| 2010-04-06 | @ TBA | 1 | L 3-4 | 0-1 | 4 | 36,973 | Kevin Millwood | James Shields | Rafael Soriano | Mike Gonzalez | | 3 | 4 | -1 |
| 2010-04-07 | @ TBA | 2 | L 3-4 | 0-2 | 5 | 15,220 | Jeremy Guthrie | Matt Garza | Matt Garza | Jeremy Guthrie | Rafael Soriano | 6 | 8 | -2 |
| 2010-04-08 | @ TBA | 3 | W 5-4 | 1-2 | 4 | 16,191 | Brian Matusz | Jeff Niemann | Brian Matusz | Mike Ekstrom | Mike Gonzalez | 11 | 12 | -1 |
| 2010-04-09 | vs TOR | 4 | L 6-7 | 1-3 | 4 | 48,891 | Brad Bergesen | Brandon Morrow | Casey Janssen | Mike Gonzalez | Kevin Gregg | 17 | 19 | -2 |
| 2010-04-10 | vs TOR | 5 | L 0-3 | 1-4 | 5 | 21,148 | David Hernandez | Dana Eveland | Dana Eveland | David Hernandez | Jason Frasor | 17 | 22 | -5 |
| 2010-04-11 | vs TOR | 6 | L 2-5 | 1-5 | 5 | 22,499 | Kevin Millwood | Shaun Marcum | Casey Janssen | Kevin Millwood | Kevin Gregg | 19 | 27 | -8 |
| 2010-04-12 | vs TBA | 7 | L 1-5 | 1-6 | 5 | 9,129 | Jeremy Guthrie | Matt Garza | Matt Garza | Jeremy Guthrie | | 20 | 32 | -12 |
| 2010-04-13 | vs TBA | 8 | L 6-8 | 1-7 | 5 | 13,731 | Brian Matusz | Jeff Niemann | Lance Cormier | Matt Albers | Rafael Soriano | 26 | 40 | -14 |
| 2010-04-14 | vs TBA | 9 | L 1-9 | 1-8 | 5 | 10,248 | Brad Bergesen | David Price | David Price | Brad Bergesen | | 27 | 49 | -22 |
| 2010-04-15 | @ OAK | 10 | L 2-6 | 1-9 | 5 | 17,382 | David Hernandez | Ben Sheets | Ben Sheets | David Hernandez | | 29 | 55 | -26 |
| 2010-04-16 | @ OAK | 11 | L 2-4 | 1-10 | 5 | 12,225 | Kevin Millwood | Dallas Braden | Dallas Braden | Kevin Millwood | Andrew Bailey | 31 | 59 | -28 |
| 2010-04-17 | @ OAK | 12 | L 3-4 | 1-11 | 5 | 15,072 | Jeremy Guthrie | Justin Duchscherer | Jerry Blevins | Jim Johnson | | 34 | 63 | -29 |
| 2010-04-18 | @ OAK | 13 | W 8-3 | 2-11 | 5 | 14,451 | Brian Matusz | Brett Anderson | Brian Matusz | Brett Anderson | Jim Johnson | 42 | 66 | -24 |
| 2010-04-19 | @ SEA | 14 | L 2-8 | 2-12 | 5 | 14,528 | Brad Bergesen | Doug Fister | Doug Fister | Brad Bergesen | | 44 | 74 | -30 |
| 2010-04-20 | @ SEA | 15 | L 1-3 | 2-13 | 5 | 15,931 | David Hernandez | Jason Vargas | Jason Vargas | David Hernandez | David Aardsma | 45 | 77 | -32 |
| 2010-04-21 | @ SEA | 16 | L 1-4 | 2-14 | 5 | 18,401 | Kevin Millwood | Felix Hernandez | Felix Hernandez | Kevin Millwood | | 46 | 81 | -35 |
| 2010-04-23 | @ BOS | 17 | L 3-4 | 2-15 | 5 | 37,367 | Jeremy Guthrie | Jon Lester | Manny Delcarmen | Matt Albers | Jonathan Papelbon | 49 | 85 | -36 |
| 2010-04-24 | @ BOS | 18 | L 6-7 | 2-16 | 5 | 38,017 | Brian Matusz | John Lackey | John Lackey | Matt Albers | Jonathan Papelbon | 55 | 92 | -37 |
| 2010-04-25 | @ BOS | 19 | W 7-6 | 3-16 | 5 | 37,102 | David Hernandez | Tim Wakefield | Jim Johnson | Scott Atchison | Cla Meredith | 62 | 98 | -36 |
| 2010-04-27 | vs NYA | 20 | W 5-4 | 4-16 | 5 | 20,536 | Kevin Millwood | Phil Hughes | Alberto Castillo | David Robertson | Alfredo Simon | 67 | 102 | -35 |
| 2010-04-28 | vs NYA | 21 | L 3-8 | 4-17 | 5 | 17,248 | Jeremy Guthrie | CC Sabathia | CC Sabathia | Jeremy Guthrie | | 70 | 110 | -40 |
