| 2010-04-06 | vs BAL | 1 | W 4-3 | 1-0 | 1 | 36,973 | James Shields | Kevin Millwood | Rafael Soriano | Mike Gonzalez | | 4 | 3 | 1 |
| 2010-04-07 | vs BAL | 2 | W 4-3 | 2-0 | 1 | 15,220 | Matt Garza | Jeremy Guthrie | Matt Garza | Jeremy Guthrie | Rafael Soriano | 8 | 6 | 2 |
| 2010-04-08 | vs BAL | 3 | L 4-5 | 2-1 | 1 | 16,191 | Jeff Niemann | Brian Matusz | Brian Matusz | Mike Ekstrom | Mike Gonzalez | 12 | 11 | 1 |
| 2010-04-09 | vs NYA | 4 | W 9-3 | 3-1 | 1 | 33,221 | David Price | Javier Vazquez | David Price | Javier Vazquez | | 21 | 14 | 7 |
| 2010-04-10 | vs NYA | 5 | L 0-10 | 3-2 | 3 | 29,892 | Wade Davis | CC Sabathia | CC Sabathia | Wade Davis | | 21 | 24 | -3 |
| 2010-04-11 | vs NYA | 6 | L 3-7 | 3-3 | 4 | 31,253 | James Shields | A.J. Burnett | A.J. Burnett | Randy Choate | | 24 | 31 | -7 |
| 2010-04-12 | @ BAL | 7 | W 5-1 | 4-3 | 3 | 9,129 | Matt Garza | Jeremy Guthrie | Matt Garza | Jeremy Guthrie | | 29 | 32 | -3 |
| 2010-04-13 | @ BAL | 8 | W 8-6 | 5-3 | 3 | 13,731 | Jeff Niemann | Brian Matusz | Lance Cormier | Matt Albers | Rafael Soriano | 37 | 38 | -1 |
| 2010-04-14 | @ BAL | 9 | W 9-1 | 6-3 | 1 | 10,248 | David Price | Brad Bergesen | David Price | Brad Bergesen | | 46 | 39 | 7 |
| 2010-04-16 | @ BOS | 10 | W 3-1 | 7-3 | 2 | 37,084 | Wade Davis | Josh Beckett | Lance Cormier | Manny Delcarmen | Rafael Soriano | 49 | 40 | 9 |
| 2010-04-17 | @ BOS | 11 | W 6-5 | 8-3 | 2 | 37,022 | James Shields | Clay Buchholz | James Shields | Clay Buchholz | Rafael Soriano | 55 | 45 | 10 |
| 2010-04-18 | @ BOS | 12 | W 7-1 | 9-3 | 2 | 37,143 | Matt Garza | Jon Lester | Matt Garza | Jon Lester | | 62 | 46 | 16 |
| 2010-04-19 | @ BOS | 13 | W 8-2 | 10-3 | 1 | 37,609 | Jeff Niemann | John Lackey | Jeff Niemann | John Lackey | | 70 | 48 | 22 |
| 2010-04-20 | @ CHA | 14 | L 1-4 | 10-4 | 2 | 19,260 | David Price | John Danks | John Danks | David Price | Bobby Jenks | 71 | 52 | 19 |
| 2010-04-21 | @ CHA | 15 | W 12-0 | 11-4 | 2 | 17,023 | Wade Davis | Mark Buehrle | Wade Davis | Mark Buehrle | | 83 | 52 | 31 |
| 2010-04-22 | @ CHA | 16 | W 10-2 | 11-5 | 2 | 18,207 | James Shields | Jake Peavy | James Shields | Jake Peavy | | 93 | 54 | 39 |
| 2010-04-23 | vs TOR | 17 | L 5-6 | 11-6 | 2 | 22,056 | Matt Garza | Brett Cecil | Brett Cecil | Matt Garza | Kevin Gregg | 98 | 60 | 38 |
| 2010-04-24 | vs TOR | 18 | W 9-3 | 12-6 | 2 | 23,870 | Jeff Niemann | Ricky Romero | Dan Wheeler | Scott Downs | | 107 | 63 | 44 |
| 2010-04-25 | vs TOR | 19 | W 6-0 | 13-6 | 1 | 23,250 | David Price | Brandon Morrow | David Price | Brandon Morrow | | 113 | 63 | 50 |
| 2010-04-27 | vs OAK | 20 | W 8-6 | 14-6 | 1 | 10,825 | Wade Davis | Ben Sheets | Wade Davis | Ben Sheets | Rafael Soriano | 121 | 69 | 52 |
| 2010-04-28 | vs OAK | 21 | W 10-3 | 14-7 | 1 | 10,691 | James Shields | Dallas Braden | James Shields | Dallas Braden | | 131 | 72 | 59 |
