| 2012-04-05 | vs TOR | 1 | L 4-7 | 0-1 | 2 | 43,190 | Justin Masterson | Ricky Romero | Luis Perez | Luis Valdez | | 4 | 7 | -3 |
| 2012-04-07 | vs TOR | 2 | L 4-7 | 0-2 | 4 | 18,842 | Ubaldo Jimenez | Brandon Morrow | Casey Janssen | Tony Sipp | | 8 | 14 | -6 |
| 2012-04-08 | vs TOR | 3 | W 4-3 | 1-2 | 4 | 10,518 | Derek Lowe | Joel Carreno | Derek Lowe | Joel Carreno | Chris Perez | 12 | 17 | -5 |
| 2012-04-09 | vs CHA | 4 | L 2-4 | 1-3 | 4 | 9,473 | Josh Tomlin | Chris Sale | Chris Sale | Josh Tomlin | Hector Santiago | 14 | 21 | -7 |
| 2012-04-11 | vs CHA | 5 | W 6-10 | 2-3 | 4 | 9,072 | Justin Masterson | John Danks | John Danks | Justin Masterson | | 20 | 31 | -11 |
| 2012-04-13 | @ KCA | 6 | W 8-3 | 3-3 | 3 | 40,230 | Derek Lowe | Luke Hochevar | Derek Lowe | Luke Hochevar | | 28 | 34 | -6 |
| 2012-04-14 | @ KCA | 7 | L 11-9 | 3-4 | 4 | 21,788 | Jeanmar Gomez | Jonathan Sanchez | Luis Valdez | Greg Holland | Chris Perez | 39 | 43 | -4 |
| 2012-04-15 | @ KCA | 8 | L 13-7 | 3-5 | 4 | 21,182 | Ubaldo Jimenez | Luis Mendoza | Ubaldo Jimenez | Luis Mendoza | | 52 | 50 | 2 |
| 2012-04-17 | @ SEA | 9 | W 9-8 | 4-5 | 4 | 12,461 | Justin Masterson | Kevin Millwood | Rafael Perez | Charlie Furbush | Chris Perez | 61 | 58 | 3 |
| 2012-04-18 | @ SEA | 10 | L 1-4 | 4-6 | 4 | 11,343 | Derek Lowe | Jason Vargas | Jason Vargas | Derek Lowe | Brandon League | 62 | 62 | 0 |
| 2012-04-19 | @ SEA | 11 | W 2-1 | 5-6 | 3 | 12,942 | Josh Tomlin | Felix Hernandez | Josh Tomlin | Brandon League | Chris Perez | 64 | 63 | 1 |
| 2012-04-20 | @ OAK | 12 | W 4-3 | 6-6 | 3 | 14,340 | Ubaldo Jimenez | Graham Godfrey | Ubaldo Jimenez | Graham Godfrey | Chris Perez | 68 | 66 | 2 |
| 2012-04-21 | @ OAK | 13 | W 5-1 | 7-6 | 4 | 25,258 | Jeanmar Gomez | Brandon McCarthy | Jeanmar Gomez | Brandon McCarthy | Chris Perez | 73 | 67 | 6 |
| 2012-04-22 | @ OAK | 14 | L 1-5 | 7-7 | 3 | 24,049 | Justin Masterson | Tyson Ross | Tyson Ross | Justin Masterson | | 74 | 72 | 2 |
| 2012-04-24 | vs KCA | 15 | W 4-3 | 8-7 | 3 | 9,137 | Derek Lowe | Jonathan Sanchez | Derek Lowe | Jonathan Sanchez | Chris Perez | 78 | 75 | 3 |
| 2012-04-25 | vs KCA | 16 | L 2-8 | 8-8 | 3 | 10,552 | Ubaldo Jimenez | Luke Hochevar | Luke Hochevar | Ubaldo Jimenez | | 80 | 83 | -3 |
| 2012-04-26 | vs KCA | 17 | L 2-4 | 8-9 | 3 | 9,229 | Josh Tomlin | Luis Mendoza | Luis Mendoza | Josh Tomlin | Jonathan Broxton | 82 | 87 | -5 |
| 2012-04-27 | vs ANA | 18 | W 3-2 | 9-9 | 3 | 12,597 | Justin Masterson | Jered Weaver | Vinnie Pestano | David Carpenter | | 85 | 89 | -4 |
| 2012-04-28 | vs ANA | 19 | L 1-2 | 9-10 | 3 | 11,316 | Jeanmar Gomez | Dan Haren | Dan Haren | Jeanmar Gomez | Scott Downs | 86 | 91 | -5 |
| 2012-04-29 | vs ANA | 20 | W 4-0 | 10-10 | 3 | 15,421 | Derek Lowe | Ervin Santana | Derek Lowe | Ervin Santana | | 90 | 91 | -1 |
| 2012-05-01 | @ CHA | 21 | L 2-7 | 10-11 | 3 | 15,212 | Ubaldo Jimenez | Chris Sale | Chris Sale | Ubaldo Jimenez | | 92 | 98 | -6 |