| 2010-04-29 | vs NYA | 22 | L 0-4 | 4-18 | 5 | 26,439 | Brian Matusz | A.J. Burnett | A.J. Burnett | Brian Matusz | | 70 | 114 | -44 |
| 2010-04-30 | vs BOS | 23 | W 5-4 | 5-18 | 5 | 30,668 | David Hernandez | John Lackey | Matt Albers | Ramon Ramirez | | 75 | 118 | -43 |
| 2010-05-01 | vs BOS | 24 | W 12-9 | 5-19 | 5 | 35,164 | Brad Bergesen | Daisuke Matsuzaka | Brad Bergesen | Daisuke Matsuzaka | Alfredo Simon | 87 | 127 | -40 |
| 2010-05-02 | vs BOS | 25 | W 3-2 | 6-19 | 5 | 34,255 | Kevin Millwood | Josh Beckett | Matt Albers | Jonathan Papelbon | | 90 | 129 | -39 |
| 2010-05-03 | @ NYA | 26 | L 1-4 | 6-20 | 5 | 41,571 | Jeremy Guthrie | CC Sabathia | CC Sabathia | Jeremy Guthrie | Joba Chamberlain | 91 | 133 | -42 |
| 2010-05-04 | @ NYA | 27 | L 1-4 | 6-21 | 5 | 43,260 | Brian Matusz | A.J. Burnett | A.J. Burnett | Brian Matusz | Joba Chamberlain | 92 | 137 | -45 |
| 2010-05-05 | @ NYA | 28 | L 5-7 | 6-22 | 5 | 43,425 | David Hernandez | Andy Pettitte | Andy Pettitte | David Hernandez | Alfredo Aceves | 97 | 144 | -47 |
| 2010-05-06 | @ MIN | 29 | W 2-0 | 7-22 | 5 | 38,489 | Brad Bergesen | Carl Pavano | Brad Bergesen | Carl Pavano | Alfredo Simon | 99 | 144 | -45 |
| 2010-05-08 | @ MIN | 30 | W 7-3 | 8-23 | 6 | 38,608 | Jeremy Guthrie | Francisco Liriano | Jeremy Guthrie | Francisco Liriano | | 106 | 147 | -41 |
| 2010-05-08 | @ MIN | 31 | L 1-6 | 8-23 | 6 | 38,863 | Kevin Millwood | Scott Baker | Scott Baker | Kevin Millwood | | 107 | 153 | -46 |
| 2010-05-09 | @ MIN | 32 | L 0-6 | 8-24 | 5 | 38,641 | Brian Matusz | Nick Blackburn | Nick Blackburn | Brian Matusz | | 107 | 159 | -52 |
| 2010-05-11 | vs SEA | 33 | L 1-5 | 8-25 | 5 | 12,614 | David Hernandez | Cliff Lee | Cliff Lee | David Hernandez | Brandon League | 108 | 164 | -56 |
| 2010-05-12 | vs SEA | 34 | W 5-2 | 9-25 | 6 | 11,448 | Brad Bergesen | Ryan Rowland-Smith | Brad Bergesen | Ryan Rowland-Smith | Alfredo Simon | 113 | 166 | -53 |
| 2010-05-13 | vs SEA | 35 | W 6-5 | 10-25 | 5 | 20,938 | Kevin Millwood | Felix Hernandez | Mark Hendrickson | Brandon League | Alfredo Simon | 119 | 171 | -52 |
| 2010-05-14 | vs CLE | 36 | W 8-1 | 11-25 | 5 | 25,902 | Jeremy Guthrie | Justin Masterson | Jeremy Guthrie | Justin Masterson | | 127 | 172 | -45 |
| 2010-05-15 | vs CLE | 37 | L 2-8 | 11-26 | 5 | 29,545 | Brian Matusz | Mitch Talbot | Mitch Talbot | Alfredo Simon | | 129 | 180 | -51 |
| 2010-05-16 | vs CLE | 38 | L 1-5 | 11-27 | 5 | 29,323 | Mark Hendrickson | Jake Westbrook | Jake Westbrook | Mark Hendrickson | | 130 | 185 | -55 |
| 2010-05-17 | vs KCA | 39 | L 3-4 | 11-28 | 5 | 9,299 | Brad Bergesen | Kyle Davies | Kyle Davies | Brad Bergesen | Joakim Soria | 133 | 189 | -56 |
| 2010-05-18 | vs KCA | 40 | W 4-3 | 12-28 | 5 | 9,715 | Kevin Millwood | Zack Greinke | Alfredo Simon | Bryan Bullington | | 137 | 192 | -55 |
| 2010-05-19 | @ TEX | 41 | L 3-4 | 12-29 | 5 | 22,321 | Jeremy Guthrie | Rich Harden | Frank Francisco | Cla Meredith | | 140 | 196 | -56 |
