| 2012-04-06 | @ TEX | 1 | L 2-3 | 0-1 | 2 | 49,085 | John Danks | Colby Lewis | Colby Lewis | John Danks | Joe Nathan | 2 | 3 | -1 |
| 2012-04-07 | @ TEX | 2 | W 4-3 | 1-1 | 2 | 47,867 | Jake Peavy | Derek Holland | Matt Thornton | Joe Nathan | Hector Santiago | 6 | 6 | 0 |
| 2012-04-08 | @ TEX | 3 | L 0-5 | 1-2 | 3 | 45,368 | Gavin Floyd | Matt Harrison | Matt Harrison | Gavin Floyd | | 6 | 11 | -5 |
| 2012-04-09 | @ CLE | 4 | W 4-2 | 2-2 | 2 | 9,473 | Chris Sale | Josh Tomlin | Chris Sale | Josh Tomlin | Hector Santiago | 10 | 13 | -3 |
| 2012-04-11 | @ CLE | 5 | L 10-6 | 2-3 | 3 | 9,072 | John Danks | Justin Masterson | John Danks | Justin Masterson | | 20 | 19 | 1 |
| 2012-04-13 | vs DET | 6 | W 5-2 | 3-3 | 2 | 38,676 | Jake Peavy | Max Scherzer | Jake Peavy | Max Scherzer | Hector Santiago | 25 | 21 | 4 |
| 2012-04-14 | vs DET | 7 | W 5-1 | 4-3 | 2 | 33,025 | Gavin Floyd | Adam Wilk | Gavin Floyd | Adam Wilk | | 30 | 22 | 8 |
| 2012-04-15 | vs DET | 8 | L 2-5 | 4-4 | 3 | 25,143 | Chris Sale | Rick Porcello | Rick Porcello | Chris Sale | | 32 | 27 | 5 |
| 2012-04-16 | vs BAL | 9 | W 4-10 | 5-4 | 2 | 13,732 | Philip Humber | Jake Arrieta | Pedro Strop | Zach Stewart | | 36 | 37 | -1 |
| 2012-04-17 | vs BAL | 10 | L 2-3 | 5-5 | 2 | 11,267 | John Danks | Wei-Yin Chen | Wei-Yin Chen | John Danks | Jim Johnson | 38 | 40 | -2 |
| 2012-04-18 | vs BAL | 11 | W 8-1 | 6-5 | 2 | 13,818 | Jake Peavy | Tommy Hunter | Jake Peavy | Tommy Hunter | | 46 | 41 | 5 |
| 2012-04-19 | vs BAL | 12 | L 3-5 | 6-6 | 2 | 11,836 | Gavin Floyd | Jason Hammel | Jason Hammel | Gavin Floyd | Jim Johnson | 49 | 46 | 3 |
| 2012-04-20 | @ SEA | 13 | W 7-3 | 7-6 | 2 | 19,947 | Chris Sale | Hector Noesi | Chris Sale | Hector Noesi | | 56 | 49 | 7 |
| 2012-04-21 | @ SEA | 14 | W 4-0 | 8-6 | 3 | 22,472 | Philip Humber | Blake Beavan | Philip Humber | Blake Beavan | | 60 | 49 | 11 |
| 2012-04-22 | @ SEA | 15 | W 7-4 | 9-6 | 2 | 19,975 | John Danks | Kevin Millwood | John Danks | Kevin Millwood | Hector Santiago | 67 | 53 | 14 |
| 2012-04-23 | @ OAK | 16 | W 4-0 | 10-6 | 2 | 10,574 | Jake Peavy | Bartolo Colon | Jake Peavy | Bartolo Colon | | 71 | 53 | 18 |
| 2012-04-24 | @ OAK | 17 | L 0-2 | 10-7 | 2 | 11,184 | Gavin Floyd | Tom Milone | Tom Milone | Gavin Floyd | Grant Balfour | 71 | 55 | 16 |
| 2012-04-25 | @ OAK | 18 | L 4-5 | 10-8 | 2 | 13,032 | Chris Sale | Jarrod Parker | Jim Miller | Hector Santiago | | 75 | 60 | 15 |
| 2012-04-26 | vs BOS | 19 | W 3-10 | 11-8 | 2 | 20,266 | Philip Humber | Felix Doubront | Felix Doubront | Philip Humber | Junichi Tazawa | 78 | 70 | 8 |
| 2012-04-27 | vs BOS | 20 | W 3-10 | 12-8 | 1 | 20,414 | John Danks | Daniel Bard | Daniel Bard | John Danks | | 81 | 80 | 1 |
| 2012-04-28 | vs BOS | 21 | L 0-1 | 12-9 | 2 | 20,057 | Jake Peavy | Jon Lester | Jon Lester | Jake Peavy | Alfredo Aceves | 81 | 81 | 0 |