| 2012-05-02 | @ CHA | 22 | W 6-3 | 11-11 | 3 | 15,192 | Josh Tomlin | Philip Humber | Joe Smith | Will Ohman | Chris Perez | 98 | 101 | -3 |
| 2012-05-03 | @ CHA | 23 | W 7-5 | 12-11 | 3 | 17,314 | Justin Masterson | John Danks | Justin Masterson | John Danks | Chris Perez | 105 | 106 | -1 |
| 2012-05-04 | vs TEX | 24 | W 6-3 | 13-11 | 2 | 16,147 | Jeanmar Gomez | Colby Lewis | Jeanmar Gomez | Colby Lewis | Chris Perez | 111 | 109 | 2 |
| 2012-05-05 | vs TEX | 25 | L 2-5 | 13-12 | 3 | 21,307 | Derek Lowe | Derek Holland | Alexi Ogando | Joe Smith | Joe Nathan | 113 | 114 | -1 |
| 2012-05-06 | vs TEX | 26 | W 4-2 | 14-12 | 2 | 18,171 | Ubaldo Jimenez | Yu Darvish | Ubaldo Jimenez | Yu Darvish | Chris Perez | 117 | 116 | 1 |
| 2012-05-07 | vs CHA | 27 | W 8-6 | 15-12 | 3 | 9,196 | Zach McAllister | Philip Humber | Zach McAllister | Philip Humber | Nick Hagadone | 125 | 122 | 3 |
| 2012-05-07 | vs CHA | 28 | W 3-2 | 15-12 | 3 | 10,483 | Josh Tomlin | Eric Stults | Joe Smith | Matt Thornton | Tony Sipp | 128 | 124 | 4 |
| 2012-05-08 | vs CHA | 29 | L 3-5 | 16-13 | 2 | 11,304 | Justin Masterson | John Danks | Hector Santiago | Chris Perez | Addison Reed | 131 | 129 | 2 |
| 2012-05-09 | vs CHA | 30 | L 1-8 | 16-14 | 2 | 11,285 | Jeanmar Gomez | Jake Peavy | Jake Peavy | Jeanmar Gomez | | 132 | 137 | -5 |
| 2012-05-10 | @ BOS | 31 | W 8-3 | 17-14 | 1 | 37,348 | Derek Lowe | Josh Beckett | Derek Lowe | Josh Beckett | | 140 | 140 | 0 |
| 2012-05-11 | @ BOS | 32 | L 5-7 | 17-15 | 3 | 37,438 | Ubaldo Jimenez | Clay Buchholz | Clay Buchholz | Ubaldo Jimenez | Alfredo Aceves | 145 | 147 | -2 |
| 2012-05-12 | @ BOS | 33 | L 1-4 | 17-16 | 3 | 38,048 | Zach McAllister | Felix Doubront | Felix Doubront | Zach McAllister | Alfredo Aceves | 146 | 151 | -5 |
| 2012-05-13 | @ BOS | 34 | L 1-12 | 17-17 | 4 | 37,611 | Justin Masterson | Daniel Bard | Daniel Bard | Justin Masterson | | 147 | 163 | -16 |
| 2012-05-14 | @ MIN | 35 | W 5-4 | 18-17 | 4 | 32,313 | Jeanmar Gomez | Carl Pavano | Joe Smith | Matt Capps | Chris Perez | 152 | 167 | -15 |
| 2012-05-15 | @ MIN | 36 | W 5-0 | 19-17 | 3 | 35,732 | Derek Lowe | Jason Marquis | Derek Lowe | Jason Marquis | | 157 | 167 | -10 |
| 2012-05-16 | vs SEA | 37 | W 9-3 | 20-17 | 1 | 12,092 | Ubaldo Jimenez | Felix Hernandez | Ubaldo Jimenez | Felix Hernandez | | 166 | 170 | -4 |
| 2012-05-17 | vs SEA | 38 | W 6-5 | 21-17 | 1 | 12,894 | Zach McAllister | Hector Noesi | Joe Smith | Brandon League | | 172 | 175 | -3 |
| 2012-05-18 | vs MIA | 39 | L 2-3 | 21-18 | 2 | 29,378 | Justin Masterson | Carlos Zambrano | Carlos Zambrano | Tony Sipp | Heath Bell | 174 | 178 | -4 |
| 2012-05-19 | vs MIA | 40 | W 2-0 | 22-18 | 2 | 29,799 | Jeanmar Gomez | Anibal Sanchez | Jeanmar Gomez | Anibal Sanchez | Chris Perez | 176 | 178 | -2 |
| 2012-05-20 | vs MIA | 41 | L 3-5 | 22-19 | 2 | 23,668 | Derek Lowe | Josh Johnson | Josh Johnson | Derek Lowe | Heath Bell | 179 | 183 | -4 |
| 2012-05-22 | vs DET | 42 | W 5-3 | 23-19 | 2 | 15,049 | Ubaldo Jimenez | Rick Porcello | Ubaldo Jimenez | Rick Porcello | Chris Perez | 184 | 186 | -2 |