| 2010-05-20 | @ TEX | 42 | L 7-13 | 13-29 | 5 | 17,304 | Brian Matusz | Scott Feldman | Scott Feldman | Brian Matusz | | 147 | 209 | -62 |
| 2010-05-21 | @ WAS | 43 | W 5-3 | 14-29 | 5 | 27,378 | David Hernandez | Scott Olsen | David Hernandez | Scott Olsen | Alfredo Simon | 152 | 212 | -60 |
| 2010-05-22 | @ WAS | 44 | L 6-7 | 14-30 | 5 | 30,290 | Brad Bergesen | Craig Stammen | Tyler Walker | Mark Hendrickson | Matt Capps | 158 | 219 | -61 |
| 2010-05-23 | @ WAS | 45 | L 3-4 | 14-31 | 5 | 27,535 | Kevin Millwood | John Lannan | Doug Slaten | Cla Meredith | | 161 | 223 | -62 |
| 2010-05-25 | vs OAK | 46 | W 5-1 | 15-31 | 5 | 14,686 | Jeremy Guthrie | Dallas Braden | Jeremy Guthrie | Tyson Ross | | 166 | 224 | -58 |
| 2010-05-26 | vs OAK | 47 | L 1-6 | 15-32 | 5 | 19,153 | Brian Matusz | Trevor Cahill | Trevor Cahill | Brian Matusz | | 167 | 230 | -63 |
| 2010-05-27 | vs OAK | 48 | L 5-7 | 15-33 | 5 | 26,279 | Brad Bergesen | Gio Gonzalez | Michael Wuertz | Mark Hendrickson | Andrew Bailey | 172 | 237 | -65 |
| 2010-05-28 | @ TOR | 49 | L 0-5 | 15-34 | 5 | 16,360 | Kevin Millwood | Shaun Marcum | Shaun Marcum | Kevin Millwood | | 172 | 242 | -70 |
| 2010-05-29 | @ TOR | 50 | L 2-5 | 15-35 | 5 | 16,194 | Chris Tillman | Brett Cecil | Brett Cecil | Jason Berken | Kevin Gregg | 174 | 247 | -73 |
| 2010-05-30 | @ TOR | 51 | L 1-6 | 15-36 | 5 | 15,878 | Jeremy Guthrie | Ricky Romero | Ricky Romero | Jeremy Guthrie | | 175 | 253 | -78 |
| 2010-06-01 | @ NYA | 52 | L 1-3 | 15-37 | 5 | 43,059 | Brian Matusz | Javier Vazquez | Javier Vazquez | Brian Matusz | Mariano Rivera | 176 | 256 | -80 |
| 2010-06-02 | @ NYA | 53 | L 1-9 | 15-38 | 5 | 44,465 | Brad Bergesen | Phil Hughes | Phil Hughes | Brad Bergesen | | 177 | 265 | -88 |
| 2010-06-03 | @ NYA | 54 | L 3-6 | 15-39 | 5 | 44,927 | Kevin Millwood | CC Sabathia | CC Sabathia | Kevin Millwood | Mariano Rivera | 180 | 271 | -91 |
| 2010-06-04 | vs BOS | 55 | L 0-11 | 15-40 | 5 | 30,070 | Chris Tillman | Clay Buchholz | Clay Buchholz | Chris Tillman | | 180 | 282 | -102 |
| 2010-06-05 | vs BOS | 56 | L 2-8 | 15-41 | 5 | 40,001 | Jeremy Guthrie | Jon Lester | Jon Lester | Jeremy Guthrie | | 182 | 290 | -108 |
| 2010-06-06 | vs BOS | 57 | W 4-3 | 16-41 | 5 | 27,774 | Brian Matusz | John Lackey | David Hernandez | Hideki Okajima | | 186 | 293 | -107 |
| 2010-06-08 | vs NYA | 58 | L 7-12 | 17-41 | 5 | 23,171 | Kevin Millwood | Phil Hughes | Phil Hughes | Kevin Millwood | | 193 | 305 | -112 |
| 2010-06-09 | vs NYA | 59 | L 2-4 | 17-42 | 5 | 16,451 | Chris Tillman | CC Sabathia | CC Sabathia | Chris Tillman | Mariano Rivera | 195 | 309 | -114 |
| 2010-06-10 | vs NYA | 60 | W 4-3 | 18-42 | 5 | 27,064 | Jake Arrieta | A.J. Burnett | Jake Arrieta | A.J. Burnett | David Hernandez | 199 | 312 | -113 |
| 2010-06-11 | vs NYN | 61 | L 1-5 | 18-43 | 5 | 28,554 | Jeremy Guthrie | R.A. Dickey | R.A. Dickey | Jeremy Guthrie | | 200 | 317 | -117 |
