| 2012-04-05 | @ DET | 1 | L 2-3 | 0-1 | 2 | 45,027 | Jon Lester | Justin Verlander | Jose Valverde | Mark Melancon | | 2 | 3 | -1 |
| 2012-04-07 | @ DET | 2 | L 0-10 | 0-2 | 4 | 44,710 | Josh Beckett | Doug Fister | Duane Below | Josh Beckett | | 2 | 13 | -11 |
| 2012-04-08 | @ DET | 3 | L 12-13 | 0-3 | 4 | 30,788 | Clay Buchholz | Max Scherzer | Duane Below | Mark Melancon | | 14 | 26 | -12 |
| 2012-04-09 | @ TOR | 4 | W 4-2 | 1-3 | 4 | 48,473 | Felix Doubront | Henderson Alvarez | Scott Atchison | Sergio Santos | Alfredo Aceves | 18 | 28 | -10 |
| 2012-04-10 | @ TOR | 5 | L 3-7 | 1-4 | 5 | 26,351 | Daniel Bard | Kyle Drabek | Kyle Drabek | Daniel Bard | | 21 | 35 | -14 |
| 2012-04-11 | @ TOR | 6 | L 1-3 | 1-5 | 5 | 25,285 | Jon Lester | Ricky Romero | Ricky Romero | Jon Lester | Sergio Santos | 22 | 38 | -16 |
| 2012-04-13 | vs TBA | 7 | L 12-2 | 1-6 | 5 | 37,032 | Josh Beckett | David Price | Josh Beckett | David Price | | 34 | 40 | -6 |
| 2012-04-14 | vs TBA | 8 | L 13-5 | 1-7 | 5 | 38,024 | Clay Buchholz | Jeremy Hellickson | Clay Buchholz | Burke Badenhop | | 47 | 45 | 2 |
| 2012-04-15 | vs TBA | 9 | W 6-4 | 2-7 | 5 | 38,024 | Felix Doubront | Matt Moore | Vicente Padilla | Matt Moore | Alfredo Aceves | 53 | 49 | 4 |
| 2012-04-16 | vs TBA | 10 | L 0-1 | 2-8 | 5 | 38,108 | Daniel Bard | James Shields | James Shields | Daniel Bard | Fernando Rodney | 53 | 50 | 3 |
| 2012-04-17 | vs TEX | 11 | W 3-18 | 3-8 | 5 | 38,229 | Jon Lester | Colby Lewis | Colby Lewis | Jon Lester | | 56 | 68 | -12 |
| 2012-04-18 | vs TEX | 12 | L 3-6 | 3-9 | 5 | 37,967 | Josh Beckett | Derek Holland | Derek Holland | Josh Beckett | | 59 | 74 | -15 |
| 2012-04-20 | vs NYA | 13 | L 2-6 | 3-10 | 5 | 36,770 | Clay Buchholz | Ivan Nova | Ivan Nova | Clay Buchholz | | 61 | 80 | -19 |
| 2012-04-21 | vs NYA | 14 | W 9-15 | 4-10 | 5 | 37,839 | Felix Doubront | Freddy Garcia | Rafael Soriano | Alfredo Aceves | | 70 | 95 | -25 |
| 2012-04-23 | @ MIN | 15 | W 6-5 | 5-10 | 5 | 32,351 | Jon Lester | Jason Marquis | Daniel Bard | Matt Capps | Alfredo Aceves | 76 | 100 | -24 |
| 2012-04-24 | @ MIN | 16 | L 11-2 | 5-11 | 5 | 33,651 | Josh Beckett | Nick Blackburn | Josh Beckett | Nick Blackburn | | 87 | 102 | -15 |
| 2012-04-25 | @ MIN | 17 | W 7-6 | 6-11 | 5 | 32,254 | Clay Buchholz | Liam Hendriks | Clay Buchholz | Liam Hendriks | Alfredo Aceves | 94 | 108 | -14 |
| 2012-04-26 | @ CHA | 18 | L 10-3 | 6-12 | 5 | 20,266 | Felix Doubront | Philip Humber | Felix Doubront | Philip Humber | Junichi Tazawa | 104 | 111 | -7 |
| 2012-04-27 | @ CHA | 19 | L 10-3 | 6-13 | 5 | 20,414 | Daniel Bard | John Danks | Daniel Bard | John Danks | | 114 | 114 | 0 |
| 2012-04-28 | @ CHA | 20 | W 1-0 | 7-13 | 5 | 20,057 | Jon Lester | Jake Peavy | Jon Lester | Jake Peavy | Alfredo Aceves | 115 | 114 | 1 |
| 2012-04-29 | @ CHA | 21 | L 1-4 | 7-14 | 5 | 22,811 | Josh Beckett | Gavin Floyd | Gavin Floyd | Josh Beckett | Matt Thornton | 116 | 118 | -2 |