| 2012-04-29 | vs BOS | 22 | W 4-1 | 13-9 | 1 | 22,811 | Gavin Floyd | Josh Beckett | Gavin Floyd | Josh Beckett | Matt Thornton | 85 | 82 | 3 |
| 2012-05-01 | vs CLE | 23 | W 7-2 | 14-9 | 1 | 15,212 | Chris Sale | Ubaldo Jimenez | Chris Sale | Ubaldo Jimenez | | 92 | 84 | 8 |
| 2012-05-02 | vs CLE | 24 | L 3-6 | 14-10 | 1 | 15,192 | Philip Humber | Josh Tomlin | Joe Smith | Will Ohman | Chris Perez | 95 | 90 | 5 |
| 2012-05-03 | vs CLE | 25 | L 5-7 | 14-11 | 2 | 17,314 | John Danks | Justin Masterson | Justin Masterson | John Danks | Chris Perez | 100 | 97 | 3 |
| 2012-05-04 | @ DET | 26 | L 4-5 | 14-12 | 3 | 33,615 | Jake Peavy | Drew Smyly | Jose Valverde | Matt Thornton | | 104 | 102 | 2 |
| 2012-05-05 | @ DET | 27 | W 3-2 | 15-12 | 2 | 42,404 | Gavin Floyd | Max Scherzer | Nate Jones | Jose Valverde | Addison Reed | 107 | 104 | 3 |
| 2012-05-06 | @ DET | 28 | L 1-3 | 15-13 | 3 | 39,558 | Dylan Axelrod | Rick Porcello | Rick Porcello | Dylan Axelrod | Jose Valverde | 108 | 107 | 1 |
| 2012-05-07 | @ CLE | 29 | L 6-8 | 15-15 | 5 | 9,196 | Philip Humber | Zach McAllister | Zach McAllister | Philip Humber | Nick Hagadone | 114 | 115 | -1 |
| 2012-05-07 | @ CLE | 30 | L 2-3 | 15-15 | 5 | 10,483 | Eric Stults | Josh Tomlin | Joe Smith | Matt Thornton | Tony Sipp | 116 | 118 | -2 |
| 2012-05-08 | @ CLE | 31 | W 5-3 | 16-15 | 3 | 11,304 | John Danks | Justin Masterson | Hector Santiago | Chris Perez | Addison Reed | 121 | 121 | 0 |
| 2012-05-09 | @ CLE | 32 | W 8-1 | 17-15 | 3 | 11,285 | Jake Peavy | Jeanmar Gomez | Jake Peavy | Jeanmar Gomez | | 129 | 122 | 7 |
| 2012-05-11 | vs KCA | 33 | W 5-0 | 18-15 | 2 | 19,129 | Gavin Floyd | Felipe Paulino | Gavin Floyd | Felipe Paulino | | 134 | 122 | 12 |
| 2012-05-12 | vs KCA | 34 | L 0-5 | 18-16 | 2 | 20,066 | Chris Sale | Luke Hochevar | Luke Hochevar | Chris Sale | | 134 | 127 | 7 |
| 2012-05-13 | vs KCA | 35 | L 1-9 | 18-17 | 3 | 22,636 | Philip Humber | Danny Duffy | Luis Mendoza | Matt Thornton | | 135 | 136 | -1 |
| 2012-05-14 | vs DET | 36 | W 7-5 | 19-17 | 3 | 23,538 | John Danks | Drew Smyly | Zach Stewart | Luke Putkonen | Addison Reed | 142 | 141 | 1 |
| 2012-05-15 | vs DET | 37 | W 8-10 | 20-17 | 2 | 21,473 | Jake Peavy | Max Scherzer | Collin Balester | Will Ohman | Octavio Dotel | 150 | 151 | -1 |
| 2012-05-16 | @ ANA | 38 | L 2-7 | 20-18 | 4 | 39,027 | Gavin Floyd | Jerome Williams | Jerome Williams | Gavin Floyd | | 152 | 158 | -6 |
| 2012-05-17 | @ ANA | 39 | W 6-1 | 21-18 | 2 | 30,786 | Chris Sale | C.J. Wilson | Chris Sale | C.J. Wilson | | 158 | 159 | -1 |
| 2012-05-18 | @ CHN | 40 | W 3-2 | 22-18 | 1 | 34,937 | Philip Humber | Jeff Samardzija | Matt Thornton | Jeff Samardzija | Addison Reed | 161 | 161 | 0 |
| 2012-05-19 | @ CHN | 41 | W 7-4 | 23-18 | 1 | 40,228 | John Danks | Ryan Dempster | John Danks | Ryan Dempster | | 168 | 165 | 3 |
| 2012-05-20 | @ CHN | 42 | W 6-0 | 24-18 | 1 | 38,374 | Jake Peavy | Paul Maholm | Jake Peavy | Paul Maholm | | 174 | 165 | 9 |