| 2010-06-12 | vs NYN | 62 | L 1-3 | 18-44 | 5 | 42,248 | Brian Matusz | Hisanori Takahashi | Hisanori Takahashi | Brian Matusz | Francisco Rodriguez | 201 | 320 | -119 |
| 2010-06-13 | vs NYN | 63 | L 4-11 | 19-44 | 5 | 24,848 | Kevin Millwood | Mike Pelfrey | Mike Pelfrey | Kevin Millwood | | 205 | 331 | -126 |
| 2010-06-14 | @ SFN | 64 | L 2-10 | 20-44 | 5 | 33,822 | Chris Tillman | Jonathan Sanchez | Jonathan Sanchez | Chris Tillman | | 207 | 341 | -134 |
| 2010-06-15 | @ SFN | 65 | W 4-1 | 21-44 | 5 | 35,498 | Jake Arrieta | Joe Martinez | Jake Arrieta | Joe Martinez | David Hernandez | 211 | 342 | -131 |
| 2010-06-16 | @ SFN | 66 | L 3-6 | 21-45 | 5 | 38,485 | Jeremy Guthrie | Tim Lincecum | Tim Lincecum | Jeremy Guthrie | Brian Wilson | 214 | 348 | -134 |
| 2010-06-18 | @ SDN | 67 | L 2-3 | 21-46 | 5 | 25,167 | Brian Matusz | Wade LeBlanc | Heath Bell | David Hernandez | | 216 | 351 | -135 |
| 2010-06-19 | @ SDN | 68 | W 5-4 | 22-46 | 5 | 28,138 | Kevin Millwood | Clayton Richard | Kevin Millwood | Clayton Richard | Alfredo Simon | 221 | 355 | -134 |
| 2010-06-20 | @ SDN | 69 | L 4-9 | 22-47 | 5 | 28,029 | Jake Arrieta | Jon Garland | Jon Garland | Jake Arrieta | | 225 | 364 | -139 |
| 2010-06-22 | vs FLO | 70 | L 4-10 | 23-47 | 5 | 14,821 | Jeremy Guthrie | Anibal Sanchez | Anibal Sanchez | Jeremy Guthrie | | 229 | 374 | -145 |
| 2010-06-23 | vs FLO | 71 | L 5-7 | 23-48 | 5 | 13,720 | Brian Matusz | Ricky Nolasco | Ricky Nolasco | Brian Matusz | Leo Nunez | 234 | 381 | -147 |
| 2010-06-24 | vs FLO | 72 | W 11-5 | 23-49 | 5 | 15,397 | Kevin Millwood | Nate Robertson | Kevin Millwood | Nate Robertson | | 245 | 386 | -141 |
| 2010-06-25 | vs WAS | 73 | W 7-6 | 24-49 | 5 | 43,484 | Jake Arrieta | J.D. Martin | Alfredo Simon | Tyler Clippard | | 252 | 392 | -140 |
| 2010-06-26 | vs WAS | 74 | W 6-5 | 25-49 | 5 | 28,635 | Brad Bergesen | Livan Hernandez | Jason Berken | Sean Burnett | Alfredo Simon | 258 | 397 | -139 |
| 2010-06-27 | vs WAS | 75 | W 4-3 | 26-49 | 5 | 22,951 | Jeremy Guthrie | Luis Atilano | David Hernandez | Tyler Clippard | Alfredo Simon | 262 | 400 | -138 |
| 2010-06-29 | vs OAK | 76 | L 2-4 | 26-50 | 5 | 11,987 | Brian Matusz | Vin Mazzaro | Vin Mazzaro | Brian Matusz | Andrew Bailey | 264 | 404 | -140 |
| 2010-06-30 | vs OAK | 77 | W 9-6 | 27-50 | 5 | 21,392 | Kevin Millwood | Ben Sheets | Matt Albers | Cedrick Bowers | Alfredo Simon | 273 | 410 | -137 |
| 2010-07-01 | vs OAK | 78 | L 1-8 | 27-51 | 5 | 15,712 | Jake Arrieta | Trevor Cahill | Trevor Cahill | Jake Arrieta | | 274 | 418 | -144 |
| 2010-07-02 | @ BOS | 79 | L 2-3 | 27-52 | 5 | 38,067 | Brad Bergesen | Tim Wakefield | Tim Wakefield | Brad Bergesen | Jonathan Papelbon | 276 | 421 | -145 |
| 2010-07-03 | @ BOS | 80 | L 3-9 | 27-53 | 5 | 38,106 | Jeremy Guthrie | Jon Lester | Jon Lester | Jeremy Guthrie | | 279 | 430 | -151 |
| 2010-07-04 | @ BOS | 81 | W 6-1 | 28-53 | 5 | 37,742 | Brian Matusz | John Lackey | Brian Matusz | John Lackey | | 285 | 431 | -146 |