| 2010-04-29 | vs KCA | 22 | W 11-1 | 15-7 | 1 | 12,766 | Matt Garza | Luke Hochevar | Matt Garza | Luke Hochevar | | 142 | 73 | 69 |
| 2010-04-30 | vs KCA | 23 | L 2-3 | 15-8 | 2 | 25,195 | Jeff Niemann | Brian Bannister | Josh Rupe | Randy Choate | Joakim Soria | 144 | 76 | 68 |
| 2010-05-01 | vs KCA | 24 | L 2-4 | 15-9 | 2 | 34,813 | David Price | Kyle Davies | Rob Tejeda | Lance Cormier | Joakim Soria | 146 | 80 | 66 |
| 2010-05-02 | vs KCA | 25 | W 1-0 | 16-9 | 1 | 19,757 | Wade Davis | Zack Greinke | Wade Davis | Zack Greinke | Rafael Soriano | 147 | 80 | 67 |
| 2010-05-04 | @ SEA | 26 | W 5-2 | 17-9 | 2 | 15,589 | James Shields | Jason Vargas | James Shields | Jason Vargas | Rafael Soriano | 152 | 82 | 70 |
| 2010-05-05 | @ SEA | 27 | W 8-3 | 18-9 | 2 | 14,627 | Matt Garza | Cliff Lee | Matt Garza | Cliff Lee | | 160 | 85 | 75 |
| 2010-05-06 | @ SEA | 28 | W 8-0 | 19-9 | 1 | 17,617 | Jeff Niemann | Ryan Rowland-Smith | Jeff Niemann | Ryan Rowland-Smith | | 168 | 85 | 83 |
| 2010-05-07 | @ OAK | 29 | W 4-1 | 20-9 | 1 | 19,193 | David Price | Gio Gonzalez | David Price | Gio Gonzalez | Rafael Soriano | 172 | 86 | 86 |
| 2010-05-08 | @ OAK | 30 | L 2-4 | 20-10 | 1 | 15,493 | Wade Davis | Ben Sheets | Ben Sheets | Wade Davis | Andrew Bailey | 174 | 90 | 84 |
| 2010-05-09 | @ OAK | 31 | L 0-4 | 20-11 | 1 | 12,228 | James Shields | Dallas Braden | Dallas Braden | James Shields | | 174 | 94 | 80 |
| 2010-05-10 | @ ANA | 32 | L 4-5 | 20-12 | 1 | 36,798 | Matt Garza | Joel Pineiro | Trevor Bell | Grant Balfour | | 178 | 99 | 79 |
| 2010-05-11 | @ ANA | 33 | W 7-2 | 21-12 | 1 | 39,007 | Jeff Niemann | Scott Kazmir | Jeff Niemann | Scott Kazmir | | 185 | 101 | 84 |
| 2010-05-12 | @ ANA | 34 | W 4-3 | 22-12 | 1 | 35,700 | David Price | Jered Weaver | David Price | Jered Weaver | Rafael Soriano | 189 | 104 | 85 |
| 2010-05-14 | vs SEA | 35 | L 3-4 | 22-13 | 1 | 27,856 | Wade Davis | Doug Fister | Doug Fister | Wade Davis | David Aardsma | 192 | 108 | 84 |
| 2010-05-15 | vs SEA | 36 | W 3-2 | 23-13 | 1 | 23,627 | James Shields | Jason Vargas | Rafael Soriano | Jesus Colome | | 195 | 110 | 85 |
| 2010-05-16 | vs SEA | 37 | W 2-1 | 24-13 | 1 | 23,005 | Matt Garza | Cliff Lee | Dan Wheeler | Cliff Lee | Rafael Soriano | 197 | 111 | 86 |
| 2010-05-17 | vs CLE | 38 | W 4-3 | 25-13 | 1 | 18,879 | Jeff Niemann | Fausto Carmona | Andy Sonnanstine | Jamey Wright | | 201 | 114 | 87 |
| 2010-05-18 | vs CLE | 39 | W 6-2 | 26-13 | 1 | 17,093 | David Price | David Huff | David Price | David Huff | | 207 | 116 | 91 |
| 2010-05-19 | @ NYA | 40 | W 10-6 | 26-14 | 1 | 43,283 | Wade Davis | A.J. Burnett | Wade Davis | A.J. Burnett | Joaquin Benoit | 217 | 122 | 95 |
| 2010-05-20 | @ NYA | 41 | W 8-6 | 27-14 | 1 | 45,483 | James Shields | Andy Pettitte | James Shields | Andy Pettitte | Rafael Soriano | 225 | 128 | 97 |
| 2010-05-21 | @ HOU | 42 | L 1-2 | 27-15 | 1 | 27,601 | Matt Garza | Brett Myers | Brett Myers | Matt Garza | Matt Lindstrom | 226 | 130 | 96 |
