| 2010-04-05 | vs TOR | 1 | W 5-4 | 1-0 | 3 | 50,299 | Scott Feldman | Shaun Marcum | Frank Francisco | Jason Frasor | | 5 | 4 | 1 |
| 2010-04-07 | vs TOR | 2 | L 4-7 | 1-1 | 2 | 22,890 | Rich Harden | Brian Tallet | Brian Tallet | Dustin Nippert | Jason Frasor | 9 | 11 | -2 |
| 2010-04-08 | vs TOR | 3 | L 1-3 | 1-2 | 2 | 14,707 | C.J. Wilson | Ricky Romero | Casey Janssen | Frank Francisco | Jason Frasor | 10 | 14 | -4 |
| 2010-04-09 | vs SEA | 4 | W 6-2 | 2-2 | 2 | 25,271 | Colby Lewis | Jason Vargas | Colby Lewis | Jason Vargas | | 16 | 16 | 0 |
| 2010-04-10 | vs SEA | 5 | L 3-4 | 2-3 | 3 | 26,861 | Matt Harrison | Felix Hernandez | Mark Lowe | Frank Francisco | David Aardsma | 19 | 20 | -1 |
| 2010-04-11 | vs SEA | 6 | W 9-2 | 3-3 | 2 | 26,846 | Scott Feldman | Ian Snell | Scott Feldman | Ian Snell | | 28 | 22 | 6 |
| 2010-04-12 | @ CLE | 7 | W 4-2 | 4-3 | 2 | 42,061 | Rich Harden | Fausto Carmona | Frank Francisco | Jamey Wright | Neftali Feliz | 32 | 24 | 8 |
| 2010-04-14 | @ CLE | 8 | W 6-2 | 5-3 | 1 | 10,071 | Colby Lewis | Justin Masterson | Colby Lewis | Justin Masterson | Neftali Feliz | 38 | 26 | 12 |
| 2010-04-15 | @ CLE | 9 | L 2-3 | 5-4 | 1 | 10,198 | Matt Harrison | David Huff | David Huff | Matt Harrison | | 40 | 29 | 11 |
| 2010-04-16 | @ NYA | 10 | L 1-5 | 5-5 | 2 | 42,145 | C.J. Wilson | CC Sabathia | CC Sabathia | C.J. Wilson | | 41 | 34 | 7 |
| 2010-04-17 | @ NYA | 11 | L 3-7 | 5-6 | 3 | 44,963 | Scott Feldman | A.J. Burnett | A.J. Burnett | Scott Feldman | | 44 | 41 | 3 |
| 2010-04-18 | @ NYA | 12 | L 2-5 | 5-7 | 3 | 44,121 | Rich Harden | Andy Pettitte | Andy Pettitte | Rich Harden | Mariano Rivera | 46 | 46 | 0 |
| 2010-04-20 | @ BOS | 13 | L 6-7 | 5-8 | 4 | 37,614 | Colby Lewis | Tim Wakefield | Jonathan Papelbon | Frank Francisco | | 52 | 53 | -1 |
| 2010-04-21 | @ BOS | 14 | L 7-8 | 5-9 | 4 | 37,518 | Matt Harrison | Josh Beckett | Hideki Okajima | Dustin Nippert | | 59 | 61 | -2 |
| 2010-04-22 | @ BOS | 15 | W 3-0 | 6-9 | 4 | 37,417 | C.J. Wilson | Clay Buchholz | C.J. Wilson | Clay Buchholz | Darren Oliver | 62 | 61 | 1 |
| 2010-04-23 | vs DET | 16 | W 5-4 | 7-9 | 4 | 26,445 | Rich Harden | Max Scherzer | Neftali Feliz | Fu-Te Ni | | 67 | 65 | 2 |
| 2010-04-24 | vs DET | 17 | L 4-8 | 7-10 | 4 | 45,752 | Scott Feldman | Brad Thomas | Eddie Bonine | Scott Feldman | | 71 | 73 | -2 |
| 2010-04-25 | vs DET | 18 | W 8-4 | 8-10 | 3 | 31,211 | Colby Lewis | Rick Porcello | Colby Lewis | Rick Porcello | | 79 | 77 | 2 |
| 2010-04-26 | vs DET | 19 | L 6-8 | 8-11 | 3 | 16,381 | Matt Harrison | Jeremy Bonderman | Phil Coke | Neftali Feliz | Jose Valverde | 85 | 85 | 0 |
| 2010-04-27 | vs CHA | 20 | W 4-2 | 9-11 | 3 | 14,589 | C.J. Wilson | Mark Buehrle | C.J. Wilson | Mark Buehrle | Frank Francisco | 89 | 87 | 2 |