| 2012-04-30 | vs OAK | 22 | L 11-6 | 7-15 | 5 | 37,359 | Clay Buchholz | Tom Milone | Clay Buchholz | Tom Milone | | 127 | 124 | 3 |
| 2012-05-01 | vs OAK | 23 | L 3-5 | 7-16 | 5 | 37,225 | Felix Doubront | Jarrod Parker | Jarrod Parker | Felix Doubront | Jordan Norberto | 130 | 129 | 1 |
| 2012-05-02 | vs OAK | 24 | L 2-4 | 7-17 | 5 | 37,434 | Daniel Bard | Brandon McCarthy | Brandon McCarthy | Daniel Bard | Brian Fuentes | 132 | 133 | -1 |
| 2012-05-04 | vs BAL | 25 | L 4-6 | 7-18 | 5 | 37,223 | Jon Lester | Wei-Yin Chen | Troy Patton | Franklin Morales | Jim Johnson | 136 | 139 | -3 |
| 2012-05-05 | vs BAL | 26 | L 2-8 | 7-19 | 5 | 37,581 | Aaron Cook | Jason Hammel | Jason Hammel | Aaron Cook | | 138 | 147 | -9 |
| 2012-05-06 | vs BAL | 27 | L 6-9 | 7-20 | 5 | 37,394 | Clay Buchholz | Tommy Hunter | Chris Davis | Darnell McDonald | | 144 | 156 | -12 |
| 2012-05-07 | @ KCA | 28 | L 11-5 | 7-21 | 5 | 19,502 | Felix Doubront | Jonathan Sanchez | Felix Doubront | Jonathan Sanchez | Vicente Padilla | 155 | 161 | -6 |
| 2012-05-08 | @ KCA | 29 | L 4-6 | 7-22 | 5 | 20,524 | Daniel Bard | Danny Duffy | Jose Mijares | Daniel Bard | Jonathan Broxton | 159 | 167 | -8 |
| 2012-05-09 | @ KCA | 30 | L 3-4 | 7-23 | 5 | 18,339 | Jon Lester | Bruce Chen | Bruce Chen | Jon Lester | Jonathan Broxton | 162 | 171 | -9 |
| 2012-05-10 | vs CLE | 31 | L 3-8 | 7-24 | 6 | 37,348 | Josh Beckett | Derek Lowe | Derek Lowe | Josh Beckett | | 165 | 179 | -14 |
| 2012-05-11 | vs CLE | 32 | W 7-5 | 8-24 | 5 | 37,438 | Clay Buchholz | Ubaldo Jimenez | Clay Buchholz | Ubaldo Jimenez | Alfredo Aceves | 172 | 184 | -12 |
| 2012-05-12 | vs CLE | 33 | W 4-1 | 9-24 | 5 | 38,048 | Felix Doubront | Zach McAllister | Felix Doubront | Zach McAllister | Alfredo Aceves | 176 | 185 | -9 |
| 2012-05-13 | vs CLE | 34 | W 12-1 | 10-24 | 5 | 37,611 | Daniel Bard | Justin Masterson | Daniel Bard | Justin Masterson | | 188 | 186 | 2 |
| 2012-05-14 | vs SEA | 35 | W 6-1 | 11-24 | 5 | 37,334 | Jon Lester | Jason Vargas | Jon Lester | Jason Vargas | | 194 | 187 | 7 |
| 2012-05-15 | vs SEA | 36 | W 5-0 | 12-24 | 5 | 37,292 | Josh Beckett | Blake Beavan | Josh Beckett | Blake Beavan | | 199 | 187 | 12 |
| 2012-05-16 | @ TBA | 37 | L 1-2 | 12-25 | 5 | 20,843 | Clay Buchholz | Jeremy Hellickson | Jeremy Hellickson | Clay Buchholz | Fernando Rodney | 200 | 189 | 11 |
| 2012-05-17 | @ TBA | 38 | W 5-3 | 13-25 | 5 | 19,842 | Felix Doubront | Matt Moore | Felix Doubront | Matt Moore | Alfredo Aceves | 205 | 192 | 13 |
| 2012-05-18 | @ PHI | 39 | L 4-6 | 13-26 | 5 | 45,205 | Daniel Bard | Cole Hamels | Cole Hamels | Daniel Bard | Jonathan Papelbon | 209 | 198 | 11 |
| 2012-05-19 | @ PHI | 40 | W 7-5 | 14-26 | 5 | 45,656 | Jon Lester | Joe Blanton | Jon Lester | Joe Blanton | Alfredo Aceves | 216 | 203 | 13 |
| 2012-05-20 | @ PHI | 41 | W 5-1 | 15-26 | 5 | 45,586 | Josh Beckett | Cliff Lee | Josh Beckett | Cliff Lee | | 221 | 204 | 17 |