| 2012-05-23 | vs DET | 43 | W 4-2 | 24-19 | 2 | 22,000 | Zach McAllister | Doug Fister | Vinnie Pestano | Phil Coke | Chris Perez | 188 | 188 | 0 |
| 2012-05-24 | vs DET | 44 | W 2-1 | 25-19 | 1 | 23,622 | Justin Masterson | Justin Verlander | Justin Masterson | Justin Verlander | Chris Perez | 190 | 189 | 1 |
| 2012-05-25 | @ CHA | 45 | L 3-9 | 25-20 | 2 | 21,371 | Jeanmar Gomez | Jose Quintana | Jose Quintana | Jeanmar Gomez | | 193 | 198 | -5 |
| 2012-05-26 | @ CHA | 46 | W 7-14 | 26-20 | 1 | 27,151 | Derek Lowe | Jake Peavy | Jake Peavy | Derek Lowe | | 200 | 212 | -12 |
| 2012-05-27 | @ CHA | 47 | W 6-12 | 27-20 | 1 | 22,182 | Ubaldo Jimenez | Gavin Floyd | Gavin Floyd | Ubaldo Jimenez | | 206 | 224 | -18 |
| 2012-05-28 | vs KCA | 48 | W 8-5 | 28-20 | 1 | 25,377 | Josh Tomlin | Nathan Adcock | Josh Tomlin | Nathan Adcock | Chris Perez | 214 | 229 | -15 |
| 2012-05-29 | vs KCA | 49 | L 2-8 | 28-21 | 1 | 14,253 | Justin Masterson | Will Smith | Will Smith | Justin Masterson | | 216 | 237 | -21 |
| 2012-05-30 | vs KCA | 50 | L 3-6 | 28-22 | 2 | 17,112 | Jeanmar Gomez | Bruce Chen | Bruce Chen | Jeanmar Gomez | Jonathan Broxton | 219 | 243 | -24 |
| 2012-06-01 | vs MIN | 51 | W 7-1 | 29-22 | 2 | 19,904 | Derek Lowe | Carl Pavano | Derek Lowe | Carl Pavano | | 226 | 244 | -18 |
| 2012-06-02 | vs MIN | 52 | L 4-7 | 29-23 | 2 | 25,469 | Josh Tomlin | P.J. Walters | Brian Duensing | Josh Tomlin | Matt Capps | 230 | 251 | -21 |
| 2012-06-03 | vs MIN | 53 | L 3-6 | 29-24 | 2 | 21,238 | Justin Masterson | Scott Diamond | Scott Diamond | Justin Masterson | Matt Capps | 233 | 257 | -24 |
| 2012-06-05 | @ DET | 54 | W 4-2 | 30-24 | 2 | 33,258 | Ubaldo Jimenez | Drew Smyly | Ubaldo Jimenez | Drew Smyly | Chris Perez | 237 | 259 | -22 |
| 2012-06-06 | @ DET | 55 | W 9-6 | 31-24 | 2 | 31,350 | Jeanmar Gomez | Max Scherzer | Jeanmar Gomez | Max Scherzer | Chris Perez | 246 | 265 | -19 |
| 2012-06-07 | @ DET | 56 | L 5-7 | 31-25 | 2 | 40,851 | Derek Lowe | Casey Crosby | Casey Crosby | Derek Lowe | Jose Valverde | 251 | 272 | -21 |
| 2012-06-08 | @ SLN | 57 | W 6-2 | 32-25 | 2 | 42,098 | Josh Tomlin | Jake Westbrook | Josh Tomlin | Jake Westbrook | | 257 | 274 | -17 |
| 2012-06-09 | @ SLN | 58 | L 0-2 | 32-26 | 2 | 41,694 | Justin Masterson | Kyle Lohse | Kyle Lohse | Justin Masterson | Jason Motte | 257 | 276 | -19 |
| 2012-06-10 | @ SLN | 59 | W 4-1 | 33-26 | 2 | 43,400 | Ubaldo Jimenez | Joe Kelly | Vinnie Pestano | Jason Motte | Chris Perez | 261 | 277 | -16 |
| 2012-06-12 | @ CIN | 60 | L 1-7 | 33-27 | 2 | 24,758 | Jeanmar Gomez | Johnny Cueto | Johnny Cueto | Jeanmar Gomez | | 262 | 284 | -22 |
| 2012-06-13 | @ CIN | 61 | L 3-5 | 33-28 | 2 | 27,428 | Derek Lowe | Mat Latos | Mat Latos | Derek Lowe | Aroldis Chapman | 265 | 289 | -24 |
| 2012-06-14 | @ CIN | 62 | W 5-12 | 34-28 | 2 | 34,193 | Josh Tomlin | Mike Leake | Jose Arredondo | Josh Tomlin | | 270 | 301 | -31 |