| 2010-04-28 | vs CHA | 21 | W 6-5 | 10-11 | 3 | 20,432 | Rich Harden | Jake Peavy | Rich Harden | Jake Peavy | Neftali Feliz | 95 | 92 | 3 |
| 2010-04-29 | vs CHA | 22 | L 5-7 | 10-12 | 3 | 17,778 | Scott Feldman | Gavin Floyd | Gavin Floyd | Darren O'Day | | 100 | 99 | 1 |
| 2010-04-30 | @ SEA | 23 | W 2-0 | 11-12 | 3 | 34,055 | Colby Lewis | Cliff Lee | Frank Francisco | Brandon League | Neftali Feliz | 102 | 99 | 3 |
| 2010-05-01 | @ SEA | 24 | W 6-3 | 12-12 | 3 | 30,225 | Matt Harrison | Felix Hernandez | Matt Harrison | Felix Hernandez | Frank Francisco | 108 | 102 | 6 |
| 2010-05-02 | @ SEA | 25 | W 3-1 | 13-12 | 3 | 27,185 | C.J. Wilson | Doug Fister | Dustin Nippert | Mark Lowe | Neftali Feliz | 111 | 103 | 8 |
| 2010-05-03 | @ OAK | 26 | W 4-2 | 14-12 | 2 | 8,874 | Rich Harden | Dallas Braden | Rich Harden | Dallas Braden | Neftali Feliz | 115 | 105 | 10 |
| 2010-05-04 | @ OAK | 27 | L 6-7 | 14-13 | 3 | 10,135 | Scott Feldman | Vin Mazzaro | Brad Ziegler | Scott Feldman | Andrew Bailey | 121 | 112 | 9 |
| 2010-05-05 | @ OAK | 28 | L 1-4 | 14-14 | 3 | 15,403 | Colby Lewis | Trevor Cahill | Trevor Cahill | Colby Lewis | Andrew Bailey | 122 | 116 | 6 |
| 2010-05-06 | vs KCA | 29 | W 13-12 | 15-14 | 3 | 15,132 | Matt Harrison | Kyle Davies | Frank Francisco | Joakim Soria | Neftali Feliz | 135 | 128 | 7 |
| 2010-05-07 | vs KCA | 30 | W 4-1 | 16-14 | 3 | 29,065 | C.J. Wilson | Zack Greinke | C.J. Wilson | Zack Greinke | | 139 | 129 | 10 |
| 2010-05-08 | vs KCA | 31 | W 3-2 | 17-14 | 3 | 36,349 | Rich Harden | Gil Meche | Chris Ray | Gil Meche | Neftali Feliz | 142 | 131 | 11 |
| 2010-05-09 | vs KCA | 32 | W 6-4 | 18-14 | 2 | 25,476 | Scott Feldman | Luke Hochevar | Doug Mathis | Brad Thompson | Neftali Feliz | 148 | 135 | 13 |
| 2010-05-11 | vs OAK | 33 | L 6-7 | 18-15 | 2 | 15,474 | Colby Lewis | Trevor Cahill | Tyson Ross | Dustin Nippert | | 154 | 142 | 12 |
| 2010-05-12 | vs OAK | 34 | W 10-1 | 19-15 | 2 | 26,625 | Derek Holland | Gio Gonzalez | Derek Holland | Gio Gonzalez | | 164 | 143 | 21 |
| 2010-05-13 | vs OAK | 35 | W 2-1 | 20-15 | 1 | 27,507 | C.J. Wilson | Ben Sheets | Dustin Nippert | Andrew Bailey | | 166 | 144 | 22 |
| 2010-05-14 | @ TOR | 36 | L 10-16 | 20-16 | 1 | 16,020 | Rich Harden | Brett Cecil | Josh Roenicke | Doug Mathis | | 176 | 160 | 16 |
| 2010-05-15 | @ TOR | 37 | L 0-6 | 20-17 | 2 | 15,945 | Scott Feldman | Ricky Romero | Ricky Romero | Scott Feldman | | 176 | 166 | 10 |
| 2010-05-16 | @ TOR | 38 | L 2-5 | 20-18 | 3 | 25,518 | Colby Lewis | Brandon Morrow | Brandon Morrow | Colby Lewis | Kevin Gregg | 178 | 171 | 7 |
| 2010-05-17 | vs ANA | 39 | W 4-3 | 21-18 | 2 | 20,210 | Derek Holland | Scott Kazmir | Derek Holland | Scott Kazmir | Neftali Feliz | 182 | 174 | 8 |
