| 2011-04-01 | @ CLE | 1 | W 15-10 | 1-0 | 1 | 41,721 | Mark Buehrle | Fausto Carmona | Mark Buehrle | Fausto Carmona | | 15 | 10 | 5 |
| 2011-04-02 | @ CLE | 2 | W 8-3 | 2-0 | 1 | 9,853 | Edwin Jackson | Carlos Carrasco | Edwin Jackson | Carlos Carrasco | | 23 | 13 | 10 |
| 2011-04-03 | @ CLE | 3 | L 1-7 | 2-1 | 2 | 8,726 | John Danks | Justin Masterson | Justin Masterson | John Danks | | 24 | 20 | 4 |
| 2011-04-05 | @ KCA | 4 | L 6-7 | 2-2 | 2 | 12,641 | Gavin Floyd | Luke Hochevar | Jeremy Jeffress | Tony Pena | | 30 | 27 | 3 |
| 2011-04-06 | @ KCA | 5 | W 10-7 | 3-2 | 2 | 13,360 | Mark Buehrle | Jeff Francis | Chris Sale | Sean O'Sullivan | | 40 | 34 | 6 |
| 2011-04-07 | vs TBA | 6 | W 5-1 | 4-2 | 1 | 38,579 | Edwin Jackson | David Price | Edwin Jackson | David Price | | 45 | 35 | 10 |
| 2011-04-08 | vs TBA | 7 | L 7-9 | 4-3 | 2 | 20,199 | John Danks | James Shields | Adam Russell | Matt Thornton | Kyle Farnsworth | 52 | 44 | 8 |
| 2011-04-09 | vs TBA | 8 | W 4-2 | 5-3 | 2 | 26,378 | Philip Humber | Wade Davis | Philip Humber | Wade Davis | Chris Sale | 56 | 46 | 10 |
| 2011-04-10 | vs TBA | 9 | W 6-1 | 6-3 | 2 | 23,436 | Gavin Floyd | Jeff Niemann | Gavin Floyd | Jeff Niemann | | 62 | 47 | 15 |
| 2011-04-11 | vs OAK | 10 | L 1-2 | 6-4 | 3 | 20,057 | Mark Buehrle | Dallas Braden | Tyson Ross | Jesse Crain | Brian Fuentes | 63 | 49 | 14 |
| 2011-04-12 | vs OAK | 11 | W 6-5 | 7-4 | 2 | 18,020 | Edwin Jackson | Trevor Cahill | Chris Sale | Bobby Cramer | | 69 | 54 | 15 |
| 2011-04-13 | vs OAK | 12 | L 4-7 | 7-5 | 3 | 16,523 | John Danks | Brett Anderson | Grant Balfour | Matt Thornton | Brian Fuentes | 73 | 61 | 12 |
| 2011-04-15 | vs ANA | 13 | L 3-4 | 7-6 | 3 | 20,103 | Philip Humber | Jered Weaver | Jered Weaver | Philip Humber | Jordan Walden | 76 | 65 | 11 |
| 2011-04-16 | vs ANA | 14 | L 2-7 | 7-7 | 3 | 21,250 | Gavin Floyd | Tyler Chatwood | Tyler Chatwood | Gavin Floyd | | 78 | 72 | 6 |
| 2011-04-17 | vs ANA | 15 | L 2-4 | 7-8 | 3 | 23,458 | Mark Buehrle | Dan Haren | Dan Haren | Mark Buehrle | Jordan Walden | 80 | 76 | 4 |
| 2011-04-18 | @ TBA | 16 | L 0-5 | 7-9 | 4 | 12,016 | Edwin Jackson | David Price | David Price | Edwin Jackson | | 80 | 81 | -1 |
| 2011-04-19 | @ TBA | 17 | L 1-2 | 7-10 | 4 | 13,731 | John Danks | James Shields | James Shields | John Danks | | 81 | 83 | -2 |
| 2011-04-20 | @ TBA | 18 | L 1-4 | 7-11 | 4 | 13,214 | Philip Humber | Wade Davis | Wade Davis | Philip Humber | Kyle Farnsworth | 82 | 87 | -5 |
| 2011-04-21 | @ TBA | 19 | W 9-2 | 8-11 | 4 | 16,751 | Gavin Floyd | Jeff Niemann | Gavin Floyd | Jeff Niemann | | 91 | 89 | 2 |
| 2011-04-22 | @ DET | 20 | L 3-9 | 8-12 | 4 | 23,537 | Mark Buehrle | Justin Verlander | Justin Verlander | Mark Buehrle | | 94 | 98 | -4 |
| 2011-04-23 | @ DET | 21 | L 0-9 | 8-13 | 5 | 35,227 | Edwin Jackson | Brad Penny | Brad Penny | Edwin Jackson | | 94 | 107 | -13 |