| 2012-06-15 | vs PIT | 63 | W 2-0 | 35-28 | 2 | 31,920 | Justin Masterson | James McDonald | Justin Masterson | James McDonald | Chris Perez | 272 | 301 | -29 |
| 2012-06-16 | vs PIT | 64 | L 2-9 | 35-29 | 2 | 30,408 | Ubaldo Jimenez | A.J. Burnett | A.J. Burnett | Ubaldo Jimenez | | 274 | 310 | -36 |
| 2012-06-17 | vs PIT | 65 | L 5-9 | 35-30 | 3 | 27,388 | Jeanmar Gomez | Brad Lincoln | Tony Watson | Jeanmar Gomez | | 279 | 319 | -40 |
| 2012-06-18 | vs CIN | 66 | L 10-9 | 35-31 | 3 | 19,948 | Derek Lowe | Mat Latos | Joe Smith | Sam LeCure | Chris Perez | 289 | 328 | -39 |
| 2012-06-19 | vs CIN | 67 | W 3-2 | 36-31 | 3 | 17,213 | Josh Tomlin | Mike Leake | Nick Hagadone | Aroldis Chapman | | 292 | 330 | -38 |
| 2012-06-20 | vs CIN | 68 | W 8-1 | 37-31 | 3 | 23,544 | Justin Masterson | Bronson Arroyo | Justin Masterson | Bronson Arroyo | | 300 | 331 | -31 |
| 2012-06-22 | @ HOU | 69 | W 2-0 | 38-31 | 3 | 26,932 | Ubaldo Jimenez | Lucas Harrell | Ubaldo Jimenez | Lucas Harrell | Chris Perez | 302 | 331 | -29 |
| 2012-06-23 | @ HOU | 70 | L 1-8 | 38-32 | 3 | 34,241 | Jeanmar Gomez | Dallas Keuchel | Dallas Keuchel | Jeanmar Gomez | | 303 | 339 | -36 |
| 2012-06-24 | @ HOU | 71 | L 1-7 | 38-33 | 3 | 21,191 | Derek Lowe | J.A. Happ | J.A. Happ | Derek Lowe | | 304 | 346 | -42 |
| 2012-06-25 | @ NYA | 72 | L 1-7 | 38-34 | 3 | 42,290 | Josh Tomlin | Hiroki Kuroda | Hiroki Kuroda | Josh Tomlin | | 305 | 353 | -48 |
| 2012-06-26 | @ NYA | 73 | L 4-6 | 38-35 | 3 | 43,006 | Justin Masterson | Phil Hughes | Phil Hughes | Justin Masterson | Rafael Soriano | 309 | 359 | -50 |
| 2012-06-27 | @ NYA | 74 | L 4-5 | 38-36 | 4 | 45,099 | Ubaldo Jimenez | Andy Pettitte | Freddy Garcia | Ubaldo Jimenez | Rafael Soriano | 313 | 364 | -51 |
| 2012-06-28 | @ BAL | 75 | W 7-2 | 39-36 | 4 | 17,676 | Zach McAllister | Wei-Yin Chen | Zach McAllister | Wei-Yin Chen | | 320 | 366 | -46 |
| 2012-06-29 | @ BAL | 76 | L 8-9 | 39-37 | 4 | 24,779 | Derek Lowe | Jake Arrieta | Matt Lindstrom | Joe Smith | Jim Johnson | 328 | 375 | -47 |
| 2012-06-30 | @ BAL | 77 | L 11-5 | 39-38 | 5 | 35,335 | Josh Tomlin | Dana Eveland | Josh Tomlin | Dana Eveland | | 339 | 380 | -41 |
| 2012-07-01 | @ BAL | 78 | W 6-2 | 40-38 | 4 | 16,689 | Justin Masterson | Brian Matusz | Justin Masterson | Brian Matusz | | 345 | 382 | -37 |
| 2012-07-02 | vs ANA | 79 | L 0-3 | 40-39 | 4 | 21,616 | Ubaldo Jimenez | Jered Weaver | Jered Weaver | Ubaldo Jimenez | Scott Downs | 345 | 385 | -40 |
| 2012-07-03 | vs ANA | 80 | W 9-5 | 41-39 | 4 | 29,292 | Zach McAllister | Dan Haren | Zach McAllister | Dan Haren | | 354 | 390 | -36 |
| 2012-07-04 | vs ANA | 81 | L 12-3 | 41-40 | 4 | 20,979 | Derek Lowe | Ervin Santana | Derek Lowe | Ervin Santana | | 366 | 393 | -27 |
| 2012-07-05 | vs TBA | 82 | W 3-1 | 42-40 | 4 | 26,577 | Josh Tomlin | Jeremy Hellickson | Josh Tomlin | Jeremy Hellickson | Chris Perez | 369 | 394 | -25 |
| 2012-07-06 | vs TBA | 83 | W 3-10 | 43-40 | 4 | 28,734 | Justin Masterson | Alex Cobb | Alex Cobb | Justin Masterson | | 372 | 404 | -32 |