| 2010-05-18 | vs ANA | 40 | W 8-7 | 22-18 | 2 | 22,358 | C.J. Wilson | Jered Weaver | Darren O'Day | Trevor Bell | Neftali Feliz | 190 | 181 | 9 |
| 2010-05-19 | vs BAL | 41 | W 4-3 | 23-18 | 1 | 22,321 | Rich Harden | Jeremy Guthrie | Frank Francisco | Cla Meredith | | 194 | 184 | 10 |
| 2010-05-20 | vs BAL | 42 | W 13-7 | 23-19 | 1 | 17,304 | Scott Feldman | Brian Matusz | Scott Feldman | Brian Matusz | | 207 | 191 | 16 |
| 2010-05-21 | vs CHN | 43 | W 2-1 | 24-19 | 1 | 38,943 | Colby Lewis | Ted Lilly | Colby Lewis | Ted Lilly | Neftali Feliz | 209 | 192 | 17 |
| 2010-05-22 | vs CHN | 44 | L 4-5 | 24-20 | 2 | 46,180 | Derek Holland | Randy Wells | Sean Marshall | Darren O'Day | Carlos Marmol | 213 | 197 | 16 |
| 2010-05-23 | vs CHN | 45 | L 4-5 | 24-21 | 2 | 37,777 | C.J. Wilson | Carlos Silva | Carlos Silva | C.J. Wilson | Carlos Marmol | 217 | 202 | 15 |
| 2010-05-25 | @ KCA | 46 | W 8-7 | 25-21 | 2 | 12,796 | Rich Harden | Gil Meche | Darren O'Day | Brad Thompson | Neftali Feliz | 225 | 209 | 16 |
| 2010-05-26 | @ KCA | 47 | L 2-5 | 25-22 | 2 | 14,722 | Scott Feldman | Luke Hochevar | Luke Hochevar | Scott Feldman | Joakim Soria | 227 | 214 | 13 |
| 2010-05-28 | @ MIN | 48 | L 1-2 | 25-23 | 2 | 39,581 | Colby Lewis | Kevin Slowey | Kevin Slowey | Colby Lewis | Jon Rauch | 228 | 216 | 12 |
| 2010-05-29 | @ MIN | 49 | L 3-8 | 25-24 | 2 | 39,659 | C.J. Wilson | Carl Pavano | Carl Pavano | C.J. Wilson | | 231 | 224 | 7 |
| 2010-05-30 | @ MIN | 50 | L 3-6 | 25-25 | 3 | 39,873 | Derek Holland | Scott Baker | Scott Baker | Derek Holland | Jon Rauch | 234 | 230 | 4 |
| 2010-06-01 | @ CHA | 51 | W 9-6 | 26-25 | 3 | 20,075 | Rich Harden | Mark Buehrle | Rich Harden | Mark Buehrle | Neftali Feliz | 243 | 236 | 7 |
| 2010-06-02 | @ CHA | 52 | W 9-5 | 27-25 | 3 | 19,516 | Scott Feldman | Gavin Floyd | Scott Feldman | Gavin Floyd | | 252 | 241 | 11 |
| 2010-06-03 | @ CHA | 53 | L 3-4 | 27-26 | 3 | 20,003 | Colby Lewis | Freddy Garcia | Freddy Garcia | Colby Lewis | Bobby Jenks | 255 | 245 | 10 |
| 2010-06-04 | vs TBA | 54 | W 9-6 | 28-26 | 3 | 36,245 | C.J. Wilson | Wade Davis | C.J. Wilson | Wade Davis | Neftali Feliz | 264 | 251 | 13 |
| 2010-06-05 | vs TBA | 55 | W 6-1 | 29-26 | 3 | 25,853 | Tommy Hunter | James Shields | Tommy Hunter | James Shields | | 270 | 252 | 18 |
| 2010-06-06 | vs TBA | 56 | L 5-9 | 29-27 | 3 | 26,932 | Rich Harden | Matt Garza | Matt Garza | Rich Harden | | 275 | 261 | 14 |
| 2010-06-07 | vs SEA | 57 | L 2-4 | 29-28 | 3 | 20,152 | Scott Feldman | Cliff Lee | Cliff Lee | Scott Feldman | | 277 | 265 | 12 |
| 2010-06-08 | vs SEA | 58 | W 7-1 | 30-28 | 3 | 18,774 | Colby Lewis | Felix Hernandez | Colby Lewis | Felix Hernandez | | 284 | 266 | 18 |
| 2010-06-09 | vs SEA | 59 | W 12-2 | 30-29 | 3 | 26,432 | C.J. Wilson | Ian Snell | C.J. Wilson | Ian Snell | | 296 | 268 | 28 |