| 2012-05-22 | vs MIN | 43 | L 2-9 | 24-19 | 1 | 20,026 | Gavin Floyd | P.J. Walters | P.J. Walters | Gavin Floyd | | 176 | 174 | 2 |
| 2012-05-23 | vs MIN | 44 | W 6-0 | 25-19 | 1 | 20,064 | Chris Sale | Scott Diamond | Chris Sale | Scott Diamond | | 182 | 174 | 8 |
| 2012-05-24 | vs MIN | 45 | L 11-8 | 25-20 | 2 | 20,167 | Philip Humber | Cole De Vries | Nate Jones | Cole De Vries | | 193 | 182 | 11 |
| 2012-05-25 | vs CLE | 46 | W 9-3 | 26-20 | 1 | 21,371 | Jose Quintana | Jeanmar Gomez | Jose Quintana | Jeanmar Gomez | | 202 | 185 | 17 |
| 2012-05-26 | vs CLE | 47 | L 14-7 | 26-21 | 2 | 27,151 | Jake Peavy | Derek Lowe | Jake Peavy | Derek Lowe | | 216 | 192 | 24 |
| 2012-05-27 | vs CLE | 48 | L 12-6 | 26-22 | 2 | 22,182 | Gavin Floyd | Ubaldo Jimenez | Gavin Floyd | Ubaldo Jimenez | | 228 | 198 | 30 |
| 2012-05-28 | @ TBA | 49 | W 2-1 | 27-22 | 2 | 22,227 | Chris Sale | Matt Moore | Chris Sale | Matt Moore | Addison Reed | 230 | 199 | 31 |
| 2012-05-29 | @ TBA | 50 | W 7-2 | 28-22 | 2 | 13,735 | Philip Humber | James Shields | Philip Humber | James Shields | | 237 | 201 | 36 |
| 2012-05-30 | @ TBA | 51 | W 4-3 | 29-22 | 1 | 13,369 | Jose Quintana | Alex Cobb | Nate Jones | Alex Cobb | Addison Reed | 241 | 204 | 37 |
| 2012-06-01 | vs SEA | 52 | W 7-4 | 30-22 | 1 | 19,168 | Jake Peavy | Felix Hernandez | Jesse Crain | Shawn Kelley | Addison Reed | 248 | 208 | 40 |
| 2012-06-02 | vs SEA | 53 | W 8-10 | 31-22 | 1 | 26,200 | Gavin Floyd | Hector Noesi | Tom Wilhelmsen | Addison Reed | Hisashi Iwakuma | 256 | 218 | 38 |
| 2012-06-03 | vs SEA | 54 | W 4-2 | 32-22 | 1 | 23,062 | Chris Sale | Kevin Millwood | Chris Sale | Kevin Millwood | | 260 | 220 | 40 |
| 2012-06-05 | vs TOR | 55 | L 5-9 | 32-23 | 1 | 23,107 | Philip Humber | Ricky Romero | Ricky Romero | Philip Humber | | 265 | 229 | 36 |
| 2012-06-06 | vs TOR | 56 | L 0-4 | 32-24 | 1 | 25,672 | Jose Quintana | Brandon Morrow | Brandon Morrow | Jose Quintana | | 265 | 233 | 32 |
| 2012-06-07 | vs TOR | 57 | W 4-3 | 33-24 | 1 | 25,743 | Jake Peavy | Henderson Alvarez | Addison Reed | Francisco Cordero | | 269 | 236 | 33 |
| 2012-06-08 | vs HOU | 58 | L 3-8 | 33-25 | 1 | 22,452 | Gavin Floyd | Wandy Rodriguez | Wandy Rodriguez | Gavin Floyd | | 272 | 244 | 28 |
| 2012-06-09 | vs HOU | 59 | W 10-1 | 34-25 | 1 | 22,880 | Chris Sale | Jordan Lyles | Chris Sale | Jordan Lyles | | 282 | 245 | 37 |
| 2012-06-10 | vs HOU | 60 | W 9-11 | 35-25 | 1 | 20,398 | Philip Humber | Lucas Harrell | Lucas Harrell | Philip Humber | Brett Myers | 291 | 256 | 35 |
| 2012-06-12 | @ SLN | 61 | W 6-1 | 36-25 | 1 | 40,972 | Jose Quintana | Adam Wainwright | Jose Quintana | Adam Wainwright | | 297 | 257 | 40 |
| 2012-06-13 | @ SLN | 62 | L 0-1 | 36-26 | 1 | 40,045 | Jake Peavy | Lance Lynn | Lance Lynn | Jake Peavy | Jason Motte | 297 | 258 | 39 |