| 2012-05-21 | @ BAL | 42 | W 8-6 | 16-26 | 5 | 16,392 | Clay Buchholz | Tommy Hunter | Andrew Miller | Kevin Gregg | Alfredo Aceves | 229 | 210 | 19 |
| 2012-05-22 | @ BAL | 43 | L 1-4 | 16-27 | 5 | 25,171 | Felix Doubront | Brian Matusz | Brian Matusz | Felix Doubront | Jim Johnson | 230 | 214 | 16 |
| 2012-05-23 | @ BAL | 44 | W 6-5 | 17-27 | 5 | 27,806 | Daniel Bard | Jake Arrieta | Daniel Bard | Jake Arrieta | Alfredo Aceves | 236 | 219 | 17 |
| 2012-05-25 | vs TBA | 45 | L 4-7 | 17-28 | 5 | 37,594 | Jon Lester | Alex Cobb | Alex Cobb | Jon Lester | Fernando Rodney | 240 | 226 | 14 |
| 2012-05-26 | vs TBA | 46 | W 3-2 | 18-28 | 5 | 38,099 | Josh Beckett | David Price | Rich Hill | Fernando Rodney | | 243 | 228 | 15 |
| 2012-05-27 | vs TBA | 47 | L 3-4 | 18-29 | 5 | 37,844 | Clay Buchholz | Jeremy Hellickson | Jake McGee | Alfredo Aceves | Fernando Rodney | 246 | 232 | 14 |
| 2012-05-28 | vs DET | 48 | W 7-4 | 19-29 | 5 | 37,921 | Felix Doubront | Doug Fister | Felix Doubront | Doug Fister | | 253 | 236 | 17 |
| 2012-05-29 | vs DET | 49 | W 6-3 | 20-29 | 5 | 37,216 | Daniel Bard | Justin Verlander | Daniel Bard | Justin Verlander | Alfredo Aceves | 259 | 239 | 20 |
| 2012-05-30 | vs DET | 50 | W 6-4 | 21-29 | 5 | 37,195 | Jon Lester | Drew Smyly | Matt Albers | Octavio Dotel | Alfredo Aceves | 265 | 243 | 22 |
| 2012-05-31 | vs DET | 51 | L 3-7 | 21-30 | 5 | 37,629 | Josh Beckett | Max Scherzer | Max Scherzer | Josh Beckett | | 268 | 250 | 18 |
| 2012-06-01 | @ TOR | 52 | W 7-2 | 22-30 | 5 | 29,678 | Clay Buchholz | Henderson Alvarez | Clay Buchholz | Henderson Alvarez | | 275 | 252 | 23 |
| 2012-06-02 | @ TOR | 53 | W 7-4 | 23-30 | 5 | 43,390 | Felix Doubront | Kyle Drabek | Felix Doubront | Kyle Drabek | Alfredo Aceves | 282 | 256 | 26 |
| 2012-06-03 | @ TOR | 54 | L 1-5 | 23-31 | 5 | 41,925 | Daniel Bard | Drew Hutchison | Drew Hutchison | Daniel Bard | | 283 | 261 | 22 |
| 2012-06-05 | vs BAL | 55 | L 6-8 | 23-32 | 5 | 37,181 | Jon Lester | Jason Hammel | Jim Johnson | Alfredo Aceves | | 289 | 269 | 20 |
| 2012-06-06 | vs BAL | 56 | L 1-2 | 23-33 | 5 | 37,243 | Josh Beckett | Wei-Yin Chen | Wei-Yin Chen | Josh Beckett | Jim Johnson | 290 | 271 | 19 |
| 2012-06-07 | vs BAL | 57 | W 7-0 | 24-33 | 5 | 37,307 | Clay Buchholz | Brian Matusz | Clay Buchholz | Brian Matusz | | 297 | 271 | 26 |
| 2012-06-08 | vs WAS | 58 | L 4-7 | 24-34 | 5 | 37,309 | Felix Doubront | Stephen Strasburg | Stephen Strasburg | Felix Doubront | Tyler Clippard | 301 | 278 | 23 |
| 2012-06-09 | vs WAS | 59 | L 2-4 | 24-35 | 5 | 37,534 | Daisuke Matsuzaka | Gio Gonzalez | Gio Gonzalez | Daisuke Matsuzaka | Tyler Clippard | 303 | 282 | 21 |
| 2012-06-10 | vs WAS | 60 | L 3-4 | 24-36 | 5 | 37,467 | Jon Lester | Jordan Zimmermann | Tom Gorzelanny | Alfredo Aceves | Tyler Clippard | 306 | 286 | 20 |
| 2012-06-11 | @ MIA | 61 | L 1-4 | 24-37 | 5 | 32,562 | Josh Beckett | Josh Johnson | Josh Johnson | Josh Beckett | Heath Bell | 307 | 290 | 17 |