| 2010-06-10 | vs SEA | 60 | W 12-3 | 30-30 | 3 | 19,674 | Tommy Hunter | Ryan Rowland-Smith | Tommy Hunter | Ryan Rowland-Smith | | 308 | 271 | 37 |
| 2010-06-11 | @ MIL | 61 | L 2-6 | 30-31 | 3 | 33,099 | Rich Harden | Chris Narveson | Chris Narveson | Rich Harden | | 310 | 277 | 33 |
| 2010-06-12 | @ MIL | 62 | W 4-3 | 31-31 | 3 | 39,791 | Scott Feldman | Manny Parra | Scott Feldman | Manny Parra | Chris Ray | 314 | 280 | 34 |
| 2010-06-13 | @ MIL | 63 | W 7-2 | 32-31 | 3 | 36,059 | Colby Lewis | Yovani Gallardo | Colby Lewis | Yovani Gallardo | | 321 | 282 | 39 |
| 2010-06-15 | @ FLO | 64 | W 3-2 | 33-31 | 3 | 17,130 | C.J. Wilson | Josh Johnson | Alexi Ogando | Leo Nunez | Neftali Feliz | 324 | 284 | 40 |
| 2010-06-16 | @ FLO | 65 | W 6-3 | 34-31 | 3 | 17,014 | Tommy Hunter | Anibal Sanchez | Darren O'Day | Anibal Sanchez | Neftali Feliz | 330 | 287 | 43 |
| 2010-06-17 | @ FLO | 66 | W 6-4 | 35-31 | 2 | 11,683 | Dustin Nippert | Ricky Nolasco | Alexi Ogando | Ricky Nolasco | Neftali Feliz | 336 | 291 | 45 |
| 2010-06-18 | @ HOU | 67 | W 9-3 | 36-31 | 2 | 33,951 | Scott Feldman | Wandy Rodriguez | Scott Feldman | Wandy Rodriguez | | 345 | 294 | 51 |
| 2010-06-19 | @ HOU | 68 | W 5-1 | 37-31 | 2 | 41,060 | Colby Lewis | Brian Moehler | Colby Lewis | Brian Moehler | | 350 | 295 | 55 |
| 2010-06-20 | @ HOU | 69 | W 5-4 | 38-31 | 2 | 33,753 | C.J. Wilson | Felipe Paulino | Chris Ray | Casey Daigle | Neftali Feliz | 355 | 299 | 56 |
| 2010-06-22 | vs PIT | 70 | W 6-3 | 39-31 | 2 | 23,083 | Tommy Hunter | Ross Ohlendorf | Tommy Hunter | Ross Ohlendorf | Neftali Feliz | 361 | 302 | 59 |
| 2010-06-23 | vs PIT | 71 | W 13-3 | 39-32 | 2 | 33,646 | Dustin Nippert | Paul Maholm | Alexi Ogando | Paul Maholm | Matt Harrison | 374 | 305 | 69 |
| 2010-06-24 | vs PIT | 72 | W 6-5 | 40-32 | 2 | 19,567 | Scott Feldman | Jeff Karstens | Frank Francisco | Steven Jackson | | 380 | 310 | 70 |
| 2010-06-25 | vs HOU | 73 | L 4-7 | 40-33 | 2 | 43,457 | Colby Lewis | Brian Moehler | Brian Moehler | Colby Lewis | Matt Lindstrom | 384 | 317 | 67 |
| 2010-06-26 | vs HOU | 74 | W 7-2 | 41-33 | 2 | 28,951 | C.J. Wilson | Josh Banks | C.J. Wilson | Josh Banks | | 391 | 319 | 72 |
| 2010-06-27 | vs HOU | 75 | W 10-1 | 42-33 | 2 | 37,487 | Tommy Hunter | Roy Oswalt | Tommy Hunter | Roy Oswalt | | 401 | 320 | 81 |
| 2010-06-29 | @ ANA | 76 | L 5-6 | 42-34 | 2 | 38,514 | Scott Feldman | Joel Pineiro | Joel Pineiro | Scott Feldman | Brian Fuentes | 406 | 326 | 80 |
| 2010-06-30 | @ ANA | 77 | W 6-4 | 43-34 | 2 | 41,867 | Omar Beltre | Scott Kazmir | Dustin Nippert | Scott Kazmir | Neftali Feliz | 412 | 330 | 82 |
| 2010-07-01 | @ ANA | 78 | L 1-2 | 43-35 | 2 | 41,162 | C.J. Wilson | Jered Weaver | Jered Weaver | C.J. Wilson | Brian Fuentes | 413 | 332 | 81 |