| 2012-06-14 | @ SLN | 63 | L 3-5 | 36-27 | 1 | 43,464 | Gavin Floyd | Jake Westbrook | Jake Westbrook | Gavin Floyd | Jason Motte | 300 | 263 | 37 |
| 2012-06-15 | @ LAN | 64 | L 6-7 | 36-28 | 1 | 40,432 | Chris Sale | Clayton Kershaw | Ronald Belisario | Matt Thornton | Kenley Jansen | 306 | 270 | 36 |
| 2012-06-16 | @ LAN | 65 | W 5-4 | 37-28 | 1 | 45,210 | Philip Humber | Chad Billingsley | Philip Humber | Chad Billingsley | Addison Reed | 311 | 274 | 37 |
| 2012-06-17 | @ LAN | 66 | L 1-2 | 37-29 | 1 | 53,504 | Jose Quintana | Chris Capuano | Ronald Belisario | Matt Thornton | | 312 | 276 | 36 |
| 2012-06-18 | vs CHN | 67 | W 3-12 | 38-29 | 1 | 33,215 | Zach Stewart | Matt Garza | Matt Garza | Zach Stewart | | 315 | 288 | 27 |
| 2012-06-19 | vs CHN | 68 | L 1-2 | 38-30 | 1 | 30,282 | Jake Peavy | Travis Wood | Travis Wood | Jake Peavy | Carlos Marmol | 316 | 290 | 26 |
| 2012-06-20 | vs CHN | 69 | W 7-0 | 39-30 | 1 | 32,311 | Gavin Floyd | Randy Wells | Gavin Floyd | Randy Wells | | 323 | 290 | 33 |
| 2012-06-22 | vs MIL | 70 | L 0-1 | 39-31 | 2 | 22,798 | Chris Sale | Zack Greinke | Zack Greinke | Jesse Crain | John Axford | 323 | 291 | 32 |
| 2012-06-23 | vs MIL | 71 | W 8-6 | 40-31 | 1 | 30,337 | Dylan Axelrod | Randy Wolf | Jesse Crain | Jose Veras | Addison Reed | 331 | 297 | 34 |
| 2012-06-24 | vs MIL | 72 | W 1-0 | 41-31 | 1 | 26,545 | Jose Quintana | Michael Fiers | Brian Bruney | Manny Parra | | 332 | 297 | 35 |
| 2012-06-25 | @ MIN | 73 | L 1-4 | 41-32 | 2 | 35,659 | Jake Peavy | Francisco Liriano | Francisco Liriano | Jake Peavy | Jared Burton | 333 | 301 | 32 |
| 2012-06-26 | @ MIN | 74 | W 3-2 | 42-32 | 2 | 35,102 | Gavin Floyd | Liam Hendriks | Gavin Floyd | Liam Hendriks | Addison Reed | 336 | 303 | 33 |
| 2012-06-27 | @ MIN | 75 | L 12-5 | 42-33 | 2 | 36,539 | Chris Sale | Nick Blackburn | Chris Sale | Nick Blackburn | | 348 | 308 | 40 |
| 2012-06-28 | @ NYA | 76 | W 4-3 | 43-33 | 2 | 44,041 | Dylan Axelrod | Ivan Nova | Hector Santiago | David Robertson | Addison Reed | 352 | 311 | 41 |
| 2012-06-29 | @ NYA | 77 | L 14-7 | 43-34 | 2 | 44,265 | Jose Quintana | Adam Warren | Jose Quintana | David Phelps | | 366 | 318 | 48 |
| 2012-06-30 | @ NYA | 78 | L 0-4 | 43-35 | 3 | 46,895 | Jake Peavy | Hiroki Kuroda | Hiroki Kuroda | Jake Peavy | | 366 | 322 | 44 |
| 2012-07-01 | @ NYA | 79 | L 2-4 | 43-36 | 2 | 48,324 | Gavin Floyd | Phil Hughes | Phil Hughes | Gavin Floyd | Rafael Soriano | 368 | 326 | 42 |
| 2012-07-03 | vs TEX | 80 | L 19-2 | 43-37 | 2 | 30,183 | Chris Sale | Roy Oswalt | Chris Sale | Roy Oswalt | | 387 | 328 | 59 |
| 2012-07-04 | vs TEX | 81 | W 5-4 | 44-37 | 2 | 30,271 | Dylan Axelrod | Scott Feldman | Addison Reed | Mike Adams | | 392 | 332 | 60 |
| 2012-07-05 | vs TEX | 82 | W 2-1 | 45-37 | 2 | 21,288 | Jose Quintana | Matt Harrison | Jose Quintana | Matt Harrison | Addison Reed | 394 | 333 | 61 |