| 2011-04-24 | @ DET | 22 | L 0-3 | 8-14 | 5 | 17,784 | John Danks | Max Scherzer | Max Scherzer | John Danks | Jose Valverde | 94 | 110 | -16 |
| 2011-04-25 | @ NYA | 23 | W 2-0 | 9-14 | 5 | 40,506 | Philip Humber | A.J. Burnett | Philip Humber | A.J. Burnett | Sergio Santos | 96 | 110 | -14 |
| 2011-04-26 | @ NYA | 24 | W 3-2 | 10-14 | 5 | 40,785 | Gavin Floyd | Ivan Nova | Gavin Floyd | Rafael Soriano | Sergio Santos | 99 | 112 | -13 |
| 2011-04-27 | @ NYA | 25 | L 1-3 | 10-15 | 5 | 40,586 | Mark Buehrle | Bartolo Colon | Bartolo Colon | Mark Buehrle | Mariano Rivera | 100 | 115 | -15 |
| 2011-04-28 | @ NYA | 26 | L 3-12 | 10-16 | 5 | 40,081 | Edwin Jackson | CC Sabathia | CC Sabathia | Edwin Jackson | | 103 | 127 | -24 |
| 2011-04-29 | vs BAL | 27 | L 4-10 | 10-17 | 4 | 21,816 | John Danks | Jake Arrieta | Jake Arrieta | John Danks | | 107 | 137 | -30 |
| 2011-04-30 | vs BAL | 28 | L 2-6 | 10-18 | 4 | 26,104 | Philip Humber | Chris Tillman | Chris Tillman | Philip Humber | | 109 | 143 | -34 |
| 2011-05-01 | vs BAL | 29 | L 4-6 | 10-19 | 4 | 22,029 | Gavin Floyd | Zachary Britton | Zachary Britton | Gavin Floyd | Kevin Gregg | 113 | 149 | -36 |
| 2011-05-02 | vs BAL | 30 | W 6-2 | 11-19 | 4 | 18,007 | Mark Buehrle | Jeremy Guthrie | Mark Buehrle | Jeremy Guthrie | Sergio Santos | 119 | 151 | -32 |
| 2011-05-03 | vs MIN | 31 | L 0-1 | 11-20 | 5 | 20,901 | Edwin Jackson | Francisco Liriano | Francisco Liriano | Edwin Jackson | | 119 | 152 | -33 |
| 2011-05-04 | vs MIN | 32 | L 2-3 | 11-21 | 5 | 18,028 | John Danks | Nick Blackburn | Nick Blackburn | John Danks | Matt Capps | 121 | 155 | -34 |
| 2011-05-06 | @ SEA | 33 | L 2-3 | 11-22 | 5 | 31,912 | Philip Humber | Felix Hernandez | Felix Hernandez | Matt Thornton | | 123 | 158 | -35 |
| 2011-05-07 | @ SEA | 34 | W 6-0 | 12-22 | 5 | 26,288 | Gavin Floyd | Doug Fister | Gavin Floyd | Doug Fister | | 129 | 158 | -29 |
| 2011-05-08 | @ SEA | 35 | W 5-2 | 13-22 | 5 | 26,074 | Mark Buehrle | Erik Bedard | Sergio Santos | Brandon League | | 134 | 160 | -26 |
| 2011-05-09 | @ ANA | 36 | W 8-0 | 14-22 | 4 | 38,561 | Edwin Jackson | Ervin Santana | Edwin Jackson | Ervin Santana | | 142 | 160 | -18 |
| 2011-05-10 | @ ANA | 37 | L 2-6 | 14-23 | 4 | 40,128 | John Danks | Joel Pineiro | Joel Pineiro | John Danks | | 144 | 166 | -22 |
| 2011-05-11 | @ ANA | 38 | W 6-4 | 15-23 | 4 | 39,151 | Jake Peavy | Tyler Chatwood | Sergio Santos | Kevin Jepsen | Matt Thornton | 150 | 170 | -20 |
| 2011-05-13 | @ OAK | 39 | W 4-3 | 16-23 | 4 | 12,690 | Philip Humber | Brandon McCarthy | Philip Humber | Brandon McCarthy | Sergio Santos | 154 | 173 | -19 |
| 2011-05-14 | @ OAK | 40 | L 2-6 | 16-24 | 4 | 17,291 | Gavin Floyd | Tyson Ross | Tyson Ross | Gavin Floyd | | 156 | 179 | -23 |
| 2011-05-15 | @ OAK | 41 | W 4-3 | 17-24 | 4 | 19,018 | Mark Buehrle | Trevor Cahill | Mark Buehrle | Trevor Cahill | Sergio Santos | 160 | 182 | -22 |
