ OAK | 159 | L 2-5 | 70-89 | 6 | 21,057 | Erasmo Ramirez | Tom Milone | Sean Doolittle | Shawn Kelley | Grant Balfour | 597 | 642 | -45 |
| 2012-10-01 | vs ANA | 160 | L 4-8 | 70-90 | 4 | 13,963 | Felix Hernandez | C.J. Wilson | C.J. Wilson | Felix Hernandez | | 601 | 650 | -49 |
| 2012-10-02 | vs ANA | 161 | W 6-1 | 71-90 | 4 | 14,353 | Hisashi Iwakuma | Dan Haren | Hisashi Iwakuma | Dan Haren | | 607 | 651 | -44 |
| 2012-10-03 | vs ANA | 162 | W 12-0 | 72-90 | 4 | 15,614 | Blake Beavan | Jered Weaver | Blake Beavan | Jered Weaver | | 619 | 651 | -32 |