| 2012-06-12 | @ MIA | 62 | W 2-1 | 25-37 | 5 | 29,326 | Clay Buchholz | Mark Buehrle | Clay Buchholz | Mark Buehrle | Alfredo Aceves | 309 | 291 | 18 |
| 2012-06-13 | @ MIA | 63 | L 10-2 | 25-38 | 5 | 33,119 | Felix Doubront | Ricky Nolasco | Felix Doubront | Ricky Nolasco | | 319 | 293 | 26 |
| 2012-06-15 | @ CHN | 64 | L 0-3 | 25-39 | 5 | 40,073 | Daisuke Matsuzaka | Ryan Dempster | Ryan Dempster | Daisuke Matsuzaka | Carlos Marmol | 319 | 296 | 23 |
| 2012-06-16 | @ CHN | 65 | W 4-3 | 26-39 | 5 | 40,766 | Jon Lester | Jeff Samardzija | Jon Lester | Jeff Samardzija | Alfredo Aceves | 323 | 299 | 24 |
| 2012-06-17 | @ CHN | 66 | W 7-4 | 27-39 | 5 | 38,531 | Franklin Morales | Paul Maholm | Matt Albers | Shawn Camp | | 330 | 303 | 27 |
| 2012-06-19 | vs MIA | 67 | W 7-5 | 28-39 | 5 | 37,701 | Clay Buchholz | Mark Buehrle | Clay Buchholz | Mark Buehrle | Alfredo Aceves | 337 | 308 | 29 |
| 2012-06-20 | vs MIA | 68 | L 15-5 | 28-40 | 5 | 37,362 | Felix Doubront | Ricky Nolasco | Felix Doubront | Ricky Nolasco | | 352 | 313 | 39 |
| 2012-06-21 | vs MIA | 69 | W 6-5 | 29-40 | 5 | 37,261 | Daisuke Matsuzaka | Carlos Zambrano | Scott Atchison | Edward Mujica | Alfredo Aceves | 358 | 318 | 40 |
| 2012-06-22 | vs ATL | 70 | L 1-4 | 29-41 | 5 | 37,281 | Jon Lester | Jair Jurrjens | Jair Jurrjens | Jon Lester | Craig Kimbrel | 359 | 322 | 37 |
| 2012-06-23 | vs ATL | 71 | W 8-4 | 30-41 | 5 | 37,782 | Franklin Morales | Randall Delgado | Franklin Morales | Randall Delgado | | 367 | 326 | 41 |
| 2012-06-24 | vs ATL | 72 | W 9-4 | 31-41 | 6 | 37,565 | Aaron Cook | Mike Minor | Aaron Cook | Mike Minor | | 376 | 330 | 46 |
| 2012-06-25 | vs TOR | 73 | L 6-9 | 31-42 | 5 | 37,208 | Felix Doubront | Henderson Alvarez | Henderson Alvarez | Felix Doubront | Casey Janssen | 382 | 339 | 43 |
| 2012-06-26 | vs TOR | 74 | W 5-1 | 32-42 | 5 | 37,755 | Daisuke Matsuzaka | Aaron Laffey | Andrew Miller | Luis Perez | | 387 | 340 | 47 |
| 2012-06-27 | vs TOR | 75 | L 10-4 | 32-43 | 5 | 37,744 | Jon Lester | Ricky Romero | Jon Lester | Ricky Romero | | 397 | 344 | 53 |
| 2012-06-28 | @ SEA | 76 | L 0-1 | 32-44 | 5 | 20,692 | Franklin Morales | Felix Hernandez | Felix Hernandez | Scott Atchison | | 397 | 345 | 52 |
| 2012-06-29 | @ SEA | 77 | W 5-0 | 33-44 | 5 | 23,094 | Aaron Cook | Hector Noesi | Aaron Cook | Hector Noesi | | 402 | 345 | 57 |
| 2012-06-30 | @ SEA | 78 | L 2-3 | 33-45 | 5 | 31,311 | Josh Beckett | Erasmo Ramirez | Shawn Kelley | Alfredo Aceves | | 404 | 348 | 56 |
| 2012-07-01 | @ SEA | 79 | W 2-1 | 34-45 | 5 | 34,065 | Felix Doubront | Jason Vargas | Vicente Padilla | Brandon League | Alfredo Aceves | 406 | 349 | 57 |
| 2012-07-02 | @ OAK | 80 | L 1-6 | 34-46 | 5 | 17,434 | Daisuke Matsuzaka | Jarrod Parker | Jarrod Parker | Daisuke Matsuzaka | | 407 | 355 | 52 |
| 2012-07-03 | @ OAK | 81 | L 2-3 | 34-47 | 5 | 35,067 | Jon Lester | Bartolo Colon | Jerry Blevins | Alfredo Aceves | | 409 | 358 | 51 |
| 2012-07-04 | @ OAK | 82 | L 2-3 | 34-48 | 5 | 28,240 | Aaron Cook | A.J. Griffin | Grant Balfour | Aaron Cook | Ryan Cook | 411 | 361 | 50 |