| 2012-07-06 | vs TOR | 83 | W 4-2 | 46-37 | 1 | 27,129 | Jake Peavy | Aaron Laffey | Jake Peavy | Aaron Laffey | Addison Reed | 398 | 335 | 63 |
| 2012-07-07 | vs TOR | 84 | W 2-0 | 47-37 | 1 | 25,399 | Gavin Floyd | Ricky Romero | Gavin Floyd | Ricky Romero | Matt Thornton | 400 | 335 | 65 |
| 2012-07-08 | vs TOR | 85 | W 9-11 | 48-37 | 1 | 27,190 | Dylan Axelrod | Brett Cecil | Jason Frasor | Dylan Axelrod | Casey Janssen | 409 | 346 | 63 |
| 2012-07-13 | @ KCA | 86 | W 9-8 | 49-37 | 1 | 32,744 | Jose Quintana | Bruce Chen | Dylan Axelrod | Everett Teaford | | 418 | 354 | 64 |
| 2012-07-14 | @ KCA | 87 | L 3-6 | 49-38 | 1 | 24,998 | Jake Peavy | Luke Hochevar | Greg Holland | Jake Peavy | Jonathan Broxton | 421 | 360 | 61 |
| 2012-07-15 | @ KCA | 88 | W 2-1 | 50-38 | 1 | 25,714 | Chris Sale | Luis Mendoza | Chris Sale | Luis Mendoza | Addison Reed | 423 | 361 | 62 |
| 2012-07-16 | @ BOS | 89 | L 1-5 | 50-39 | 1 | 38,334 | Dylan Axelrod | Aaron Cook | Vicente Padilla | Leyson Septimo | | 424 | 366 | 58 |
| 2012-07-17 | @ BOS | 90 | W 7-5 | 51-39 | 1 | 37,771 | Philip Humber | Jon Lester | Philip Humber | Jon Lester | Addison Reed | 431 | 371 | 60 |
| 2012-07-18 | @ BOS | 91 | L 1-10 | 51-40 | 1 | 37,367 | Pedro Hernandez | Felix Doubront | Felix Doubront | Pedro Hernandez | | 432 | 381 | 51 |
| 2012-07-19 | @ BOS | 92 | L 1-3 | 51-41 | 2 | 38,413 | Jose Quintana | Clay Buchholz | Alfredo Aceves | Matt Thornton | | 433 | 384 | 49 |
| 2012-07-20 | @ DET | 93 | L 2-4 | 51-42 | 2 | 44,572 | Jake Peavy | Justin Verlander | Justin Verlander | Jake Peavy | Jose Valverde | 435 | 388 | 47 |
| 2012-07-21 | @ DET | 94 | L 1-7 | 51-43 | 2 | 42,888 | Chris Sale | Rick Porcello | Rick Porcello | Chris Sale | | 436 | 395 | 41 |
| 2012-07-22 | @ DET | 95 | L 4-6 | 51-44 | 2 | 41,281 | Philip Humber | Jacob Turner | Jacob Turner | Philip Humber | Joaquin Benoit | 440 | 401 | 39 |
| 2012-07-23 | vs MIN | 96 | W 7-4 | 52-44 | 2 | 37,788 | Gavin Floyd | Francisco Liriano | Gavin Floyd | Francisco Liriano | Addison Reed | 447 | 405 | 42 |
| 2012-07-24 | vs MIN | 97 | L 11-4 | 52-45 | 2 | 34,715 | Jose Quintana | Cole De Vries | Nate Jones | Casey Fien | | 458 | 409 | 49 |
| 2012-07-25 | vs MIN | 98 | W 8-2 | 53-45 | 2 | 32,261 | Jake Peavy | Nick Blackburn | Jake Peavy | Nick Blackburn | | 466 | 411 | 55 |
| 2012-07-27 | @ TEX | 99 | W 9-5 | 54-45 | 2 | 47,638 | Chris Sale | Yu Darvish | Chris Sale | Yu Darvish | | 475 | 416 | 59 |
| 2012-07-28 | @ TEX | 100 | W 5-2 | 55-45 | 2 | 47,580 | Philip Humber | Matt Harrison | Philip Humber | Matt Harrison | | 480 | 418 | 62 |
| 2012-07-29 | @ TEX | 101 | L 0-2 | 55-46 | 2 | 46,744 | Gavin Floyd | Scott Feldman | Scott Feldman | Gavin Floyd | Joe Nathan | 480 | 420 | 60 |
| 2012-07-30 | @ MIN | 102 | L 6-7 | 55-47 | 2 | 35,018 | Jose Quintana | Cole De Vries | Glen Perkins | Brett Myers | | 486 | 427 | 59 |