| 2011-05-16 | vs TEX | 42 | L 0-4 | 17-25 | 4 | 23,048 | Edwin Jackson | Colby Lewis | Colby Lewis | Edwin Jackson | | 160 | 186 | -26 |
| 2011-05-17 | vs TEX | 43 | W 4-3 | 18-25 | 4 | 22,437 | John Danks | Matt Harrison | Jesse Crain | Cody Eppley | Sergio Santos | 164 | 189 | -25 |
| 2011-05-18 | vs CLE | 44 | W 1-0 | 19-25 | 4 | 18,580 | Jake Peavy | Justin Masterson | Jake Peavy | Justin Masterson | | 165 | 189 | -24 |
| 2011-05-19 | vs CLE | 45 | W 8-2 | 20-25 | 4 | 22,077 | Gavin Floyd | Fausto Carmona | Gavin Floyd | Fausto Carmona | | 173 | 191 | -18 |
| 2011-05-20 | vs LAN | 46 | L 4-6 | 20-26 | 4 | 24,121 | Philip Humber | Ted Lilly | Kenley Jansen | Sergio Santos | Mike MacDougal | 177 | 197 | -20 |
| 2011-05-21 | vs LAN | 47 | W 9-2 | 21-26 | 4 | 25,519 | Mark Buehrle | Jon Garland | Mark Buehrle | Jon Garland | | 186 | 199 | -13 |
| 2011-05-22 | vs LAN | 48 | W 8-3 | 22-26 | 4 | 25,081 | Edwin Jackson | Hiroki Kuroda | Edwin Jackson | Hiroki Kuroda | Matt Thornton | 194 | 202 | -8 |
| 2011-05-23 | @ TEX | 49 | L 0-4 | 22-27 | 4 | 30,861 | John Danks | Alexi Ogando | Alexi Ogando | John Danks | | 194 | 206 | -12 |
| 2011-05-24 | @ TEX | 50 | W 8-6 | 23-27 | 4 | 35,524 | Jake Peavy | Derek Holland | Tony Pena | Brett Tomko | Sergio Santos | 202 | 212 | -10 |
| 2011-05-25 | @ TEX | 51 | L 1-2 | 23-28 | 4 | 32,382 | Gavin Floyd | C.J. Wilson | C.J. Wilson | Gavin Floyd | Neftali Feliz | 203 | 214 | -11 |
| 2011-05-26 | @ TOR | 52 | W 3-1 | 24-28 | 3 | 14,353 | Philip Humber | Brandon Morrow | Jesse Crain | Marc Rzepczynski | Sergio Santos | 206 | 215 | -9 |
| 2011-05-27 | @ TOR | 53 | L 2-4 | 24-29 | 4 | 16,668 | Mark Buehrle | Kyle Drabek | Casey Janssen | Mark Buehrle | Jon Rauch | 208 | 219 | -11 |
| 2011-05-28 | @ TOR | 54 | L 8-9 | 24-30 | 4 | 22,659 | Edwin Jackson | Carlos Villanueva | Luis Perez | Gavin Floyd | | 216 | 228 | -12 |
| 2011-05-29 | @ TOR | 55 | L 4-13 | 24-31 | 5 | 18,325 | John Danks | Ricky Romero | Ricky Romero | John Danks | | 220 | 241 | -21 |
| 2011-05-30 | @ BOS | 56 | W 7-3 | 25-31 | 3 | 37,463 | Jake Peavy | Jon Lester | Jake Peavy | Jon Lester | | 227 | 244 | -17 |
| 2011-05-31 | @ BOS | 57 | W 10-7 | 26-31 | 3 | 37,269 | Philip Humber | Alfredo Aceves | Philip Humber | Alfredo Aceves | Chris Sale | 237 | 251 | -14 |
| 2011-06-01 | @ BOS | 58 | W 7-4 | 27-31 | 3 | 37,321 | Gavin Floyd | Tim Wakefield | Gavin Floyd | Matt Albers | Sergio Santos | 244 | 255 | -11 |
| 2011-06-03 | vs DET | 59 | W 6-4 | 28-31 | 3 | 23,095 | Mark Buehrle | Andrew Oliver | Mark Buehrle | Andrew Oliver | Sergio Santos | 250 | 259 | -9 |
| 2011-06-04 | vs DET | 60 | L 2-4 | 28-32 | 3 | 31,037 | Edwin Jackson | Justin Verlander | Justin Verlander | Jesse Crain | Jose Valverde | 252 | 263 | -11 |
| 2011-06-05 | vs DET | 61 | L 3-7 | 28-33 | 3 | 25,149 | Jake Peavy | Brad Penny | Brad Penny | Jake Peavy | | 255 | 270 | -15 |
| 2011-06-06 | vs SEA | 62 | W 3-1 | 29-33 | 3 | 23,847 | John Danks | Michael Pineda | John Danks | Michael Pineda | Sergio Santos | 258 | 271 | -13 |