| 2012-07-06 | vs NYA | 83 | W 8-10 | 35-48 | 5 | 38,066 | Josh Beckett | Hiroki Kuroda | Boone Logan | Andrew Miller | Rafael Soriano | 419 | 371 | 48 |
| 2012-07-07 | vs NYA | 84 | L 1-6 | 35-49 | 7 | 38,170 | Franklin Morales | Freddy Garcia | Freddy Garcia | Franklin Morales | | 420 | 377 | 43 |
| 2012-07-07 | vs NYA | 85 | W 9-5 | 35-49 | 7 | 37,791 | Felix Doubront | Phil Hughes | Felix Doubront | Phil Hughes | | 429 | 382 | 47 |
| 2012-07-08 | vs NYA | 86 | L 3-7 | 36-50 | 5 | 38,270 | Jon Lester | Ivan Nova | Ivan Nova | Jon Lester | | 432 | 389 | 43 |
| 2012-07-13 | @ TBA | 87 | W 3-1 | 37-50 | 5 | 29,089 | Franklin Morales | Jeremy Hellickson | Franklin Morales | Jeremy Hellickson | Alfredo Aceves | 435 | 390 | 45 |
| 2012-07-14 | @ TBA | 88 | L 3-5 | 37-51 | 5 | 27,311 | Clay Buchholz | David Price | David Price | Clay Buchholz | Fernando Rodney | 438 | 395 | 43 |
| 2012-07-15 | @ TBA | 89 | W 7-3 | 38-51 | 5 | 26,131 | Josh Beckett | James Shields | Josh Beckett | James Shields | | 445 | 398 | 47 |
| 2012-07-16 | vs CHA | 90 | W 5-1 | 39-51 | 5 | 38,334 | Aaron Cook | Dylan Axelrod | Vicente Padilla | Leyson Septimo | | 450 | 399 | 51 |
| 2012-07-17 | vs CHA | 91 | L 5-7 | 39-52 | 5 | 37,771 | Jon Lester | Philip Humber | Philip Humber | Jon Lester | Addison Reed | 455 | 406 | 49 |
| 2012-07-18 | vs CHA | 92 | W 10-1 | 40-52 | 5 | 37,367 | Felix Doubront | Pedro Hernandez | Felix Doubront | Pedro Hernandez | | 465 | 407 | 58 |
| 2012-07-19 | vs CHA | 93 | W 3-1 | 41-52 | 5 | 38,413 | Clay Buchholz | Jose Quintana | Alfredo Aceves | Matt Thornton | | 468 | 408 | 60 |
| 2012-07-20 | vs TOR | 94 | L 1-6 | 41-53 | 5 | 38,093 | Josh Beckett | Aaron Laffey | Aaron Laffey | Josh Beckett | | 469 | 414 | 55 |
| 2012-07-21 | vs TOR | 95 | L 3-7 | 41-54 | 5 | 38,170 | Aaron Cook | Carlos Villanueva | Carlos Villanueva | Aaron Cook | | 472 | 421 | 51 |
| 2012-07-22 | vs TOR | 96 | W 7-15 | 42-54 | 5 | 37,737 | Jon Lester | Henderson Alvarez | Henderson Alvarez | Jon Lester | | 479 | 436 | 43 |
| 2012-07-23 | @ TEX | 97 | L 1-9 | 42-55 | 5 | 44,132 | Felix Doubront | Scott Feldman | Scott Feldman | Felix Doubront | | 480 | 445 | 35 |
| 2012-07-24 | @ TEX | 98 | W 2-1 | 43-55 | 5 | 41,237 | Clay Buchholz | Martin Perez | Vicente Padilla | Joe Nathan | Alfredo Aceves | 482 | 446 | 36 |
| 2012-07-25 | @ TEX | 99 | L 3-5 | 43-56 | 5 | 44,104 | Josh Beckett | Derek Holland | Derek Holland | Josh Beckett | Joe Nathan | 485 | 451 | 34 |
| 2012-07-27 | @ NYA | 100 | W 3-10 | 44-56 | 5 | 49,571 | Aaron Cook | Phil Hughes | Phil Hughes | Aaron Cook | | 488 | 461 | 27 |
| 2012-07-28 | @ NYA | 101 | W 8-6 | 45-56 | 5 | 49,573 | Jon Lester | CC Sabathia | Andrew Miller | Rafael Soriano | Alfredo Aceves | 496 | 467 | 29 |
| 2012-07-29 | @ NYA | 102 | W 3-2 | 46-56 | 5 | 48,526 | Felix Doubront | Hiroki Kuroda | Alfredo Aceves | David Robertson | | 499 | 469 | 30 |