| 2012-07-31 | @ MIN | 103 | W 4-3 | 56-47 | 2 | 36,424 | Francisco Liriano | Nick Blackburn | Matt Thornton | Jeff Gray | Addison Reed | 490 | 430 | 60 |
| 2012-08-01 | @ MIN | 104 | W 3-2 | 57-47 | 2 | 34,823 | Jake Peavy | Scott Diamond | Jake Peavy | Scott Diamond | Addison Reed | 493 | 432 | 61 |
| 2012-08-03 | vs ANA | 105 | W 8-6 | 58-47 | 1 | 32,060 | Philip Humber | Zack Greinke | Matt Thornton | Hisanori Takahashi | | 501 | 438 | 63 |
| 2012-08-04 | vs ANA | 106 | L 5-6 | 58-48 | 2 | 28,571 | Gavin Floyd | Ervin Santana | Kevin Jepsen | Matt Thornton | Ernesto Frieri | 506 | 444 | 62 |
| 2012-08-05 | vs ANA | 107 | W 4-2 | 59-48 | 1 | 30,202 | Francisco Liriano | Dan Haren | Nate Jones | Jason Isringhausen | Addison Reed | 510 | 446 | 64 |
| 2012-08-06 | vs KCA | 108 | W 4-2 | 60-48 | 1 | 30,097 | Chris Sale | Luis Mendoza | Chris Sale | Luis Mendoza | Addison Reed | 514 | 448 | 66 |
| 2012-08-07 | vs KCA | 109 | L 2-5 | 60-49 | 2 | 27,194 | Jake Peavy | Bruce Chen | Bruce Chen | Jake Peavy | Greg Holland | 516 | 453 | 63 |
| 2012-08-08 | vs KCA | 110 | L 1-2 | 60-50 | 2 | 25,151 | Jose Quintana | Jeremy Guthrie | Jeremy Guthrie | Jose Quintana | Greg Holland | 517 | 455 | 62 |
| 2012-08-10 | vs OAK | 111 | W 4-3 | 61-50 | 2 | 25,041 | Gavin Floyd | Brandon McCarthy | Brett Myers | Pat Neshek | | 521 | 458 | 63 |
| 2012-08-11 | vs OAK | 112 | L 7-9 | 61-51 | 2 | 26,686 | Francisco Liriano | Travis Blackley | Ryan Cook | Matt Thornton | Grant Balfour | 528 | 467 | 61 |
| 2012-08-12 | vs OAK | 113 | W 7-3 | 62-51 | 1 | 25,106 | Chris Sale | Bartolo Colon | Chris Sale | Bartolo Colon | | 535 | 470 | 65 |
| 2012-08-13 | @ TOR | 114 | L 2-3 | 62-52 | 1 | 16,828 | Jake Peavy | Carlos Villanueva | Steve Delabar | Leyson Septimo | | 537 | 473 | 64 |
| 2012-08-14 | @ TOR | 115 | W 3-2 | 63-52 | 1 | 18,919 | Jose Quintana | Henderson Alvarez | Jose Quintana | Henderson Alvarez | Addison Reed | 540 | 475 | 65 |
| 2012-08-15 | @ TOR | 116 | W 9-5 | 64-52 | 1 | 20,119 | Gavin Floyd | Ricky Romero | Gavin Floyd | Ricky Romero | | 549 | 480 | 69 |
| 2012-08-16 | @ TOR | 117 | W 7-2 | 65-52 | 1 | 19,855 | Francisco Liriano | Aaron Laffey | Francisco Liriano | Aaron Laffey | | 556 | 482 | 74 |
| 2012-08-17 | @ KCA | 118 | L 2-4 | 65-53 | 2 | 22,169 | Chris Sale | Luis Mendoza | Luis Mendoza | Chris Sale | Greg Holland | 558 | 486 | 72 |
| 2012-08-18 | @ KCA | 119 | L 4-9 | 65-54 | 2 | 23,858 | Jake Peavy | Bruce Chen | Bruce Chen | Jake Peavy | | 562 | 495 | 67 |
| 2012-08-19 | @ KCA | 120 | L 2-5 | 65-55 | 2 | 22,401 | Jose Quintana | Jeremy Guthrie | Greg Holland | Jesse Crain | | 564 | 500 | 64 |
| 2012-08-20 | vs NYA | 121 | W 9-6 | 66-55 | 1 | 27,561 | Gavin Floyd | Freddy Garcia | Brett Myers | Boone Logan | Addison Reed | 573 | 506 | 67 |
| 2012-08-21 | vs NYA | 122 | W 7-3 | 67-55 | 1 | 24,247 | Francisco Liriano | Ivan Nova | Francisco Liriano | Ivan Nova | | 580 | 509 | 71 |