| 2011-06-07 | vs SEA | 63 | W 5-1 | 30-33 | 3 | 21,337 | Philip Humber | Felix Hernandez | Philip Humber | Felix Hernandez | | 263 | 272 | -9 |
| 2011-06-08 | vs SEA | 64 | L 4-7 | 30-34 | 3 | 21,517 | Gavin Floyd | Jason Vargas | Aaron Laffey | Sergio Santos | Brandon League | 267 | 279 | -12 |
| 2011-06-09 | vs OAK | 65 | W 9-4 | 31-34 | 3 | 22,170 | Mark Buehrle | Trevor Cahill | Mark Buehrle | Trevor Cahill | | 276 | 283 | -7 |
| 2011-06-10 | vs OAK | 66 | L 5-7 | 31-35 | 3 | 20,166 | Edwin Jackson | Graham Godfrey | Grant Balfour | Sergio Santos | Andrew Bailey | 281 | 290 | -9 |
| 2011-06-11 | vs OAK | 67 | W 3-2 | 32-35 | 3 | 24,391 | John Danks | Gio Gonzalez | John Danks | Gio Gonzalez | Jesse Crain | 284 | 292 | -8 |
| 2011-06-12 | vs OAK | 68 | W 5-4 | 33-35 | 3 | 22,144 | Philip Humber | Guillermo Moscoso | Philip Humber | Guillermo Moscoso | Sergio Santos | 289 | 296 | -7 |
| 2011-06-15 | @ MIN | 69 | L 1-4 | 33-36 | 3 | 37,437 | Gavin Floyd | Carl Pavano | Carl Pavano | Gavin Floyd | | 290 | 300 | -10 |
| 2011-06-16 | @ MIN | 70 | L 0-1 | 33-37 | 3 | 39,484 | Mark Buehrle | Nick Blackburn | Nick Blackburn | Mark Buehrle | Matt Capps | 290 | 301 | -11 |
| 2011-06-17 | @ ARI | 71 | L 1-4 | 33-38 | 3 | 26,053 | Edwin Jackson | Daniel Hudson | Daniel Hudson | Edwin Jackson | | 291 | 305 | -14 |
| 2011-06-18 | @ ARI | 72 | W 6-2 | 34-38 | 3 | 33,230 | John Danks | Zach Duke | John Danks | Zach Duke | | 297 | 307 | -10 |
| 2011-06-19 | @ ARI | 73 | W 8-2 | 35-38 | 3 | 39,538 | Philip Humber | Josh Collmenter | Philip Humber | Josh Collmenter | | 305 | 309 | -4 |
| 2011-06-20 | vs CHN | 74 | L 3-6 | 35-39 | 3 | 36,005 | Gavin Floyd | Carlos Zambrano | Carlos Zambrano | Gavin Floyd | Carlos Marmol | 308 | 315 | -7 |
| 2011-06-21 | vs CHN | 75 | W 3-2 | 36-39 | 3 | 35,155 | Mark Buehrle | Matt Garza | Jesse Crain | Jeff Samardzija | Sergio Santos | 311 | 317 | -6 |
| 2011-06-22 | vs CHN | 76 | W 4-3 | 37-39 | 3 | 35,403 | Jake Peavy | Doug Davis | Jake Peavy | Doug Davis | Sergio Santos | 315 | 320 | -5 |
| 2011-06-24 | vs WAS | 77 | L 5-9 | 37-40 | 3 | 23,856 | Edwin Jackson | Jordan Zimmermann | Collin Balester | Matt Thornton | | 320 | 329 | -9 |
| 2011-06-25 | vs WAS | 78 | W 3-0 | 38-40 | 3 | 23,008 | John Danks | Tom Gorzelanny | Jake Peavy | Tom Gorzelanny | Sergio Santos | 323 | 329 | -6 |
| 2011-06-26 | vs WAS | 79 | L 1-2 | 38-41 | 3 | 24,057 | Philip Humber | Livan Hernandez | Livan Hernandez | Philip Humber | Drew Storen | 324 | 331 | -7 |
| 2011-06-28 | @ COL | 80 | L 2-3 | 38-42 | 3 | 40,175 | Gavin Floyd | Jason Hammel | Rex Brothers | Will Ohman | | 326 | 334 | -8 |
| 2011-06-29 | @ COL | 81 | W 3-2 | 39-42 | 3 | 35,973 | Mark Buehrle | Ubaldo Jimenez | Brian Bruney | Huston Street | Sergio Santos | 329 | 336 | -7 |