| 2012-07-07 | vs TBA | 84 | W 7-3 | 44-40 | 4 | 20,658 | Ubaldo Jimenez | Matt Moore | Ubaldo Jimenez | Matt Moore | | 379 | 407 | -28 |
| 2012-07-08 | vs TBA | 85 | L 6-7 | 44-41 | 4 | 19,163 | Zach McAllister | James Shields | Joel Peralta | Chris Perez | Fernando Rodney | 385 | 414 | -29 |
| 2012-07-13 | @ TOR | 86 | W 1-0 | 45-41 | 4 | 32,308 | Justin Masterson | Ricky Romero | Justin Masterson | Ricky Romero | Chris Perez | 386 | 414 | -28 |
| 2012-07-14 | @ TOR | 87 | W 9-11 | 46-41 | 4 | 32,517 | Ubaldo Jimenez | Aaron Laffey | Aaron Laffey | Ubaldo Jimenez | Casey Janssen | 395 | 425 | -30 |
| 2012-07-15 | @ TOR | 88 | L 0-3 | 46-42 | 4 | 26,407 | Derek Lowe | Carlos Villanueva | Carlos Villanueva | Derek Lowe | Darren Oliver | 395 | 428 | -33 |
| 2012-07-16 | @ TBA | 89 | W 3-2 | 47-42 | 3 | 14,337 | Zach McAllister | Alex Cobb | Zach McAllister | Alex Cobb | Chris Perez | 398 | 430 | -32 |
| 2012-07-17 | @ TBA | 90 | L 2-4 | 47-43 | 3 | 15,712 | Josh Tomlin | Matt Moore | Matt Moore | Josh Tomlin | Fernando Rodney | 400 | 434 | -34 |
| 2012-07-18 | @ TBA | 91 | L 10-6 | 47-44 | 4 | 15,143 | Justin Masterson | Jeremy Hellickson | Esmil Rogers | Kyle Farnsworth | | 410 | 440 | -30 |
| 2012-07-19 | @ TBA | 92 | L 0-6 | 47-45 | 4 | 27,856 | Ubaldo Jimenez | David Price | David Price | Ubaldo Jimenez | | 410 | 446 | -36 |
| 2012-07-20 | vs BAL | 93 | W 2-10 | 48-45 | 3 | 33,954 | Derek Lowe | Miguel Gonzalez | Miguel Gonzalez | Derek Lowe | | 412 | 456 | -44 |
| 2012-07-21 | vs BAL | 94 | L 1-3 | 48-46 | 4 | 36,247 | Zach McAllister | Chris Tillman | Chris Tillman | Zach McAllister | Jim Johnson | 413 | 459 | -46 |
| 2012-07-22 | vs BAL | 95 | L 3-4 | 48-47 | 4 | 28,049 | Josh Tomlin | Zachary Britton | Zachary Britton | Josh Tomlin | Jim Johnson | 416 | 463 | -47 |
| 2012-07-23 | vs BAL | 96 | W 3-1 | 49-47 | 3 | 18,264 | Justin Masterson | Tommy Hunter | Justin Masterson | Tommy Hunter | Chris Perez | 419 | 464 | -45 |
| 2012-07-24 | vs DET | 97 | W 3-2 | 50-47 | 3 | 23,637 | Ubaldo Jimenez | Doug Fister | Joe Smith | Doug Fister | Chris Perez | 422 | 466 | -44 |
| 2012-07-25 | vs DET | 98 | L 3-5 | 50-48 | 4 | 24,029 | Derek Lowe | Max Scherzer | Max Scherzer | Derek Lowe | Jose Valverde | 425 | 471 | -46 |
| 2012-07-26 | vs DET | 99 | W 5-3 | 51-48 | 3 | 34,579 | Zach McAllister | Justin Verlander | Joe Smith | Justin Verlander | Chris Perez | 430 | 474 | -44 |
| 2012-07-27 | @ MIN | 100 | L 0-11 | 51-49 | 3 | 37,820 | Josh Tomlin | Scott Diamond | Scott Diamond | Josh Tomlin | | 430 | 485 | -55 |
| 2012-07-28 | @ MIN | 101 | W 5-12 | 52-49 | 3 | 39,166 | Justin Masterson | Samuel Deduno | Samuel Deduno | Justin Masterson | | 435 | 497 | -62 |
| 2012-07-29 | @ MIN | 102 | L 1-5 | 52-50 | 3 | 34,720 | Ubaldo Jimenez | Brian Duensing | Brian Duensing | Ubaldo Jimenez | | 436 | 502 | -66 |
| 2012-07-31 | @ KCA | 103 | L 3-8 | 52-51 | 3 | 18,569 | Derek Lowe | Luke Hochevar | Luke Hochevar | Derek Lowe | | 439 | 510 | -71 |