| 2010-07-05 | @ DET | 82 | L 9-12 | 29-53 | 5 | 26,432 | Kevin Millwood | Andrew Oliver | Eddie Bonine | Mark Hendrickson | | 294 | 443 | -149 |
| 2010-07-06 | @ DET | 83 | L 5-7 | 29-54 | 5 | 22,532 | Jake Arrieta | Armando Galarraga | Ryan Perry | David Hernandez | | 299 | 450 | -151 |
| 2010-07-07 | @ DET | 84 | L 2-4 | 29-55 | 5 | 22,837 | Brad Bergesen | Max Scherzer | Max Scherzer | Brad Bergesen | Phil Coke | 301 | 454 | -153 |
| 2010-07-08 | @ TEX | 85 | W 6-4 | 30-55 | 5 | 16,240 | Jeremy Guthrie | Tommy Hunter | David Hernandez | Frank Francisco | Alfredo Simon | 307 | 458 | -151 |
| 2010-07-09 | @ TEX | 86 | W 7-6 | 31-55 | 5 | 24,216 | Brian Matusz | Scott Feldman | Jason Berken | Dustin Nippert | Alfredo Simon | 314 | 464 | -150 |
| 2010-07-10 | @ TEX | 87 | W 6-1 | 32-55 | 5 | 41,093 | Chris Tillman | Cliff Lee | Chris Tillman | Cliff Lee | | 320 | 465 | -145 |
| 2010-07-11 | @ TEX | 88 | W 4-1 | 33-55 | 5 | 24,566 | Jake Arrieta | C.J. Wilson | Jake Arrieta | C.J. Wilson | Alfredo Simon | 324 | 466 | -142 |
| 2010-07-16 | vs TOR | 89 | L 2-4 | 33-56 | 5 | 18,120 | Brad Bergesen | Ricky Romero | Ricky Romero | Brad Bergesen | Kevin Gregg | 326 | 470 | -144 |
| 2010-07-17 | vs TOR | 90 | L 2-3 | 33-57 | 5 | 28,518 | Jeremy Guthrie | Brandon Morrow | Brandon Morrow | Jason Berken | Shawn Camp | 328 | 473 | -145 |
| 2010-07-18 | vs TOR | 91 | L 1-10 | 33-58 | 5 | 14,032 | Brian Matusz | Shaun Marcum | Shaun Marcum | Brian Matusz | | 329 | 483 | -154 |
| 2010-07-19 | vs TBA | 92 | L 1-8 | 33-59 | 5 | 12,792 | Chris Tillman | Wade Davis | Wade Davis | Chris Tillman | | 330 | 491 | -161 |
| 2010-07-20 | vs TBA | 93 | W 11-10 | 34-59 | 5 | 16,623 | Jake Arrieta | Matt Garza | Koji Uehara | Lance Cormier | | 341 | 501 | -160 |
| 2010-07-21 | vs TBA | 94 | L 4-5 | 34-60 | 5 | 19,287 | Brad Bergesen | James Shields | James Shields | Brad Bergesen | Rafael Soriano | 345 | 506 | -161 |
| 2010-07-22 | vs MIN | 95 | L 0-5 | 34-61 | 5 | 20,108 | Kevin Millwood | Carl Pavano | Carl Pavano | Kevin Millwood | | 345 | 511 | -166 |
| 2010-07-23 | vs MIN | 96 | W 3-2 | 35-61 | 5 | 19,013 | Jeremy Guthrie | Brian Duensing | Jeremy Guthrie | Anthony Slama | Alfredo Simon | 348 | 513 | -165 |
| 2010-07-24 | vs MIN | 97 | L 2-7 | 35-62 | 5 | 22,299 | Brian Matusz | Scott Baker | Scott Baker | Brian Matusz | | 350 | 520 | -170 |
| 2010-07-25 | vs MIN | 98 | L 4-10 | 36-62 | 6 | 17,408 | Jake Arrieta | Kevin Slowey | Kevin Slowey | Jake Arrieta | | 354 | 530 | -176 |
| 2010-07-26 | @ TOR | 99 | L 5-9 | 36-63 | 5 | 17,422 | Brad Bergesen | Brandon Morrow | Brandon Morrow | Brad Bergesen | David Purcey | 359 | 539 | -180 |
| 2010-07-27 | @ TOR | 100 | L 2-8 | 36-64 | 5 | 16,862 | Kevin Millwood | Ricky Romero | Ricky Romero | Kevin Millwood | | 361 | 547 | -186 |
| 2010-07-28 | @ TOR | 101 | L 0-5 | 36-65 | 5 | 17,041 | Jeremy Guthrie | Brad Mills | Brad Mills | Jeremy Guthrie | | 361 | 552 | -191 |
| 2010-07-29 | @ KCA | 102 | W 6-5 | 37-65 | 5 | 17,220 | Brian Matusz | Kyle Davies | David Hernandez | Blake Wood | Alfredo Simon | 367 | 557 | -190 |