| 2011-06-30 | @ COL | 82 | W 6-4 | 40-42 | 3 | 38,084 | Jake Peavy | Aaron Cook | Jesse Crain | Clayton Mortensen | Sergio Santos | 335 | 340 | -5 |
| 2011-07-01 | @ CHN | 83 | W 6-4 | 41-42 | 3 | 41,486 | Edwin Jackson | Randy Wells | Edwin Jackson | Randy Wells | Sergio Santos | 341 | 344 | -3 |
| 2011-07-02 | @ CHN | 84 | W 1-0 | 42-42 | 3 | 42,165 | Philip Humber | Matt Garza | Philip Humber | Matt Garza | Matt Thornton | 342 | 344 | -2 |
| 2011-07-03 | @ CHN | 85 | L 1-3 | 42-43 | 3 | 42,311 | Gavin Floyd | Rodrigo Lopez | Rodrigo Lopez | Gavin Floyd | Carlos Marmol | 343 | 347 | -4 |
| 2011-07-04 | vs KCA | 86 | W 5-4 | 43-43 | 3 | 31,077 | Mark Buehrle | Jeff Francis | Sergio Santos | Aaron Crow | | 348 | 351 | -3 |
| 2011-07-05 | vs KCA | 87 | L 3-5 | 43-44 | 3 | 20,695 | Jake Peavy | Felipe Paulino | Felipe Paulino | Jake Peavy | Joakim Soria | 351 | 356 | -5 |
| 2011-07-06 | vs KCA | 88 | L 1-4 | 43-45 | 3 | 27,233 | Edwin Jackson | Bruce Chen | Bruce Chen | Edwin Jackson | Joakim Soria | 352 | 360 | -8 |
| 2011-07-07 | vs MIN | 89 | L 2-6 | 43-46 | 3 | 26,395 | Philip Humber | Carl Pavano | Carl Pavano | Philip Humber | | 354 | 366 | -12 |
| 2011-07-08 | vs MIN | 90 | L 5-8 | 43-47 | 3 | 27,737 | Gavin Floyd | Nick Blackburn | Nick Blackburn | Gavin Floyd | Matt Capps | 359 | 374 | -15 |
| 2011-07-09 | vs MIN | 91 | W 4-3 | 44-47 | 3 | 30,055 | Mark Buehrle | Brian Duensing | Jesse Crain | Jose Mijares | | 363 | 377 | -14 |
| 2011-07-10 | vs MIN | 92 | L 3-6 | 44-48 | 3 | 30,042 | Jake Peavy | Anthony Swarzak | Anthony Swarzak | Jake Peavy | Matt Capps | 366 | 383 | -17 |
| 2011-07-15 | @ DET | 93 | W 8-2 | 45-48 | 3 | 43,593 | Gavin Floyd | Justin Verlander | Gavin Floyd | Justin Verlander | | 374 | 385 | -11 |
| 2011-07-16 | @ DET | 94 | W 5-0 | 46-48 | 3 | 40,984 | Edwin Jackson | Max Scherzer | Edwin Jackson | Max Scherzer | | 379 | 385 | -6 |
| 2011-07-17 | @ DET | 95 | L 3-4 | 46-49 | 3 | 37,049 | Philip Humber | Brad Penny | Brad Penny | Philip Humber | Jose Valverde | 382 | 389 | -7 |
| 2011-07-18 | @ KCA | 96 | W 5-2 | 47-49 | 4 | 17,190 | Mark Buehrle | Kyle Davies | Mark Buehrle | Kyle Davies | | 387 | 391 | -4 |
| 2011-07-19 | @ KCA | 97 | L 2-4 | 47-50 | 3 | 20,126 | Jake Peavy | Danny Duffy | Danny Duffy | Jake Peavy | Joakim Soria | 389 | 395 | -6 |
| 2011-07-20 | @ KCA | 98 | L 1-2 | 47-51 | 3 | 13,831 | John Danks | Bruce Chen | Aaron Crow | Chris Sale | | 390 | 397 | -7 |
| 2011-07-22 | @ CLE | 99 | W 3-0 | 48-51 | 3 | 27,477 | Gavin Floyd | Carlos Carrasco | Gavin Floyd | Carlos Carrasco | Sergio Santos | 393 | 397 | -4 |
| 2011-07-24 | @ CLE | 100 | W 4-2 | 49-51 | 3 | 20,252 | Edwin Jackson | Justin Masterson | Edwin Jackson | Justin Masterson | Sergio Santos | 397 | 399 | -2 |
| 2011-07-25 | vs DET | 101 | W 6-3 | 50-51 | 3 | 37,110 | Mark Buehrle | Duane Below | Mark Buehrle | Duane Below | | 403 | 402 | 1 |
| 2011-07-26 | vs DET | 102 | L 4-5 | 50-52 | 3 | 28,093 | Jake Peavy | Justin Verlander | Justin Verlander | Will Ohman | Jose Valverde | 407 | 407 | 0 |