| 2012-08-01 | @ KCA | 104 | L 2-5 | 52-52 | 4 | 17,033 | Zach McAllister | Luis Mendoza | Luis Mendoza | Zach McAllister | Greg Holland | 441 | 515 | -74 |
| 2012-08-02 | @ KCA | 105 | L 6-7 | 52-53 | 4 | 15,135 | Corey Kluber | Bruce Chen | Aaron Crow | Esmil Rogers | | 447 | 522 | -75 |
| 2012-08-03 | @ DET | 106 | W 2-10 | 53-53 | 4 | 41,502 | Justin Masterson | Anibal Sanchez | Anibal Sanchez | Justin Masterson | | 449 | 532 | -83 |
| 2012-08-04 | @ DET | 107 | L 1-6 | 53-54 | 4 | 42,744 | Ubaldo Jimenez | Doug Fister | Doug Fister | Ubaldo Jimenez | | 450 | 538 | -88 |
| 2012-08-05 | @ DET | 108 | W 8-10 | 54-54 | 4 | 38,007 | Chris Seddon | Max Scherzer | Darin Downs | Chris Perez | | 458 | 548 | -90 |
| 2012-08-06 | vs MIN | 109 | W 3-14 | 55-54 | 3 | 18,775 | Zach McAllister | Scott Diamond | Scott Diamond | Zach McAllister | | 461 | 562 | -101 |
| 2012-08-07 | vs MIN | 110 | L 5-7 | 55-55 | 4 | 14,813 | Corey Kluber | Samuel Deduno | Tyler Robertson | Chris Perez | Glen Perkins | 466 | 569 | -103 |
| 2012-08-08 | vs MIN | 111 | W 6-2 | 56-55 | 4 | 18,805 | Justin Masterson | Brian Duensing | Justin Masterson | Brian Duensing | | 472 | 571 | -99 |
| 2012-08-09 | vs BOS | 112 | W 5-3 | 57-55 | 4 | 19,639 | Ubaldo Jimenez | Felix Doubront | Ubaldo Jimenez | Felix Doubront | Chris Perez | 477 | 574 | -97 |
| 2012-08-10 | vs BOS | 113 | L 2-3 | 57-56 | 4 | 27,246 | Chris Seddon | Clay Buchholz | Clay Buchholz | Chris Seddon | | 479 | 577 | -98 |
| 2012-08-11 | vs BOS | 114 | W 5-2 | 58-56 | 4 | 27,894 | Zach McAllister | Franklin Morales | Zach McAllister | Franklin Morales | Chris Perez | 484 | 579 | -95 |
| 2012-08-12 | vs BOS | 115 | L 1-14 | 58-57 | 4 | 27,488 | Corey Kluber | Jon Lester | Jon Lester | Corey Kluber | | 485 | 593 | -108 |
| 2012-08-13 | @ ANA | 116 | W 6-2 | 59-57 | 4 | 36,620 | Justin Masterson | C.J. Wilson | Justin Masterson | C.J. Wilson | Chris Perez | 491 | 595 | -104 |
| 2012-08-14 | @ ANA | 117 | L 6-9 | 59-58 | 4 | 39,827 | Ubaldo Jimenez | Zack Greinke | Zack Greinke | Ubaldo Jimenez | Ernesto Frieri | 497 | 604 | -107 |
| 2012-08-15 | @ ANA | 118 | L 4-8 | 59-59 | 4 | 37,554 | Fausto Carmona | Ervin Santana | Ervin Santana | Fausto Carmona | | 501 | 612 | -111 |
| 2012-08-17 | @ OAK | 119 | L 4-6 | 59-60 | 4 | 13,967 | Zach McAllister | Tom Milone | Jordan Norberto | Joe Smith | Grant Balfour | 505 | 618 | -113 |
| 2012-08-18 | @ OAK | 120 | L 5-8 | 59-61 | 4 | 30,132 | Corey Kluber | Bartolo Colon | Bartolo Colon | Corey Kluber | Grant Balfour | 510 | 626 | -116 |
| 2012-08-19 | @ OAK | 121 | L 0-7 | 59-62 | 4 | 20,130 | Justin Masterson | Jarrod Parker | Jarrod Parker | Justin Masterson | | 510 | 633 | -123 |
| 2012-08-20 | @ SEA | 122 | L 3-5 | 59-63 | 4 | 14,687 | Ubaldo Jimenez | Kevin Millwood | Charlie Furbush | Joe Smith | Tom Wilhelmsen | 513 | 638 | -125 |
| 2012-08-21 | @ SEA | 123 | L 1-5 | 59-64 | 4 | 39,204 | Fausto Carmona | Felix Hernandez | Felix Hernandez | Fausto Carmona | Lucas Luetge | 514 | 643 | -129 |