| 2010-05-22 | @ HOU | 43 | W 4-2 | 28-15 | 1 | 33,778 | Jeff Niemann | Wandy Rodriguez | Jeff Niemann | Wandy Rodriguez | Rafael Soriano | 230 | 132 | 98 |
| 2010-05-23 | @ HOU | 44 | W 10-6 | 28-16 | 1 | 28,801 | David Price | Bud Norris | David Price | Brian Moehler | Rafael Soriano | 240 | 138 | 102 |
| 2010-05-24 | vs BOS | 45 | L 1-6 | 28-17 | 1 | 21,430 | Wade Davis | Clay Buchholz | Clay Buchholz | Wade Davis | | 241 | 144 | 97 |
| 2010-05-25 | vs BOS | 46 | L 0-2 | 28-18 | 1 | 24,310 | James Shields | Jon Lester | Jon Lester | James Shields | Jonathan Papelbon | 241 | 146 | 95 |
| 2010-05-26 | vs BOS | 47 | L 3-11 | 29-18 | 1 | 22,147 | Matt Garza | John Lackey | John Lackey | Matt Garza | | 244 | 157 | 87 |
| 2010-05-27 | vs CHA | 48 | W 5-1 | 30-18 | 1 | 13,299 | Jeff Niemann | Gavin Floyd | Jeff Niemann | Gavin Floyd | | 249 | 158 | 91 |
| 2010-05-28 | vs CHA | 49 | L 2-4 | 30-19 | 1 | 20,650 | David Price | Freddy Garcia | Freddy Garcia | David Price | Matt Thornton | 251 | 162 | 89 |
| 2010-05-29 | vs CHA | 50 | W 8-5 | 31-19 | 1 | 33,558 | Wade Davis | John Danks | Wade Davis | John Danks | Rafael Soriano | 259 | 167 | 92 |
| 2010-05-30 | vs CHA | 51 | L 5-8 | 31-20 | 1 | 26,878 | James Shields | Jake Peavy | Jake Peavy | James Shields | | 264 | 175 | 89 |
| 2010-05-31 | @ TOR | 52 | L 2-3 | 31-21 | 1 | 11,335 | Matt Garza | Brandon Morrow | Brandon Morrow | Matt Garza | Kevin Gregg | 266 | 178 | 88 |
| 2010-06-01 | @ TOR | 53 | W 7-6 | 32-21 | 2 | 13,439 | Jeff Niemann | Brian Tallet | Grant Balfour | Kevin Gregg | Rafael Soriano | 273 | 184 | 89 |
| 2010-06-02 | @ TOR | 54 | W 7-3 | 33-21 | 2 | 13,517 | David Price | Shaun Marcum | David Price | Shaun Marcum | | 280 | 187 | 93 |
| 2010-06-04 | @ TEX | 55 | L 6-9 | 33-22 | 2 | 36,245 | Wade Davis | C.J. Wilson | C.J. Wilson | Wade Davis | Neftali Feliz | 286 | 196 | 90 |
| 2010-06-05 | @ TEX | 56 | L 1-6 | 33-23 | 2 | 25,853 | James Shields | Tommy Hunter | Tommy Hunter | James Shields | | 287 | 202 | 85 |
| 2010-06-06 | @ TEX | 57 | W 9-5 | 34-23 | 2 | 26,932 | Matt Garza | Rich Harden | Matt Garza | Rich Harden | | 296 | 207 | 89 |
| 2010-06-08 | vs TOR | 58 | W 9-0 | 35-23 | 2 | 12,937 | Jeff Niemann | Brian Tallet | Jeff Niemann | Brian Tallet | | 305 | 207 | 98 |
| 2010-06-09 | vs TOR | 59 | W 10-1 | 36-23 | 1 | 15,886 | David Price | Shaun Marcum | David Price | Shaun Marcum | | 315 | 208 | 107 |
| 2010-06-10 | vs TOR | 60 | L 2-3 | 36-24 | 1 | 13,675 | Wade Davis | Brett Cecil | Brett Cecil | Wade Davis | Kevin Gregg | 317 | 211 | 106 |
| 2010-06-11 | vs FLO | 61 | L 9-14 | 37-24 | 1 | 19,338 | James Shields | Anibal Sanchez | Anibal Sanchez | James Shields | | 326 | 225 | 101 |
| 2010-06-12 | vs FLO | 62 | W 6-5 | 38-24 | 1 | 29,963 | Matt Garza | Ricky Nolasco | Matt Garza | Ricky Nolasco | Rafael Soriano | 332 | 230 | 102 |