| 2011-07-27 | vs DET | 103 | W 2-1 | 51-52 | 3 | 26,978 | John Danks | Max Scherzer | John Danks | Max Scherzer | Sergio Santos | 409 | 408 | 1 |
| 2011-07-29 | vs BOS | 104 | W 3-1 | 52-52 | 3 | 27,513 | Gavin Floyd | Tim Wakefield | Gavin Floyd | Tim Wakefield | Sergio Santos | 412 | 409 | 3 |
| 2011-07-30 | vs BOS | 105 | L 2-10 | 52-53 | 3 | 33,919 | Philip Humber | Jon Lester | Jon Lester | Philip Humber | | 414 | 419 | -5 |
| 2011-07-31 | vs BOS | 106 | L 3-5 | 52-54 | 3 | 28,278 | Mark Buehrle | Andrew Miller | Alfredo Aceves | Jesse Crain | Jonathan Papelbon | 417 | 424 | -7 |
| 2011-08-01 | vs NYA | 107 | L 2-3 | 52-55 | 3 | 24,142 | Jake Peavy | CC Sabathia | CC Sabathia | Jake Peavy | Mariano Rivera | 419 | 427 | -8 |
| 2011-08-02 | vs NYA | 108 | L 0-6 | 52-56 | 3 | 21,661 | John Danks | Phil Hughes | Phil Hughes | John Danks | | 419 | 433 | -14 |
| 2011-08-03 | vs NYA | 109 | L 7-18 | 52-57 | 3 | 23,873 | Gavin Floyd | A.J. Burnett | Cory Wade | Gavin Floyd | | 426 | 451 | -25 |
| 2011-08-04 | vs NYA | 110 | L 2-7 | 52-58 | 3 | 28,088 | Philip Humber | Ivan Nova | Ivan Nova | Philip Humber | | 428 | 458 | -30 |
| 2011-08-05 | @ MIN | 111 | W 5-3 | 53-58 | 3 | 41,364 | Mark Buehrle | Nick Blackburn | Mark Buehrle | Nick Blackburn | Chris Sale | 433 | 461 | -28 |
| 2011-08-06 | @ MIN | 112 | W 6-1 | 54-58 | 3 | 41,030 | Zach Stewart | Carl Pavano | Zach Stewart | Carl Pavano | | 439 | 462 | -23 |
| 2011-08-07 | @ MIN | 113 | W 7-0 | 55-58 | 3 | 39,353 | Jake Peavy | Brian Duensing | Jake Peavy | Brian Duensing | | 446 | 462 | -16 |
| 2011-08-08 | @ BAL | 114 | W 7-6 | 56-58 | 3 | 17,498 | John Danks | Jeremy Guthrie | Jesse Crain | Jim Johnson | Sergio Santos | 453 | 468 | -15 |
| 2011-08-09 | @ BAL | 115 | W 4-3 | 57-58 | 3 | 14,177 | Gavin Floyd | Jo-Jo Reyes | Gavin Floyd | Jo-Jo Reyes | Sergio Santos | 457 | 471 | -14 |
| 2011-08-10 | @ BAL | 116 | L 4-6 | 57-59 | 3 | 18,747 | Philip Humber | Tommy Hunter | Mike Gonzalez | Jason Frasor | | 461 | 477 | -16 |
| 2011-08-11 | @ BAL | 117 | W 6-3 | 58-59 | 3 | 21,040 | Mark Buehrle | Chris Tillman | Mark Buehrle | Chris Tillman | Sergio Santos | 467 | 480 | -13 |
| 2011-08-12 | vs KCA | 118 | L 1-5 | 58-60 | 3 | 23,130 | Zach Stewart | Bruce Chen | Bruce Chen | Zach Stewart | Greg Holland | 468 | 485 | -17 |
| 2011-08-13 | vs KCA | 119 | W 5-4 | 59-60 | 3 | 24,854 | Jake Peavy | Luke Hochevar | Jesse Crain | Luke Hochevar | Chris Sale | 473 | 489 | -16 |
| 2011-08-14 | vs KCA | 120 | W 6-2 | 60-60 | 3 | 25,517 | John Danks | Jeff Francis | John Danks | Jeff Francis | | 479 | 491 | -12 |
| 2011-08-16 | vs CLE | 121 | W 8-7 | 61-60 | 3 | 24,695 | Gavin Floyd | Ubaldo Jimenez | Jason Frasor | Chad Durbin | | 487 | 498 | -11 |
| 2011-08-17 | vs CLE | 122 | L 1-4 | 61-61 | 3 | 25,029 | Mark Buehrle | Fausto Carmona | Fausto Carmona | Mark Buehrle | Chris Perez | 488 | 502 | -14 |