| 2012-08-22 | @ SEA | 124 | L 1-3 | 59-65 | 4 | 18,578 | Zach McAllister | Hisashi Iwakuma | Stephen Pryor | Vinnie Pestano | Tom Wilhelmsen | 515 | 646 | -131 |
| 2012-08-24 | vs NYA | 125 | L 1-3 | 59-66 | 4 | 27,986 | Corey Kluber | CC Sabathia | CC Sabathia | Cody Allen | Rafael Soriano | 516 | 649 | -133 |
| 2012-08-25 | vs NYA | 126 | W 3-1 | 60-66 | 4 | 34,374 | Justin Masterson | Hiroki Kuroda | Justin Masterson | Hiroki Kuroda | Chris Perez | 519 | 650 | -131 |
| 2012-08-26 | vs NYA | 127 | L 2-4 | 60-67 | 4 | 26,166 | Ubaldo Jimenez | Freddy Garcia | Boone Logan | Ubaldo Jimenez | Rafael Soriano | 521 | 654 | -133 |
| 2012-08-27 | vs OAK | 128 | L 0-3 | 60-68 | 4 | 13,018 | Fausto Carmona | Brett Anderson | Brett Anderson | Fausto Carmona | Grant Balfour | 521 | 657 | -136 |
| 2012-08-28 | vs OAK | 129 | L 0-7 | 60-69 | 4 | 13,413 | Zach McAllister | Tom Milone | Tom Milone | Zach McAllister | | 521 | 664 | -143 |
| 2012-08-29 | vs OAK | 130 | L 4-8 | 60-70 | 4 | 14,412 | Corey Kluber | Travis Blackley | Travis Blackley | Corey Kluber | Ryan Cook | 525 | 672 | -147 |
| 2012-08-30 | vs OAK | 131 | W 7-12 | 61-70 | 4 | 14,500 | Justin Masterson | Jarrod Parker | Jarrod Parker | Justin Masterson | | 532 | 684 | -152 |
| 2012-08-31 | vs TEX | 132 | L 3-5 | 61-71 | 4 | 16,700 | Ubaldo Jimenez | Ryan Dempster | Ryan Dempster | Ubaldo Jimenez | Joe Nathan | 535 | 689 | -154 |
| 2012-09-01 | vs TEX | 133 | W 4-3 | 62-71 | 5 | 17,218 | Jeanmar Gomez | Scott Feldman | Jeanmar Gomez | Scott Feldman | Vinnie Pestano | 539 | 692 | -153 |
| 2012-09-02 | vs TEX | 134 | L 3-8 | 62-72 | 4 | 19,474 | Zach McAllister | Derek Holland | Derek Holland | Zach McAllister | | 542 | 700 | -158 |
| 2012-09-03 | @ DET | 135 | W 3-2 | 63-72 | 4 | 35,418 | Corey Kluber | Anibal Sanchez | Corey Kluber | Darin Downs | Vinnie Pestano | 545 | 702 | -157 |
| 2012-09-04 | @ DET | 136 | W 3-2 | 64-72 | 4 | 27,729 | Justin Masterson | Rick Porcello | Justin Masterson | Rick Porcello | Chris Perez | 548 | 704 | -156 |
| 2012-09-05 | @ DET | 137 | L 1-7 | 64-73 | 4 | 28,881 | Ubaldo Jimenez | Doug Fister | Doug Fister | Ubaldo Jimenez | | 549 | 711 | -162 |
| 2012-09-07 | @ MIN | 138 | W 7-6 | 65-73 | 4 | 30,111 | Jeanmar Gomez | Liam Hendriks | David Huff | Tyler Robertson | Chris Perez | 556 | 717 | -161 |
| 2012-09-08 | @ MIN | 139 | L 0-3 | 65-74 | 4 | 33,698 | Zach McAllister | Cole De Vries | Cole De Vries | Zach McAllister | Glen Perkins | 556 | 720 | -164 |
| 2012-09-09 | @ MIN | 140 | L 7-8 | 65-75 | 4 | 30,219 | Corey Kluber | Esmerling Vasquez | Brian Duensing | Vinnie Pestano | | 563 | 728 | -165 |
| 2012-09-10 | @ MIN | 141 | L 2-7 | 65-76 | 4 | 27,526 | Justin Masterson | Samuel Deduno | Samuel Deduno | Justin Masterson | | 565 | 735 | -170 |
| 2012-09-11 | @ TEX | 142 | L 4-6 | 65-77 | 4 | 34,765 | Ubaldo Jimenez | Matt Harrison | Matt Harrison | Ubaldo Jimenez | Joe Nathan | 569 | 741 | -172 |