| 2010-06-13 | vs FLO | 63 | L 1-6 | 38-25 | 1 | 25,442 | Jeff Niemann | Chris Volstad | Chris Volstad | Jeff Niemann | | 333 | 236 | 97 |
| 2010-06-15 | @ ATL | 64 | W 10-4 | 38-26 | 1 | 30,448 | David Price | Kenshin Kawakami | David Price | Kenshin Kawakami | | 343 | 240 | 103 |
| 2010-06-16 | @ ATL | 65 | L 2-6 | 38-27 | 1 | 26,807 | Wade Davis | Tommy Hanson | Tommy Hanson | Wade Davis | | 345 | 246 | 99 |
| 2010-06-17 | @ ATL | 66 | L 1-3 | 38-28 | 2 | 30,427 | James Shields | Tim Hudson | Tim Hudson | James Shields | Billy Wagner | 346 | 249 | 97 |
| 2010-06-18 | @ FLO | 67 | L 4-7 | 38-29 | 2 | 17,310 | Matt Garza | Nate Robertson | Nate Robertson | Matt Garza | Leo Nunez | 350 | 256 | 94 |
| 2010-06-19 | @ FLO | 68 | W 9-8 | 39-29 | 2 | 23,242 | Jeff Niemann | Chris Volstad | James Shields | Jorge Sosa | Andy Sonnanstine | 359 | 264 | 95 |
| 2010-06-20 | @ FLO | 69 | L 1-4 | 39-30 | 2 | 15,374 | David Price | Josh Johnson | Josh Johnson | David Price | Leo Nunez | 360 | 268 | 92 |
| 2010-06-22 | vs SDN | 70 | L 1-2 | 39-31 | 3 | 14,650 | Wade Davis | Mat Latos | Mat Latos | Wade Davis | Heath Bell | 361 | 270 | 91 |
| 2010-06-23 | vs SDN | 71 | L 4-5 | 39-32 | 3 | 15,809 | James Shields | Kevin Correia | Luke Gregerson | James Shields | Heath Bell | 365 | 275 | 90 |
| 2010-06-24 | vs SDN | 72 | W 5-3 | 40-32 | 3 | 21,877 | Matt Garza | Wade LeBlanc | Matt Garza | Wade LeBlanc | Rafael Soriano | 370 | 278 | 92 |
| 2010-06-25 | vs ARI | 73 | L 0-1 | 40-33 | 3 | 18,918 | Jeff Niemann | Edwin Jackson | Edwin Jackson | Jeff Niemann | | 370 | 279 | 91 |
| 2010-06-26 | vs ARI | 74 | W 5-3 | 41-33 | 3 | 23,945 | David Price | Ian Kennedy | David Price | Ian Kennedy | Rafael Soriano | 375 | 282 | 93 |
| 2010-06-27 | vs ARI | 75 | L 1-2 | 41-34 | 3 | 25,442 | Wade Davis | Rodrigo Lopez | Rodrigo Lopez | Wade Davis | Aaron Heilman | 376 | 284 | 92 |
| 2010-06-29 | @ BOS | 76 | L 5-8 | 41-35 | 3 | 38,013 | James Shields | John Lackey | John Lackey | James Shields | Jonathan Papelbon | 381 | 292 | 89 |
| 2010-06-30 | @ BOS | 77 | W 9-4 | 42-35 | 3 | 38,055 | Matt Garza | Daisuke Matsuzaka | Matt Garza | Daisuke Matsuzaka | | 390 | 296 | 94 |
| 2010-07-01 | @ MIN | 78 | W 5-4 | 43-35 | 3 | 40,665 | Jeff Niemann | Carl Pavano | Lance Cormier | Matt Guerrier | Rafael Soriano | 395 | 300 | 95 |
| 2010-07-02 | @ MIN | 79 | L 1-2 | 43-36 | 3 | 39,266 | David Price | Scott Baker | Scott Baker | David Price | Jon Rauch | 396 | 302 | 94 |
| 2010-07-03 | @ MIN | 80 | W 8-6 | 44-36 | 3 | 40,852 | Wade Davis | Francisco Liriano | Randy Choate | Matt Guerrier | Rafael Soriano | 404 | 308 | 96 |
| 2010-07-04 | @ MIN | 81 | W 7-4 | 45-36 | 3 | 40,328 | James Shields | Nick Blackburn | James Shields | Nick Blackburn | Rafael Soriano | 411 | 312 | 99 |
| 2010-07-05 | vs BOS | 82 | W 6-5 | 46-36 | 3 | 28,528 | Matt Garza | Daisuke Matsuzaka | Randy Choate | Ramon Ramirez | Rafael Soriano | 417 | 317 | 100 |