| 2012-07-30 | vs DET | 103 | W 7-3 | 47-56 | 5 | 37,784 | Clay Buchholz | Max Scherzer | Clay Buchholz | Max Scherzer | | 506 | 472 | 34 |
| 2012-07-31 | vs DET | 104 | W 4-1 | 48-56 | 4 | 37,275 | Josh Beckett | Justin Verlander | Clayton Mortensen | Justin Verlander | Franklin Morales | 510 | 473 | 37 |
| 2012-08-01 | vs DET | 105 | L 5-7 | 48-57 | 4 | 37,213 | Aaron Cook | Rick Porcello | Rick Porcello | Aaron Cook | Jose Valverde | 515 | 480 | 35 |
| 2012-08-02 | vs MIN | 106 | L 0-5 | 48-58 | 4 | 37,191 | Jon Lester | Samuel Deduno | Samuel Deduno | Jon Lester | Glen Perkins | 515 | 485 | 30 |
| 2012-08-03 | vs MIN | 107 | L 5-6 | 48-59 | 4 | 37,285 | Felix Doubront | Brian Duensing | Jeff Gray | Vicente Padilla | Jared Burton | 520 | 491 | 29 |
| 2012-08-04 | vs MIN | 108 | L 4-6 | 48-60 | 5 | 37,914 | Clay Buchholz | Cole De Vries | Alex Burnett | Alfredo Aceves | Jared Burton | 524 | 497 | 27 |
| 2012-08-05 | vs MIN | 109 | W 6-4 | 49-60 | 5 | 37,019 | Franklin Morales | Nick Blackburn | Franklin Morales | Nick Blackburn | Alfredo Aceves | 530 | 501 | 29 |
| 2012-08-06 | vs TEX | 110 | W 9-2 | 50-60 | 4 | 37,316 | Aaron Cook | Yu Darvish | Aaron Cook | Yu Darvish | | 539 | 503 | 36 |
| 2012-08-07 | vs TEX | 111 | L 3-6 | 50-61 | 4 | 38,416 | Jon Lester | Ryan Dempster | Ryan Dempster | Jon Lester | Joe Nathan | 542 | 509 | 33 |
| 2012-08-08 | vs TEX | 112 | W 9-10 | 51-61 | 4 | 37,716 | Josh Beckett | Matt Harrison | Alexi Ogando | Clayton Mortensen | Joe Nathan | 551 | 519 | 32 |
| 2012-08-09 | @ CLE | 113 | L 3-5 | 51-62 | 4 | 19,639 | Felix Doubront | Ubaldo Jimenez | Ubaldo Jimenez | Felix Doubront | Chris Perez | 554 | 524 | 30 |
| 2012-08-10 | @ CLE | 114 | W 3-2 | 52-62 | 4 | 27,246 | Clay Buchholz | Chris Seddon | Clay Buchholz | Chris Seddon | | 557 | 526 | 31 |
| 2012-08-11 | @ CLE | 115 | L 2-5 | 52-63 | 4 | 27,894 | Franklin Morales | Zach McAllister | Zach McAllister | Franklin Morales | Chris Perez | 559 | 531 | 28 |
| 2012-08-12 | @ CLE | 116 | W 14-1 | 53-63 | 4 | 27,488 | Jon Lester | Corey Kluber | Jon Lester | Corey Kluber | | 573 | 532 | 41 |
| 2012-08-14 | @ BAL | 117 | L 1-7 | 53-64 | 4 | 26,204 | Josh Beckett | Wei-Yin Chen | Wei-Yin Chen | Josh Beckett | | 574 | 539 | 35 |
| 2012-08-15 | @ BAL | 118 | L 3-5 | 53-65 | 4 | 22,269 | Aaron Cook | Miguel Gonzalez | Miguel Gonzalez | Aaron Cook | Jim Johnson | 577 | 544 | 33 |
| 2012-08-16 | @ BAL | 119 | W 6-3 | 54-65 | 4 | 25,483 | Clay Buchholz | Chris Tillman | Clay Buchholz | Luis Ayala | Alfredo Aceves | 583 | 547 | 36 |
| 2012-08-17 | @ NYA | 120 | L 4-6 | 54-66 | 4 | 49,422 | Franklin Morales | Phil Hughes | Phil Hughes | Franklin Morales | Rafael Soriano | 587 | 553 | 34 |
| 2012-08-18 | @ NYA | 121 | W 4-1 | 55-66 | 4 | 49,466 | Jon Lester | David Phelps | Jon Lester | David Phelps | Alfredo Aceves | 591 | 554 | 37 |
| 2012-08-19 | @ NYA | 122 | L 1-4 | 55-67 | 4 | 48,620 | Josh Beckett | Hiroki Kuroda | Hiroki Kuroda | Josh Beckett | Rafael Soriano | 592 | 558 | 34 |