| 2010-07-30 | @ KCA | 103 | L 5-7 | 37-66 | 5 | 21,537 | Jake Arrieta | Sean O'Sullivan | Blake Wood | Alfredo Simon | | 372 | 564 | -192 |
| 2010-07-31 | @ KCA | 104 | L 3-4 | 37-67 | 5 | 25,055 | Brad Bergesen | Zack Greinke | Zack Greinke | David Hernandez | Joakim Soria | 375 | 568 | -193 |
| 2010-08-01 | @ KCA | 105 | L 4-5 | 37-68 | 5 | 14,662 | Kevin Millwood | Bruce Chen | Bruce Chen | Kevin Millwood | Joakim Soria | 379 | 573 | -194 |
| 2010-08-03 | vs ANA | 106 | W 6-3 | 38-68 | 5 | 16,723 | Jeremy Guthrie | Trevor Bell | Jeremy Guthrie | Francisco Rodriguez | | 385 | 576 | -191 |
| 2010-08-04 | vs ANA | 107 | W 9-7 | 39-68 | 5 | 13,467 | Brian Matusz | Ervin Santana | Brian Matusz | Ervin Santana | Alfredo Simon | 394 | 583 | -189 |
| 2010-08-05 | vs ANA | 108 | W 5-4 | 40-68 | 5 | 17,362 | Jake Arrieta | Dan Haren | Jason Berken | Francisco Rodriguez | | 399 | 587 | -188 |
| 2010-08-06 | vs CHA | 109 | W 2-1 | 41-68 | 5 | 19,687 | Brad Bergesen | John Danks | Alfredo Simon | Tony Pena | | 401 | 588 | -187 |
| 2010-08-07 | vs CHA | 110 | L 2-4 | 41-69 | 5 | 24,929 | Kevin Millwood | Gavin Floyd | Gavin Floyd | Jason Berken | J.J. Putz | 403 | 592 | -189 |
| 2010-08-08 | vs CHA | 111 | W 4-3 | 42-69 | 5 | 18,283 | Jeremy Guthrie | Mark Buehrle | Jeremy Guthrie | Mark Buehrle | Alfredo Simon | 407 | 595 | -188 |
| 2010-08-09 | vs CHA | 112 | W 3-2 | 43-69 | 5 | 14,135 | Brian Matusz | Edwin Jackson | Matt Albers | J.J. Putz | | 410 | 597 | -187 |
| 2010-08-10 | @ CLE | 113 | W 14-8 | 43-70 | 5 | 13,541 | Jake Arrieta | Justin Masterson | Jake Arrieta | Justin Masterson | | 424 | 605 | -181 |
| 2010-08-11 | @ CLE | 114 | W 3-1 | 44-70 | 5 | 11,155 | Brad Bergesen | Josh Tomlin | Brad Bergesen | Josh Tomlin | | 427 | 606 | -179 |
| 2010-08-12 | @ CLE | 115 | L 1-4 | 44-71 | 5 | 14,533 | Kevin Millwood | Jeanmar Gomez | Jeanmar Gomez | Kevin Millwood | Chris Perez | 428 | 610 | -182 |
| 2010-08-13 | @ TBA | 116 | W 5-0 | 45-71 | 5 | 24,277 | Jeremy Guthrie | James Shields | Jeremy Guthrie | James Shields | | 433 | 610 | -177 |
| 2010-08-14 | @ TBA | 117 | L 3-7 | 45-72 | 5 | 36,189 | Brian Matusz | Andy Sonnanstine | Andy Sonnanstine | Brian Matusz | | 436 | 617 | -181 |
| 2010-08-15 | @ TBA | 118 | L 2-3 | 45-73 | 5 | 29,654 | Jake Arrieta | Jeremy Hellickson | Jeremy Hellickson | Jake Arrieta | Rafael Soriano | 438 | 620 | -182 |
| 2010-08-16 | vs SEA | 119 | W 5-4 | 46-73 | 5 | 12,375 | Brad Bergesen | Doug Fister | Matt Albers | Sean White | | 443 | 624 | -181 |
| 2010-08-17 | vs SEA | 120 | L 0-4 | 46-74 | 5 | 14,739 | Kevin Millwood | Lucas French | Lucas French | Kevin Millwood | Brandon League | 443 | 628 | -185 |
| 2010-08-18 | vs SEA | 121 | L 5-6 | 46-75 | 5 | 11,213 | Jeremy Guthrie | David Pauley | David Pauley | Jeremy Guthrie | David Aardsma | 448 | 634 | -186 |
| 2010-08-19 | vs TEX | 122 | W 4-0 | 47-75 | 5 | 14,635 | Brian Matusz | Colby Lewis | Brian Matusz | Colby Lewis | | 452 | 634 | -182 |