| 2010-07-06 | vs BOS | 83 | W 3-2 | 47-36 | 3 | 19,902 | Jeff Niemann | Felix Doubront | Jeff Niemann | Felix Doubront | Rafael Soriano | 420 | 319 | 101 |
| 2010-07-07 | vs BOS | 84 | W 6-4 | 48-36 | 2 | 24,356 | David Price | Tim Wakefield | David Price | Tim Wakefield | Matt Garza | 426 | 323 | 103 |
| 2010-07-08 | vs CLE | 85 | W 5-2 | 49-36 | 2 | 16,892 | Wade Davis | Jake Westbrook | Wade Davis | Jake Westbrook | Dan Wheeler | 431 | 325 | 106 |
| 2010-07-09 | vs CLE | 86 | L 3-9 | 49-37 | 2 | 23,116 | James Shields | Fausto Carmona | Fausto Carmona | James Shields | | 434 | 334 | 100 |
| 2010-07-10 | vs CLE | 87 | W 4-0 | 50-37 | 2 | 20,091 | Matt Garza | Aaron Laffey | Matt Garza | Aaron Laffey | | 438 | 334 | 104 |
| 2010-07-11 | vs CLE | 88 | W 6-5 | 51-37 | 2 | 24,687 | Jeff Niemann | Justin Masterson | Andy Sonnanstine | Kerry Wood | | 444 | 339 | 105 |
| 2010-07-16 | @ NYA | 89 | L 4-5 | 51-38 | 2 | 47,524 | James Shields | CC Sabathia | Mariano Rivera | Randy Choate | | 448 | 344 | 104 |
| 2010-07-17 | @ NYA | 90 | W 10-5 | 51-39 | 2 | 48,957 | Jeff Niemann | A.J. Burnett | Jeff Niemann | A.J. Burnett | | 458 | 349 | 109 |
| 2010-07-18 | @ NYA | 91 | L 5-9 | 51-40 | 2 | 46,969 | David Price | Andy Pettitte | Chan Ho Park | David Price | | 463 | 358 | 105 |
| 2010-07-19 | @ BAL | 92 | W 8-1 | 52-40 | 2 | 12,792 | Wade Davis | Chris Tillman | Wade Davis | Chris Tillman | | 471 | 359 | 112 |
| 2010-07-20 | @ BAL | 93 | L 10-11 | 52-41 | 2 | 16,623 | Matt Garza | Jake Arrieta | Koji Uehara | Lance Cormier | | 481 | 370 | 111 |
| 2010-07-21 | @ BAL | 94 | W 5-4 | 53-41 | 2 | 19,287 | James Shields | Brad Bergesen | James Shields | Brad Bergesen | Rafael Soriano | 486 | 374 | 112 |
| 2010-07-23 | @ CLE | 95 | L 1-3 | 53-42 | 2 | 16,904 | Jeff Niemann | Fausto Carmona | Fausto Carmona | Jeff Niemann | Tony Sipp | 487 | 377 | 110 |
| 2010-07-24 | @ CLE | 96 | W 6-3 | 54-42 | 2 | 17,221 | David Price | Mitch Talbot | David Price | Mitch Talbot | Rafael Soriano | 493 | 380 | 113 |
| 2010-07-25 | @ CLE | 97 | W 4-2 | 55-42 | 2 | 13,410 | Wade Davis | Justin Masterson | Wade Davis | Justin Masterson | Rafael Soriano | 497 | 382 | 115 |
| 2010-07-26 | vs DET | 98 | W 5-0 | 56-42 | 2 | 17,009 | Matt Garza | Max Scherzer | Matt Garza | Max Scherzer | | 502 | 382 | 120 |
| 2010-07-27 | vs DET | 99 | W 3-2 | 57-42 | 2 | 19,843 | James Shields | Justin Verlander | James Shields | Justin Verlander | Rafael Soriano | 505 | 384 | 121 |
| 2010-07-28 | vs DET | 100 | W 7-4 | 58-42 | 2 | 16,209 | Jeff Niemann | Eddie Bonine | Jeff Niemann | Eddie Bonine | Rafael Soriano | 512 | 388 | 124 |
| 2010-07-29 | vs DET | 101 | W 4-2 | 59-42 | 1 | 26,716 | David Price | Rick Porcello | David Price | Rick Porcello | Dan Wheeler | 516 | 390 | 126 |
| 2010-07-30 | vs NYA | 102 | W 3-2 | 60-42 | 1 | 36,973 | Wade Davis | Phil Hughes | Wade Davis | Phil Hughes | Rafael Soriano | 519 | 392 | 127 |