| 2011-08-18 | vs CLE | 123 | L 2-4 | 61-62 | 3 | 27,079 | Philip Humber | Justin Masterson | Justin Masterson | Will Ohman | Chris Perez | 490 | 506 | -16 |
| 2011-08-19 | vs TEX | 124 | L 4-7 | 61-63 | 3 | 28,308 | Jake Peavy | Matt Harrison | Yoshinori Tateyama | Jake Peavy | Neftali Feliz | 494 | 513 | -19 |
| 2011-08-20 | vs TEX | 125 | W 3-2 | 62-63 | 3 | 30,021 | John Danks | Alexi Ogando | Jesse Crain | Koji Uehara | Sergio Santos | 497 | 515 | -18 |
| 2011-08-21 | vs TEX | 126 | W 10-0 | 63-63 | 3 | 25,033 | Gavin Floyd | Derek Holland | Gavin Floyd | Derek Holland | | 507 | 515 | -8 |
| 2011-08-23 | @ ANA | 127 | L 4-5 | 63-64 | 4 | 37,728 | Mark Buehrle | Ervin Santana | Jordan Walden | Jason Frasor | | 511 | 520 | -9 |
| 2011-08-24 | @ ANA | 128 | L 0-8 | 63-65 | 3 | 36,610 | Zach Stewart | Jered Weaver | Jered Weaver | Zach Stewart | | 511 | 528 | -17 |
| 2011-08-26 | @ SEA | 129 | W 4-2 | 64-65 | 3 | 28,621 | Jake Peavy | Charlie Furbush | Jake Peavy | Charlie Furbush | Chris Sale | 515 | 530 | -15 |
| 2011-08-27 | @ SEA | 130 | W 3-0 | 65-65 | 3 | 30,522 | John Danks | Michael Pineda | John Danks | Michael Pineda | | 518 | 530 | -12 |
| 2011-08-28 | @ SEA | 131 | W 9-3 | 66-65 | 2 | 25,630 | Gavin Floyd | Jason Vargas | Gavin Floyd | Jason Vargas | | 527 | 533 | -6 |
| 2011-08-29 | vs MIN | 132 | W 3-0 | 67-65 | 2 | 24,120 | Mark Buehrle | Kevin Slowey | Mark Buehrle | Kevin Slowey | Sergio Santos | 530 | 533 | -3 |
| 2011-08-30 | vs MIN | 133 | W 8-6 | 68-65 | 2 | 21,632 | Zach Stewart | Anthony Swarzak | Will Ohman | Anthony Swarzak | Sergio Santos | 538 | 539 | -1 |
| 2011-08-31 | vs MIN | 134 | L 6-7 | 68-66 | 3 | 20,346 | Jake Peavy | Scott Diamond | Scott Diamond | Jake Peavy | Joe Nathan | 544 | 546 | -2 |
| 2011-09-02 | @ DET | 135 | L 1-8 | 68-67 | 3 | 42,352 | John Danks | Justin Verlander | Justin Verlander | John Danks | | 545 | 554 | -9 |
| 2011-09-03 | @ DET | 136 | L 8-9 | 68-68 | 3 | 40,635 | Gavin Floyd | Brad Penny | Luis Marte | Sergio Santos | | 553 | 563 | -10 |
| 2011-09-04 | @ DET | 137 | L 2-18 | 68-69 | 3 | 42,671 | Mark Buehrle | Max Scherzer | Max Scherzer | Mark Buehrle | | 555 | 581 | -26 |
| 2011-09-05 | @ MIN | 138 | W 2-1 | 69-69 | 4 | 40,252 | Philip Humber | Anthony Swarzak | Philip Humber | Anthony Swarzak | Chris Sale | 557 | 582 | -25 |
| 2011-09-05 | @ MIN | 139 | W 4-0 | 69-69 | 4 | 39,849 | Zach Stewart | Scott Diamond | Zach Stewart | Scott Diamond | | 561 | 582 | -21 |
| 2011-09-06 | @ MIN | 140 | W 3-0 | 71-69 | 2 | 36,959 | Jake Peavy | Liam Hendriks | Jake Peavy | Liam Hendriks | Sergio Santos | 564 | 582 | -18 |
| 2011-09-07 | @ MIN | 141 | L 4-5 | 71-70 | 2 | 38,359 | John Danks | Carl Pavano | Carl Pavano | John Danks | Joe Nathan | 568 | 587 | -19 |
| 2011-09-08 | vs CLE | 142 | W 8-1 | 72-70 | 2 | 22,063 | Gavin Floyd | David Huff | Matt Thornton | David Huff | | 576 | 588 | -12 |