| 2010-08-20 | vs TEX | 123 | L 0-2 | 47-76 | 5 | 18,751 | Jake Arrieta | C.J. Wilson | C.J. Wilson | Jake Arrieta | Neftali Feliz | 452 | 636 | -184 |
| 2010-08-21 | vs TEX | 124 | W 8-6 | 48-76 | 5 | 23,041 | Brad Bergesen | Cliff Lee | Brad Bergesen | Cliff Lee | Koji Uehara | 460 | 642 | -182 |
| 2010-08-22 | vs TEX | 125 | L 4-6 | 48-77 | 5 | 14,788 | Kevin Millwood | Tommy Hunter | Tommy Hunter | Kevin Millwood | Neftali Feliz | 464 | 648 | -184 |
| 2010-08-24 | @ CHA | 126 | L 5-7 | 48-78 | 5 | 26,263 | Jeremy Guthrie | Gavin Floyd | Gavin Floyd | Jeremy Guthrie | Bobby Jenks | 469 | 655 | -186 |
| 2010-08-25 | @ CHA | 127 | W 4-2 | 49-78 | 6 | 23,733 | Brian Matusz | Mark Buehrle | Brian Matusz | Mark Buehrle | Koji Uehara | 473 | 657 | -184 |
| 2010-08-26 | @ CHA | 128 | L 0-8 | 49-79 | 5 | 23,898 | Jake Arrieta | Edwin Jackson | Edwin Jackson | Jake Arrieta | | 473 | 665 | -192 |
| 2010-08-27 | @ ANA | 129 | W 3-1 | 50-79 | 5 | 41,037 | Brad Bergesen | Trevor Bell | Brad Bergesen | Trevor Bell | Koji Uehara | 476 | 666 | -190 |
| 2010-08-28 | @ ANA | 130 | W 5-0 | 51-79 | 5 | 43,127 | Kevin Millwood | Scott Kazmir | Kevin Millwood | Scott Kazmir | | 481 | 666 | -185 |
| 2010-08-29 | @ ANA | 131 | W 1-0 | 52-79 | 5 | 38,232 | Jeremy Guthrie | Jered Weaver | Jeremy Guthrie | Jered Weaver | Koji Uehara | 482 | 666 | -184 |
| 2010-08-31 | vs BOS | 132 | W 5-2 | 53-79 | 5 | 18,247 | Brian Matusz | Josh Beckett | Brian Matusz | Josh Beckett | Koji Uehara | 487 | 668 | -181 |
| 2010-09-01 | vs BOS | 133 | L 6-9 | 53-80 | 5 | 16,210 | Jake Arrieta | Jon Lester | Jon Lester | Mark Hendrickson | Jonathan Papelbon | 493 | 677 | -184 |
| 2010-09-02 | vs BOS | 134 | L 4-6 | 53-81 | 5 | 26,954 | Brad Bergesen | Daisuke Matsuzaka | Daisuke Matsuzaka | Brad Bergesen | Jonathan Papelbon | 497 | 683 | -186 |
| 2010-09-03 | vs TBA | 135 | L 1-4 | 53-82 | 5 | 13,507 | Kevin Millwood | Matt Garza | Matt Garza | Kevin Millwood | Rafael Soriano | 498 | 687 | -189 |
| 2010-09-04 | vs TBA | 136 | W 8-4 | 54-82 | 6 | 18,943 | Jeremy Guthrie | James Shields | Jeremy Guthrie | James Shields | | 506 | 691 | -185 |
| 2010-09-05 | vs TBA | 137 | W 8-7 | 55-82 | 5 | 28,268 | Chris Tillman | Wade Davis | Alfredo Simon | Dan Wheeler | Koji Uehara | 514 | 698 | -184 |
| 2010-09-06 | @ NYA | 138 | W 4-3 | 56-82 | 5 | 46,103 | Brian Matusz | A.J. Burnett | Brian Matusz | A.J. Burnett | Koji Uehara | 518 | 701 | -183 |
| 2010-09-07 | @ NYA | 139 | W 6-2 | 57-82 | 5 | 46,432 | Jake Arrieta | CC Sabathia | Jake Arrieta | CC Sabathia | | 524 | 703 | -179 |
| 2010-09-08 | @ NYA | 140 | L 2-3 | 57-83 | 5 | 44,163 | Brad Bergesen | Ivan Nova | Joba Chamberlain | Koji Uehara | | 526 | 706 | -180 |
| 2010-09-10 | @ DET | 141 | W 6-3 | 58-83 | 5 | 28,575 | Kevin Millwood | Armando Galarraga | David Hernandez | Phil Coke | Koji Uehara | 532 | 709 | -177 |
| 2010-09-11 | @ DET | 142 | W 5-3 | 59-83 | 5 | 28,139 | Jeremy Guthrie | Max Scherzer | Jeremy Guthrie | Max Scherzer | Koji Uehara | 537 | 712 | -175 |