| 2010-07-31 | vs NYA | 103 | L 4-5 | 60-43 | 1 | 36,973 | Matt Garza | Javier Vazquez | David Robertson | Rafael Soriano | Mariano Rivera | 523 | 397 | 126 |
| 2010-08-01 | vs NYA | 104 | W 3-0 | 61-43 | 1 | 36,973 | James Shields | CC Sabathia | James Shields | CC Sabathia | Rafael Soriano | 526 | 397 | 129 |
| 2010-08-02 | vs MIN | 105 | W 4-2 | 62-43 | 1 | 17,689 | Jeremy Hellickson | Carl Pavano | Jeremy Hellickson | Carl Pavano | Dan Wheeler | 530 | 399 | 131 |
| 2010-08-03 | vs MIN | 106 | W 6-4 | 63-43 | 1 | 18,261 | Jeff Niemann | Brian Duensing | Jeff Niemann | Matt Guerrier | Rafael Soriano | 536 | 403 | 133 |
| 2010-08-04 | vs MIN | 107 | L 1-2 | 63-44 | 1 | 19,172 | David Price | Scott Baker | Matt Guerrier | Lance Cormier | | 537 | 405 | 132 |
| 2010-08-05 | vs MIN | 108 | L 6-8 | 63-45 | 1 | 29,210 | Wade Davis | Kevin Slowey | Matt Capps | Joaquin Benoit | | 543 | 413 | 130 |
| 2010-08-06 | @ TOR | 109 | L 1-2 | 63-46 | 1 | 22,520 | Matt Garza | Brett Cecil | Brett Cecil | Matt Garza | Kevin Gregg | 544 | 415 | 129 |
| 2010-08-07 | @ TOR | 110 | L 11-17 | 63-47 | 1 | 24,168 | James Shields | Brad Mills | Brian Tallet | James Shields | | 555 | 432 | 123 |
| 2010-08-08 | @ TOR | 111 | L 0-1 | 63-48 | 1 | 22,313 | Andy Sonnanstine | Brandon Morrow | Brandon Morrow | Andy Sonnanstine | | 555 | 433 | 122 |
| 2010-08-09 | @ DET | 112 | W 6-3 | 64-48 | 1 | 23,932 | David Price | Armando Galarraga | David Price | Armando Galarraga | Rafael Soriano | 561 | 436 | 125 |
| 2010-08-10 | @ DET | 113 | W 8-0 | 65-48 | 1 | 26,114 | Jeremy Hellickson | Max Scherzer | Jeremy Hellickson | Max Scherzer | | 569 | 436 | 133 |
| 2010-08-11 | @ DET | 114 | L 2-3 | 65-49 | 1 | 28,815 | Matt Garza | Justin Verlander | Justin Verlander | Matt Garza | Jose Valverde | 571 | 439 | 132 |
| 2010-08-13 | vs BAL | 115 | L 0-5 | 65-50 | 1 | 24,277 | James Shields | Jeremy Guthrie | Jeremy Guthrie | James Shields | | 571 | 444 | 127 |
| 2010-08-14 | vs BAL | 116 | W 7-3 | 66-50 | 1 | 36,189 | Andy Sonnanstine | Brian Matusz | Andy Sonnanstine | Brian Matusz | | 578 | 447 | 131 |
| 2010-08-15 | vs BAL | 117 | W 3-2 | 67-50 | 1 | 29,654 | Jeremy Hellickson | Jake Arrieta | Jeremy Hellickson | Jake Arrieta | Rafael Soriano | 581 | 449 | 132 |
| 2010-08-16 | vs TEX | 118 | W 6-4 | 68-50 | 1 | 18,319 | David Price | Cliff Lee | Lance Cormier | Cliff Lee | Rafael Soriano | 587 | 453 | 134 |
| 2010-08-17 | vs TEX | 119 | W 10-1 | 69-50 | 1 | 18,156 | Matt Garza | Tommy Hunter | Matt Garza | Tommy Hunter | | 597 | 454 | 143 |
| 2010-08-18 | vs TEX | 120 | W 8-6 | 70-50 | 1 | 19,413 | James Shields | Derek Holland | James Shields | Derek Holland | Rafael Soriano | 605 | 460 | 145 |
| 2010-08-19 | @ OAK | 121 | L 3-4 | 70-51 | 1 | 10,118 | Andy Sonnanstine | Trevor Cahill | Trevor Cahill | Dan Wheeler | Jerry Blevins | 608 | 464 | 144 |
| 2010-08-20 | @ OAK | 122 | L 4-5 | 70-52 | 1 | 13,207 | Jeremy Hellickson | Vin Mazzaro | Henry Rodriguez | Joaquin Benoit | Craig Breslow | 612 | 469 | 143 |