| 2012-08-21 | vs ANA | 123 | L 3-5 | 55-68 | 4 | 37,794 | Aaron Cook | Ervin Santana | Ervin Santana | Aaron Cook | Ernesto Frieri | 595 | 563 | 32 |
| 2012-08-22 | vs ANA | 124 | L 3-7 | 55-69 | 4 | 37,373 | Clay Buchholz | Jered Weaver | Jered Weaver | Clay Buchholz | | 598 | 570 | 28 |
| 2012-08-23 | vs ANA | 125 | L 13-14 | 55-70 | 4 | 37,829 | Franklin Morales | C.J. Wilson | Ernesto Frieri | Alfredo Aceves | | 611 | 584 | 27 |
| 2012-08-24 | vs KCA | 126 | W 4-3 | 56-70 | 4 | 37,228 | Jon Lester | Bruce Chen | Jon Lester | Kelvin Herrera | Andrew Bailey | 615 | 587 | 28 |
| 2012-08-25 | vs KCA | 127 | W 9-10 | 57-70 | 4 | 37,103 | Aaron Cook | Jeremy Guthrie | Francisley Bueno | Junichi Tazawa | Greg Holland | 624 | 597 | 27 |
| 2012-08-26 | vs KCA | 128 | W 8-6 | 58-70 | 4 | 37,188 | Felix Doubront | Will Smith | Pedro Beato | Will Smith | Mark Melancon | 632 | 603 | 29 |
| 2012-08-27 | vs KCA | 129 | W 5-1 | 59-70 | 4 | 37,506 | Daisuke Matsuzaka | Luke Hochevar | Daisuke Matsuzaka | Luke Hochevar | | 637 | 604 | 33 |
| 2012-08-28 | @ ANA | 130 | L 5-6 | 59-71 | 4 | 38,745 | Clay Buchholz | Jered Weaver | Kevin Jepsen | Alfredo Aceves | | 642 | 610 | 32 |
| 2012-08-29 | @ ANA | 131 | W 3-10 | 60-71 | 4 | 37,841 | Zach Stewart | C.J. Wilson | C.J. Wilson | Zach Stewart | | 645 | 620 | 25 |
| 2012-08-30 | @ ANA | 132 | L 2-5 | 60-72 | 4 | 39,013 | Jon Lester | Zack Greinke | Zack Greinke | Jon Lester | Ernesto Frieri | 647 | 625 | 22 |
| 2012-08-31 | @ OAK | 133 | L 2-20 | 60-73 | 4 | 20,121 | Aaron Cook | Brandon McCarthy | Brandon McCarthy | Aaron Cook | | 649 | 645 | 4 |
| 2012-09-01 | @ OAK | 134 | L 1-7 | 60-74 | 4 | 20,315 | Felix Doubront | A.J. Griffin | A.J. Griffin | Felix Doubront | | 650 | 652 | -2 |
| 2012-09-02 | @ OAK | 135 | L 2-6 | 60-75 | 4 | 25,314 | Daisuke Matsuzaka | Brett Anderson | Brett Anderson | Daisuke Matsuzaka | | 652 | 658 | -6 |
| 2012-09-03 | @ SEA | 136 | L 1-4 | 60-76 | 4 | 21,641 | Clay Buchholz | Jason Vargas | Jason Vargas | Clay Buchholz | Tom Wilhelmsen | 653 | 662 | -9 |
| 2012-09-04 | @ SEA | 137 | W 4-3 | 61-76 | 4 | 12,754 | Jon Lester | Blake Beavan | Jon Lester | Blake Beavan | Andrew Bailey | 657 | 665 | -8 |
| 2012-09-05 | @ SEA | 138 | L 1-2 | 61-77 | 4 | 13,037 | Aaron Cook | Kevin Millwood | Kevin Millwood | Aaron Cook | Tom Wilhelmsen | 658 | 667 | -9 |
| 2012-09-07 | vs TOR | 139 | L 5-7 | 61-78 | 4 | 37,156 | Felix Doubront | Henderson Alvarez | Henderson Alvarez | Felix Doubront | | 663 | 674 | -11 |
| 2012-09-08 | vs TOR | 140 | L 2-9 | 61-79 | 4 | 37,107 | Daisuke Matsuzaka | Aaron Laffey | Brad Lincoln | Daisuke Matsuzaka | | 665 | 683 | -18 |
| 2012-09-09 | vs TOR | 141 | L 3-4 | 61-80 | 5 | 37,226 | Clay Buchholz | Carlos Villanueva | Brandon Lyon | Clay Buchholz | Casey Janssen | 668 | 687 | -19 |
| 2012-09-11 | vs NYA | 142 | W 4-3 | 62-80 | 4 | 37,437 | Jon Lester | Hiroki Kuroda | Andrew Bailey | David Robertson | | 672 | 690 | -18 |