| 2011-09-09 | vs CLE | 143 | L 4-8 | 72-71 | 2 | 26,711 | Mark Buehrle | Jeanmar Gomez | Jeanmar Gomez | Mark Buehrle | | 580 | 596 | -16 |
| 2011-09-10 | vs CLE | 144 | W 7-3 | 73-71 | 2 | 26,719 | Philip Humber | Fausto Carmona | Sergio Santos | Chris Perez | | 587 | 599 | -12 |
| 2011-09-11 | vs CLE | 145 | L 3-7 | 73-72 | 2 | 22,319 | Zach Stewart | Ubaldo Jimenez | Ubaldo Jimenez | Zach Stewart | | 590 | 606 | -16 |
| 2011-09-12 | vs DET | 146 | L 4-14 | 73-73 | 2 | 22,750 | John Danks | Rick Porcello | Rick Porcello | John Danks | | 594 | 620 | -26 |
| 2011-09-13 | vs DET | 147 | L 0-5 | 73-74 | 2 | 25,015 | Gavin Floyd | Justin Verlander | Justin Verlander | Gavin Floyd | | 594 | 625 | -31 |
| 2011-09-14 | vs DET | 148 | L 5-6 | 73-75 | 2 | 19,010 | Dylan Axelrod | Brad Penny | Phil Coke | Sergio Santos | Jose Valverde | 599 | 631 | -32 |
| 2011-09-15 | @ KCA | 149 | L 2-7 | 73-76 | 2 | 17,737 | Mark Buehrle | Jeff Francis | Jeff Francis | Mark Buehrle | | 601 | 638 | -37 |
| 2011-09-16 | @ KCA | 150 | L 6-7 | 73-77 | 3 | 24,918 | Philip Humber | Felipe Paulino | Greg Holland | Matt Thornton | | 607 | 645 | -38 |
| 2011-09-17 | @ KCA | 151 | L 3-10 | 73-78 | 3 | 31,264 | Zach Stewart | Everett Teaford | Everett Teaford | Zach Stewart | Nathan Adcock | 610 | 655 | -45 |
| 2011-09-18 | @ KCA | 152 | W 10-5 | 74-78 | 3 | 29,480 | John Danks | Bruce Chen | John Danks | Bruce Chen | | 620 | 660 | -40 |
| 2011-09-20 | @ CLE | 153 | L 3-4 | 74-79 | 5 | 28,603 | Gavin Floyd | Fausto Carmona | Fausto Carmona | Gavin Floyd | Chris Perez | 623 | 664 | -41 |
| 2011-09-20 | @ CLE | 154 | W 5-4 | 74-79 | 5 | 19,582 | Dylan Axelrod | Zach McAllister | Matt Thornton | Zach Putnam | Chris Sale | 628 | 668 | -40 |
| 2011-09-21 | @ CLE | 155 | W 8-4 | 76-79 | 3 | 12,400 | Mark Buehrle | Ubaldo Jimenez | Mark Buehrle | Ubaldo Jimenez | | 636 | 672 | -36 |
| 2011-09-22 | @ CLE | 156 | L 2-11 | 76-80 | 3 | 21,487 | Philip Humber | Jeanmar Gomez | Jeanmar Gomez | Philip Humber | | 638 | 683 | -45 |
| 2011-09-23 | vs KCA | 157 | L 1-11 | 76-81 | 3 | 21,744 | Zach Stewart | Bruce Chen | Bruce Chen | Zach Stewart | | 639 | 694 | -55 |
| 2011-09-24 | vs KCA | 158 | W 6-3 | 77-81 | 4 | 26,249 | John Danks | Everett Teaford | John Danks | Everett Teaford | | 645 | 697 | -52 |
| 2011-09-25 | vs KCA | 159 | L 1-2 | 77-82 | 3 | 22,018 | Gavin Floyd | Luis Mendoza | Luis Mendoza | Gavin Floyd | Greg Holland | 646 | 699 | -53 |
| 2011-09-26 | vs TOR | 160 | W 4-3 | 78-82 | 3 | 21,320 | Dylan Axelrod | Dustin McGowan | Dylan Axelrod | Dustin McGowan | Sergio Santos | 650 | 702 | -52 |
| 2011-09-27 | vs TOR | 161 | W 2-1 | 79-82 | 3 | 23,934 | Mark Buehrle | Henderson Alvarez | Mark Buehrle | Henderson Alvarez | Chris Sale | 652 | 703 | -51 |
| 2011-09-28 | vs TOR | 162 | L 2-3 | 79-83 | 3 | 20,524 | Philip Humber | Brandon Morrow | Shawn Camp | Chris Sale | Frank Francisco | 654 | 706 | -52 |