| 2010-08-21 | @ OAK | 123 | W 5-4 | 71-52 | 1 | 16,202 | David Price | Brett Anderson | Randy Choate | Craig Breslow | Rafael Soriano | 617 | 473 | 144 |
| 2010-08-22 | @ OAK | 124 | W 3-2 | 72-52 | 1 | 18,749 | Matt Garza | Dallas Braden | Matt Garza | Dallas Braden | Rafael Soriano | 620 | 475 | 145 |
| 2010-08-23 | @ ANA | 125 | W 4-3 | 73-52 | 1 | 39,127 | James Shields | Scott Kazmir | James Shields | Scott Kazmir | Rafael Soriano | 624 | 478 | 146 |
| 2010-08-24 | @ ANA | 126 | W 10-3 | 73-53 | 1 | 43,577 | Wade Davis | Ervin Santana | Wade Davis | Ervin Santana | | 634 | 481 | 153 |
| 2010-08-25 | @ ANA | 127 | L 3-12 | 74-53 | 1 | 37,009 | Jeff Niemann | Dan Haren | Dan Haren | Jeff Niemann | | 637 | 493 | 144 |
| 2010-08-27 | vs BOS | 128 | L 1-3 | 74-54 | 1 | 29,461 | David Price | Jon Lester | Jon Lester | David Price | Jonathan Papelbon | 638 | 496 | 142 |
| 2010-08-28 | vs BOS | 129 | W 3-2 | 75-54 | 1 | 36,973 | Matt Garza | Clay Buchholz | Randy Choate | Scott Atchison | | 641 | 498 | 143 |
| 2010-08-29 | vs BOS | 130 | W 5-3 | 76-54 | 1 | 23,438 | James Shields | John Lackey | James Shields | John Lackey | Rafael Soriano | 646 | 501 | 145 |
| 2010-08-30 | vs TOR | 131 | W 6-2 | 77-54 | 1 | 11,968 | Wade Davis | Brett Cecil | Wade Davis | Brett Cecil | | 652 | 503 | 149 |
| 2010-08-31 | vs TOR | 132 | L 5-13 | 78-54 | 1 | 12,972 | Jeff Niemann | Ricky Romero | Ricky Romero | Jeff Niemann | | 657 | 516 | 141 |
| 2010-09-01 | vs TOR | 133 | W 2-1 | 79-54 | 1 | 14,859 | David Price | Shaun Marcum | David Price | Shawn Camp | Rafael Soriano | 659 | 517 | 142 |
| 2010-09-03 | @ BAL | 134 | W 4-1 | 80-54 | 1 | 13,507 | Matt Garza | Kevin Millwood | Matt Garza | Kevin Millwood | Rafael Soriano | 663 | 518 | 145 |
| 2010-09-04 | @ BAL | 135 | L 4-8 | 80-55 | 1 | 18,943 | James Shields | Jeremy Guthrie | Jeremy Guthrie | James Shields | | 667 | 526 | 141 |
| 2010-09-05 | @ BAL | 136 | L 7-8 | 80-56 | 1 | 28,268 | Wade Davis | Chris Tillman | Alfredo Simon | Dan Wheeler | Koji Uehara | 674 | 534 | 140 |
| 2010-09-06 | @ BOS | 137 | L 5-12 | 81-56 | 1 | 37,546 | Jeff Niemann | Jon Lester | Jon Lester | Jeff Niemann | | 679 | 546 | 133 |
| 2010-09-07 | @ BOS | 138 | W 14-5 | 81-57 | 1 | 37,290 | David Price | Daisuke Matsuzaka | David Price | Daisuke Matsuzaka | | 693 | 551 | 142 |
| 2010-09-08 | @ BOS | 139 | L 5-11 | 82-57 | 1 | 37,757 | Matt Garza | Tim Wakefield | Tim Wakefield | Matt Garza | | 698 | 562 | 136 |
| 2010-09-10 | @ TOR | 140 | W 9-8 | 83-57 | 1 | 14,305 | James Shields | Brett Cecil | Joaquin Benoit | Kevin Gregg | Rafael Soriano | 707 | 570 | 137 |
| 2010-09-11 | @ TOR | 141 | W 13-1 | 84-57 | 1 | 17,632 | Wade Davis | Ricky Romero | Wade Davis | Ricky Romero | | 720 | 571 | 149 |
| 2010-09-12 | @ TOR | 142 | L 4-5 | 84-58 | 1 | 14,658 | Jeff Niemann | Shaun Marcum | Kevin Gregg | Rafael Soriano | | 724 | 576 | 148 |