| 2012-08-22 | vs NYA | 123 | W 2-1 | 68-55 | 1 | 26,319 | Chris Sale | Phil Hughes | Chris Sale | Phil Hughes | Addison Reed | 582 | 510 | 72 |
| 2012-08-24 | vs SEA | 124 | W 9-8 | 69-55 | 1 | 25,058 | Jake Peavy | Jason Vargas | Addison Reed | Tom Wilhelmsen | | 591 | 518 | 73 |
| 2012-08-25 | vs SEA | 125 | W 5-4 | 70-55 | 1 | 27,562 | Jose Quintana | Blake Beavan | Nate Jones | Blake Beavan | Addison Reed | 596 | 522 | 74 |
| 2012-08-26 | vs SEA | 126 | W 4-3 | 71-55 | 1 | 23,146 | Gavin Floyd | Kevin Millwood | Nate Jones | Kevin Millwood | | 600 | 525 | 75 |
| 2012-08-27 | @ BAL | 127 | L 3-4 | 71-56 | 1 | 10,955 | Francisco Liriano | Wei-Yin Chen | Pedro Strop | Brett Myers | Jim Johnson | 603 | 529 | 74 |
| 2012-08-28 | @ BAL | 128 | L 0-6 | 71-57 | 1 | 12,841 | Chris Sale | Chris Tillman | Chris Tillman | Chris Sale | | 603 | 535 | 68 |
| 2012-08-29 | @ BAL | 129 | W 8-1 | 72-57 | 1 | 13,098 | Dylan Axelrod | Joe Saunders | Dylan Axelrod | Joe Saunders | | 611 | 536 | 75 |
| 2012-08-30 | @ BAL | 130 | L 3-5 | 72-58 | 1 | 10,141 | Jose Quintana | Zachary Britton | Zachary Britton | Jose Quintana | Jim Johnson | 614 | 541 | 73 |
| 2012-08-31 | @ DET | 131 | L 4-7 | 72-59 | 1 | 36,721 | Jake Peavy | Doug Fister | Octavio Dotel | Jake Peavy | Jose Valverde | 618 | 548 | 70 |
| 2012-09-01 | @ DET | 132 | L 1-5 | 72-60 | 2 | 40,059 | Francisco Liriano | Max Scherzer | Max Scherzer | Francisco Liriano | | 619 | 553 | 66 |
| 2012-09-02 | @ DET | 133 | L 2-4 | 72-61 | 2 | 42,192 | Chris Sale | Justin Verlander | Justin Verlander | Chris Sale | Jose Valverde | 621 | 557 | 64 |
| 2012-09-03 | vs MIN | 134 | W 4-2 | 73-61 | 2 | 21,676 | Hector Santiago | Samuel Deduno | Hector Santiago | Samuel Deduno | Addison Reed | 625 | 559 | 66 |
| 2012-09-04 | vs MIN | 135 | W 9-18 | 74-61 | 1 | 15,698 | Jose Quintana | Scott Diamond | Scott Diamond | Jose Quintana | | 634 | 577 | 57 |
| 2012-09-05 | vs MIN | 136 | W 6-2 | 75-61 | 1 | 17,336 | Jake Peavy | P.J. Walters | Jake Peavy | P.J. Walters | | 640 | 579 | 61 |
| 2012-09-07 | vs KCA | 137 | L 5-7 | 75-62 | 1 | 26,660 | Francisco Liriano | Luis Mendoza | Kelvin Herrera | Addison Reed | Greg Holland | 645 | 586 | 59 |
| 2012-09-08 | vs KCA | 138 | W 5-4 | 76-62 | 1 | 26,227 | Chris Sale | Bruce Chen | Chris Sale | Bruce Chen | Addison Reed | 650 | 590 | 60 |
| 2012-09-09 | vs KCA | 139 | L 1-2 | 76-63 | 1 | 19,356 | Hector Santiago | Jeremy Guthrie | Kelvin Herrera | Brett Myers | Greg Holland | 651 | 592 | 59 |
| 2012-09-10 | vs DET | 140 | W 6-1 | 77-63 | 1 | 30,287 | Jose Quintana | Rick Porcello | Jose Quintana | Rick Porcello | | 657 | 593 | 64 |
| 2012-09-11 | vs DET | 141 | L 3-5 | 77-64 | 1 | 26,504 | Jake Peavy | Doug Fister | Doug Fister | Jake Peavy | Jose Valverde | 660 | 598 | 62 |
| 2012-09-12 | vs DET | 142 | L 6-8 | 77-65 | 1 | 30,667 | Gavin Floyd | Max Scherzer | Max Scherzer | Gavin Floyd | Jose Valverde | 666 | 606 | 60 |