| 2010-09-12 | @ DET | 143 | L 2-6 | 59-84 | 5 | 24,170 | Chris Tillman | Justin Verlander | Justin Verlander | Mike Gonzalez | | 539 | 718 | -179 |
| 2010-09-13 | vs TOR | 144 | W 4-3 | 60-84 | 5 | 9,882 | Brian Matusz | Marc Rzepczynski | David Hernandez | Brian Tallet | | 543 | 721 | -178 |
| 2010-09-14 | vs TOR | 145 | W 11-3 | 60-85 | 5 | 16,589 | Jake Arrieta | Shawn Hill | Jake Arrieta | Shawn Hill | | 554 | 724 | -170 |
| 2010-09-15 | vs TOR | 146 | W 3-1 | 61-85 | 5 | 13,651 | Brad Bergesen | Kyle Drabek | Brad Bergesen | Kyle Drabek | | 557 | 725 | -168 |
| 2010-09-17 | vs NYA | 147 | L 3-4 | 61-86 | 5 | 32,874 | Kevin Millwood | A.J. Burnett | David Robertson | Koji Uehara | Mariano Rivera | 560 | 729 | -169 |
| 2010-09-18 | vs NYA | 148 | L 3-11 | 62-86 | 5 | 48,775 | Jeremy Guthrie | CC Sabathia | CC Sabathia | Jeremy Guthrie | | 563 | 740 | -177 |
| 2010-09-19 | vs NYA | 149 | W 4-3 | 63-86 | 5 | 39,537 | Chris Tillman | Andy Pettitte | Mike Gonzalez | David Robertson | | 567 | 743 | -176 |
| 2010-09-20 | @ BOS | 150 | W 4-2 | 64-86 | 5 | 37,560 | Brian Matusz | Daisuke Matsuzaka | David Hernandez | Daisuke Matsuzaka | Koji Uehara | 571 | 745 | -174 |
| 2010-09-21 | @ BOS | 151 | W 9-1 | 65-86 | 5 | 37,464 | Brad Bergesen | Clay Buchholz | Brad Bergesen | Scott Atchison | | 580 | 746 | -166 |
| 2010-09-22 | @ BOS | 152 | L 1-6 | 65-87 | 5 | 37,729 | Kevin Millwood | John Lackey | John Lackey | Kevin Millwood | | 581 | 752 | -171 |
| 2010-09-24 | @ TOR | 153 | L 4-6 | 65-88 | 5 | 13,412 | Chris Tillman | Brett Cecil | Brett Cecil | Chris Tillman | Jesse Carlson | 585 | 758 | -173 |
| 2010-09-25 | @ TOR | 154 | L 4-5 | 65-89 | 5 | 21,504 | Jeremy Guthrie | Ricky Romero | David Purcey | Mark Hendrickson | | 589 | 763 | -174 |
| 2010-09-26 | @ TOR | 155 | L 2-5 | 65-90 | 5 | 17,831 | Rick Vanden Hurk | Shaun Marcum | Shaun Marcum | Rick Vanden Hurk | Jason Frasor | 591 | 768 | -177 |
| 2010-09-27 | @ TBA | 156 | W 4-0 | 66-90 | 5 | 12,446 | Brian Matusz | Wade Davis | Brian Matusz | Wade Davis | | 595 | 768 | -173 |
| 2010-09-28 | @ TBA | 157 | L 0-5 | 66-91 | 5 | 17,891 | Brad Bergesen | David Price | David Price | Brad Bergesen | | 595 | 773 | -178 |
| 2010-09-29 | @ TBA | 158 | W 2-0 | 67-91 | 5 | 36,973 | Kevin Millwood | Jeff Niemann | Kevin Millwood | Jeff Niemann | Koji Uehara | 597 | 773 | -176 |
| 2010-10-01 | vs DET | 159 | W 10-6 | 67-92 | 6 | 0 | Chris Tillman | Jeremy Bonderman | Chris Tillman | Jeremy Bonderman | | 607 | 779 | -172 |
| 2010-10-01 | vs DET | 160 | W 2-1 | 67-92 | 6 | 20,870 | Jeremy Guthrie | Rick Porcello | Jeremy Guthrie | Rick Porcello | Koji Uehara | 609 | 780 | -171 |
| 2010-10-02 | vs DET | 161 | W 2-1 | 69-92 | 7 | 35,332 | Brian Matusz | Armando Galarraga | Brian Matusz | Armando Galarraga | Koji Uehara | 611 | 781 | -170 |
| 2010-10-03 | vs DET | 162 | L 2-4 | 69-93 | 5 | 23,914 | Brad Bergesen | Phil Coke | Daniel Schlereth | Brad Bergesen | Jose Valverde | 613 | 785 | -172 |