| 2012-09-12 | @ TEX | 143 | L 2-5 | 65-78 | 4 | 36,001 | Jeanmar Gomez | Ryan Dempster | Ryan Dempster | Jeanmar Gomez | Joe Nathan | 571 | 746 | -175 |
| 2012-09-13 | @ TEX | 144 | W 5-4 | 66-78 | 4 | 36,102 | Zach McAllister | Derek Holland | Scott Maine | Joe Nathan | Chris Perez | 576 | 750 | -174 |
| 2012-09-14 | vs DET | 145 | L 0-4 | 66-79 | 4 | 17,185 | Corey Kluber | Justin Verlander | Justin Verlander | Corey Kluber | | 576 | 754 | -178 |
| 2012-09-15 | vs DET | 146 | L 3-5 | 66-80 | 4 | 22,849 | Justin Masterson | Anibal Sanchez | Anibal Sanchez | Justin Masterson | Jose Valverde | 579 | 759 | -180 |
| 2012-09-16 | vs DET | 147 | W 7-6 | 67-80 | 4 | 17,233 | Ubaldo Jimenez | Rick Porcello | Esmil Rogers | Jose Valverde | | 586 | 765 | -179 |
| 2012-09-18 | vs MIN | 148 | L 5-6 | 67-81 | 4 | 10,342 | David Huff | P.J. Walters | Tyler Robertson | Scott Maine | Glen Perkins | 591 | 771 | -180 |
| 2012-09-19 | vs MIN | 149 | L 4-6 | 67-82 | 4 | 13,519 | Zach McAllister | Liam Hendriks | Liam Hendriks | Zach McAllister | Glen Perkins | 595 | 777 | -182 |
| 2012-09-20 | vs MIN | 150 | W 4-3 | 68-82 | 4 | 12,331 | Corey Kluber | Esmerling Vasquez | Esmil Rogers | Anthony Swarzak | | 599 | 780 | -181 |
| 2012-09-21 | @ KCA | 151 | L 3-6 | 68-83 | 4 | 22,805 | Justin Masterson | Luis Mendoza | Luis Mendoza | Justin Masterson | Greg Holland | 602 | 786 | -184 |
| 2012-09-22 | @ KCA | 152 | L 3-5 | 68-84 | 4 | 24,304 | Ubaldo Jimenez | Will Smith | Will Smith | Ubaldo Jimenez | Kelvin Herrera | 605 | 791 | -186 |
| 2012-09-23 | @ KCA | 153 | L 15-4 | 68-85 | 5 | 22,960 | David Huff | Jake Odorizzi | David Huff | Jake Odorizzi | | 620 | 795 | -175 |
| 2012-09-24 | @ CHA | 154 | L 4-5 | 68-86 | 4 | 20,206 | Zach McAllister | Chris Sale | Brett Myers | Vinnie Pestano | Donald Veal | 624 | 800 | -176 |
| 2012-09-25 | @ CHA | 155 | W 4-3 | 69-86 | 4 | 13,797 | Corey Kluber | Francisco Liriano | Corey Kluber | Francisco Liriano | Chris Perez | 628 | 803 | -175 |
| 2012-09-26 | @ CHA | 156 | W 6-4 | 70-86 | 4 | 20,166 | Justin Masterson | Hector Santiago | Tony Sipp | Matt Thornton | Chris Perez | 634 | 807 | -173 |
| 2012-09-28 | vs KCA | 157 | W 8-5 | 71-86 | 4 | 14,850 | David Huff | Will Smith | David Huff | Will Smith | Chris Perez | 642 | 812 | -170 |
| 2012-09-29 | vs KCA | 158 | L 6-7 | 71-87 | 4 | 17,109 | Jeanmar Gomez | Jake Odorizzi | Vin Mazzaro | Scott Maine | Kelvin Herrera | 648 | 819 | -171 |
| 2012-09-30 | vs KCA | 159 | L 15-3 | 71-88 | 4 | 18,099 | Zach McAllister | Luke Hochevar | Zach McAllister | Luke Hochevar | | 663 | 822 | -159 |
| 2012-10-01 | vs CHA | 160 | L 0-11 | 71-89 | 4 | 14,756 | Corey Kluber | Hector Santiago | Hector Santiago | Corey Kluber | | 663 | 833 | -170 |
| 2012-10-02 | vs CHA | 161 | W 4-3 | 72-89 | 4 | 10,015 | Justin Masterson | Jake Peavy | Chris Seddon | Matt Thornton | | 667 | 836 | -169 |
| 2012-10-03 | vs CHA | 162 | L 0-9 | 72-90 | 4 | 18,093 | David Huff | Gavin Floyd | Gavin Floyd | David Huff | | 667 | 845 | -178 |