| 2012-09-14 | @ MIN | 143 | W 6-0 | 78-65 | 1 | 30,729 | Chris Sale | Esmerling Vasquez | Chris Sale | Esmerling Vasquez | | 672 | 606 | 66 |
| 2012-09-15 | @ MIN | 144 | W 5-3 | 79-65 | 1 | 36,308 | Francisco Liriano | Samuel Deduno | Francisco Liriano | Samuel Deduno | Matt Thornton | 677 | 609 | 68 |
| 2012-09-16 | @ MIN | 145 | W 9-2 | 80-65 | 1 | 31,722 | Jake Peavy | Scott Diamond | Jake Peavy | Scott Diamond | | 686 | 611 | 75 |
| 2012-09-17 | vs DET | 146 | W 5-4 | 81-65 | 1 | 29,130 | Jose Quintana | Doug Fister | Nate Jones | Doug Fister | Addison Reed | 691 | 615 | 76 |
| 2012-09-18 | @ KCA | 147 | W 3-2 | 82-65 | 1 | 14,420 | Gavin Floyd | Luke Hochevar | Gavin Floyd | Luke Hochevar | Addison Reed | 694 | 617 | 77 |
| 2012-09-19 | @ KCA | 148 | L 0-3 | 82-66 | 1 | 15,120 | Chris Sale | Bruce Chen | Bruce Chen | Chris Sale | Greg Holland | 694 | 620 | 74 |
| 2012-09-20 | @ KCA | 149 | L 3-4 | 82-67 | 1 | 14,710 | Francisco Liriano | Jeremy Guthrie | Greg Holland | Jesse Crain | | 697 | 624 | 73 |
| 2012-09-21 | @ ANA | 150 | L 2-6 | 82-68 | 1 | 39,326 | Jake Peavy | Ervin Santana | Ervin Santana | Jake Peavy | | 699 | 630 | 69 |
| 2012-09-22 | @ ANA | 151 | L 2-4 | 82-69 | 2 | 41,440 | Jose Quintana | Dan Haren | Dan Haren | Jose Quintana | Ernesto Frieri | 701 | 634 | 67 |
| 2012-09-23 | @ ANA | 152 | L 1-4 | 82-70 | 3 | 36,546 | Gavin Floyd | Jered Weaver | Jered Weaver | Gavin Floyd | | 702 | 638 | 64 |
| 2012-09-24 | vs CLE | 153 | W 5-4 | 83-70 | 2 | 20,206 | Chris Sale | Zach McAllister | Brett Myers | Vinnie Pestano | Donald Veal | 707 | 642 | 65 |
| 2012-09-25 | vs CLE | 154 | L 3-4 | 83-71 | 2 | 13,797 | Francisco Liriano | Corey Kluber | Corey Kluber | Francisco Liriano | Chris Perez | 710 | 646 | 64 |
| 2012-09-26 | vs CLE | 155 | L 4-6 | 83-72 | 2 | 20,166 | Hector Santiago | Justin Masterson | Tony Sipp | Matt Thornton | Chris Perez | 714 | 652 | 62 |
| 2012-09-27 | vs TBA | 156 | L 2-3 | 83-73 | 2 | 18,630 | Jake Peavy | James Shields | Joel Peralta | Brett Myers | Fernando Rodney | 716 | 655 | 61 |
| 2012-09-28 | vs TBA | 157 | W 3-1 | 84-73 | 2 | 25,264 | Gavin Floyd | Jeremy Hellickson | Gavin Floyd | Jeremy Hellickson | Addison Reed | 719 | 656 | 63 |
| 2012-09-29 | vs TBA | 158 | W 4-10 | 85-73 | 2 | 26,559 | Chris Sale | Matt Moore | Matt Moore | Chris Sale | | 723 | 666 | 57 |
| 2012-09-30 | vs TBA | 159 | L 2-6 | 85-74 | 2 | 26,831 | Jose Quintana | David Price | David Price | Jose Quintana | | 725 | 672 | 53 |
| 2012-10-01 | @ CLE | 160 | W 11-0 | 86-74 | 2 | 14,756 | Hector Santiago | Corey Kluber | Hector Santiago | Corey Kluber | | 736 | 672 | 64 |
| 2012-10-02 | @ CLE | 161 | L 3-4 | 86-75 | 2 | 10,015 | Jake Peavy | Justin Masterson | Chris Seddon | Matt Thornton | | 739 | 676 | 63 |
| 2012-10-03 | @ CLE | 162 | W 9-0 | 87-75 | 2 | 18,093 | Gavin Floyd | David Huff | Gavin Floyd | David Huff | | 748 | 676 | 72 |