| 2010-09-13 | vs NYA | 143 | W 1-0 | 85-58 | 1 | 26,907 | David Price | CC Sabathia | Grant Balfour | Sergio Mitre | | 725 | 576 | 149 |
| 2010-09-14 | vs NYA | 144 | L 7-8 | 85-59 | 1 | 28,713 | Matt Garza | Ivan Nova | David Robertson | Dan Wheeler | Mariano Rivera | 732 | 584 | 148 |
| 2010-09-15 | vs NYA | 145 | W 4-3 | 86-59 | 1 | 29,733 | James Shields | Phil Hughes | Chad Qualls | Phil Hughes | Rafael Soriano | 736 | 587 | 149 |
| 2010-09-17 | vs ANA | 146 | L 3-4 | 86-60 | 1 | 23,215 | Wade Davis | Dan Haren | Michael Kohn | Dan Wheeler | Fernando Rodney | 739 | 591 | 148 |
| 2010-09-18 | vs ANA | 147 | W 4-3 | 87-60 | 1 | 31,896 | David Price | Joel Pineiro | Rafael Soriano | Bobby Cassevah | | 743 | 594 | 149 |
| 2010-09-19 | vs ANA | 148 | L 3-6 | 87-61 | 1 | 25,794 | Jeff Niemann | Scott Kazmir | Scott Kazmir | Jeff Niemann | Jordan Walden | 746 | 600 | 146 |
| 2010-09-20 | @ NYA | 149 | L 6-8 | 87-62 | 1 | 47,437 | Matt Garza | Ivan Nova | Chad Gaudin | Matt Garza | Mariano Rivera | 752 | 608 | 144 |
| 2010-09-21 | @ NYA | 150 | L 3-8 | 87-63 | 1 | 46,609 | James Shields | Phil Hughes | Phil Hughes | James Shields | Joba Chamberlain | 755 | 616 | 139 |
| 2010-09-22 | @ NYA | 151 | W 7-2 | 88-63 | 1 | 46,986 | Wade Davis | A.J. Burnett | Jeremy Hellickson | A.J. Burnett | | 762 | 618 | 144 |
| 2010-09-23 | @ NYA | 152 | W 10-3 | 88-64 | 1 | 47,646 | David Price | CC Sabathia | David Price | CC Sabathia | | 772 | 621 | 151 |
| 2010-09-24 | vs SEA | 153 | W 5-3 | 89-64 | 1 | 17,840 | Jeff Niemann | Jason Vargas | Jeff Niemann | Jason Vargas | Rafael Soriano | 777 | 624 | 153 |
| 2010-09-25 | vs SEA | 154 | W 9-1 | 90-64 | 1 | 26,427 | Matt Garza | Doug Fister | Matt Garza | Doug Fister | | 786 | 625 | 161 |
| 2010-09-26 | vs SEA | 155 | L 2-6 | 90-65 | 1 | 22,301 | James Shields | Lucas French | Lucas French | James Shields | | 788 | 631 | 157 |
| 2010-09-27 | vs BAL | 156 | L 0-4 | 90-66 | 1 | 12,446 | Wade Davis | Brian Matusz | Brian Matusz | Wade Davis | | 788 | 635 | 153 |
| 2010-09-28 | vs BAL | 157 | W 5-0 | 91-66 | 1 | 17,891 | David Price | Brad Bergesen | David Price | Brad Bergesen | | 793 | 635 | 158 |
| 2010-09-29 | vs BAL | 158 | L 0-2 | 91-67 | 1 | 36,973 | Jeff Niemann | Kevin Millwood | Kevin Millwood | Jeff Niemann | Koji Uehara | 793 | 637 | 156 |
| 2010-09-30 | @ KCA | 159 | L 2-3 | 91-68 | 1 | 21,563 | Matt Garza | Zack Greinke | Zack Greinke | Matt Garza | Joakim Soria | 795 | 640 | 155 |
| 2010-10-01 | @ KCA | 160 | L 0-7 | 91-69 | 1 | 23,374 | James Shields | Bruce Chen | Bruce Chen | James Shields | | 795 | 647 | 148 |
| 2010-10-02 | @ KCA | 161 | W 4-0 | 92-69 | 1 | 32,484 | Andy Sonnanstine | Kyle Davies | Chad Qualls | Kyle Davies | | 799 | 647 | 152 |
| 2010-10-03 | @ KCA | 162 | W 3-2 | 93-69 | 1 | 20,936 | Wade Davis | Sean O'Sullivan | Jeff Niemann | Dusty Hughes | Rafael Soriano | 802 | 649 | 153 |