| 2012-09-12 | vs NYA | 143 | L 4-5 | 62-81 | 4 | 37,230 | Aaron Cook | David Phelps | David Phelps | Aaron Cook | Rafael Soriano | 676 | 695 | -19 |
| 2012-09-13 | vs NYA | 144 | L 0-2 | 62-82 | 5 | 38,134 | Felix Doubront | Phil Hughes | Phil Hughes | Felix Doubront | Rafael Soriano | 676 | 697 | -21 |
| 2012-09-14 | @ TOR | 145 | W 8-5 | 63-82 | 4 | 21,888 | Daisuke Matsuzaka | Aaron Laffey | Chris Carpenter | Darren Oliver | Andrew Bailey | 684 | 702 | -18 |
| 2012-09-15 | @ TOR | 146 | W 3-2 | 64-82 | 4 | 27,325 | Clay Buchholz | Carlos Villanueva | Craig Breslow | Steve Delabar | Andrew Bailey | 687 | 704 | -17 |
| 2012-09-16 | @ TOR | 147 | L 0-5 | 64-83 | 4 | 21,698 | Jon Lester | Brandon Morrow | Brandon Lyon | Jon Lester | | 687 | 709 | -22 |
| 2012-09-17 | @ TBA | 148 | W 5-2 | 65-83 | 4 | 11,722 | Aaron Cook | Alex Cobb | Aaron Cook | Alex Cobb | | 692 | 711 | -19 |
| 2012-09-18 | @ TBA | 149 | W 7-5 | 66-83 | 4 | 11,502 | Felix Doubront | Jeremy Hellickson | Felix Doubront | Kyle Farnsworth | Andrew Bailey | 699 | 716 | -17 |
| 2012-09-19 | @ TBA | 150 | W 3-13 | 67-83 | 5 | 12,708 | Daisuke Matsuzaka | Chris Archer | Chris Archer | Daisuke Matsuzaka | | 702 | 729 | -27 |
| 2012-09-20 | @ TBA | 151 | L 4-7 | 67-84 | 4 | 12,963 | Clay Buchholz | David Price | Burke Badenhop | Andrew Bailey | | 706 | 736 | -30 |
| 2012-09-21 | vs BAL | 152 | L 2-4 | 67-85 | 4 | 37,731 | Jon Lester | Miguel Gonzalez | Miguel Gonzalez | Jon Lester | Jim Johnson | 708 | 740 | -32 |
| 2012-09-22 | vs BAL | 153 | L 6-9 | 67-86 | 4 | 37,570 | Aaron Cook | Randy Wolf | Tommy Hunter | Alfredo Aceves | Jim Johnson | 714 | 749 | -35 |
| 2012-09-23 | vs BAL | 154 | W 2-1 | 68-86 | 4 | 37,310 | Felix Doubront | Chris Tillman | Junichi Tazawa | Luis Ayala | Andrew Bailey | 716 | 750 | -34 |
| 2012-09-25 | vs TBA | 155 | L 2-5 | 68-87 | 4 | 37,045 | Clay Buchholz | David Price | David Price | Clay Buchholz | | 718 | 755 | -37 |
| 2012-09-26 | vs TBA | 156 | L 2-4 | 68-88 | 5 | 37,247 | Jon Lester | Alex Cobb | Alex Cobb | Jon Lester | Fernando Rodney | 720 | 759 | -39 |
| 2012-09-28 | @ BAL | 157 | L 1-9 | 68-89 | 5 | 33,518 | Aaron Cook | Chris Tillman | Chris Tillman | Aaron Cook | | 721 | 768 | -47 |
| 2012-09-29 | @ BAL | 158 | L 3-4 | 68-90 | 5 | 46,311 | Felix Doubront | Steve Johnson | Tommy Hunter | Felix Doubront | Jim Johnson | 724 | 772 | -48 |
| 2012-09-30 | @ BAL | 159 | L 3-6 | 68-91 | 5 | 41,257 | Zach Stewart | Joe Saunders | Joe Saunders | Zach Stewart | Jim Johnson | 727 | 778 | -51 |
| 2012-10-01 | @ NYA | 160 | W 2-10 | 69-91 | 5 | 45,478 | Clay Buchholz | CC Sabathia | CC Sabathia | Clay Buchholz | | 729 | 788 | -59 |
| 2012-10-02 | @ NYA | 161 | L 3-4 | 69-92 | 5 | 41,564 | Jon Lester | David Phelps | Derek Lowe | Andrew Miller | | 732 | 792 | -60 |
| 2012-10-03 | @ NYA | 162 | W 2-14 | 70-92 | 5 | 47,393 | Daisuke Matsuzaka | Hiroki Kuroda | Hiroki Kuroda | Daisuke Matsuzaka | | 734 | 806 | -72 |