| 2010-07-02 | vs CHA | 79 | L 3-5 | 43-36 | 2 | 30,193 | Colby Lewis | Freddy Garcia | J.J. Putz | Neftali Feliz | Matt Thornton | 416 | 337 | 79 |
| 2010-07-03 | vs CHA | 80 | W 3-1 | 44-36 | 2 | 25,986 | Tommy Hunter | John Danks | Tommy Hunter | John Danks | Neftali Feliz | 419 | 338 | 81 |
| 2010-07-04 | vs CHA | 81 | L 3-5 | 44-37 | 2 | 45,020 | Scott Feldman | Mark Buehrle | Mark Buehrle | Scott Feldman | Matt Thornton | 422 | 343 | 79 |
| 2010-07-05 | vs CLE | 82 | L 3-9 | 44-38 | 2 | 25,165 | Omar Beltre | Aaron Laffey | Joe Smith | Omar Beltre | | 425 | 352 | 73 |
| 2010-07-06 | vs CLE | 83 | W 12-1 | 45-38 | 2 | 20,428 | C.J. Wilson | Justin Masterson | C.J. Wilson | Justin Masterson | | 437 | 353 | 84 |
| 2010-07-07 | vs CLE | 84 | W 4-3 | 46-38 | 2 | 24,427 | Colby Lewis | Mitch Talbot | Colby Lewis | Mitch Talbot | Neftali Feliz | 441 | 356 | 85 |
| 2010-07-08 | vs BAL | 85 | L 4-6 | 46-39 | 2 | 16,240 | Tommy Hunter | Jeremy Guthrie | David Hernandez | Frank Francisco | Alfredo Simon | 445 | 362 | 83 |
| 2010-07-09 | vs BAL | 86 | L 6-7 | 46-40 | 2 | 24,216 | Scott Feldman | Brian Matusz | Jason Berken | Dustin Nippert | Alfredo Simon | 451 | 369 | 82 |
| 2010-07-10 | vs BAL | 87 | L 1-6 | 46-41 | 2 | 41,093 | Cliff Lee | Chris Tillman | Chris Tillman | Cliff Lee | | 452 | 375 | 77 |
| 2010-07-11 | vs BAL | 88 | L 1-4 | 46-42 | 2 | 24,566 | C.J. Wilson | Jake Arrieta | Jake Arrieta | C.J. Wilson | Alfredo Simon | 453 | 379 | 74 |
| 2010-07-15 | @ BOS | 89 | W 7-2 | 47-42 | 2 | 38,062 | Tommy Hunter | Tim Wakefield | Tommy Hunter | Tim Wakefield | | 460 | 381 | 79 |
| 2010-07-16 | @ BOS | 90 | W 8-4 | 48-42 | 2 | 37,669 | Colby Lewis | Felix Doubront | Colby Lewis | Felix Doubront | | 468 | 385 | 83 |
| 2010-07-17 | @ BOS | 91 | L 2-3 | 48-43 | 2 | 37,744 | Cliff Lee | John Lackey | Manny Delcarmen | Alexi Ogando | | 470 | 388 | 82 |
| 2010-07-18 | @ BOS | 92 | W 4-2 | 49-43 | 2 | 37,431 | C.J. Wilson | Jon Lester | C.J. Wilson | Jon Lester | Neftali Feliz | 474 | 390 | 84 |
| 2010-07-19 | @ DET | 93 | W 8-6 | 50-43 | 2 | 26,626 | Scott Feldman | Jeremy Bonderman | Matt Harrison | Enrique Gonzalez | Neftali Feliz | 482 | 396 | 86 |
| 2010-07-20 | @ DET | 94 | W 8-0 | 51-43 | 1 | 27,576 | Tommy Hunter | Armando Galarraga | Tommy Hunter | Armando Galarraga | | 490 | 396 | 94 |
| 2010-07-21 | @ DET | 95 | L 1-4 | 51-44 | 2 | 28,704 | Colby Lewis | Max Scherzer | Max Scherzer | Colby Lewis | | 491 | 400 | 91 |
| 2010-07-22 | vs ANA | 96 | W 3-2 | 52-44 | 1 | 39,876 | Cliff Lee | Jered Weaver | Cliff Lee | Jered Weaver | Neftali Feliz | 494 | 402 | 92 |
| 2010-07-23 | vs ANA | 97 | W 1-0 | 53-44 | 1 | 46,554 | C.J. Wilson | Joe Saunders | C.J. Wilson | Joe Saunders | Neftali Feliz | 495 | 402 | 93 |
| 2010-07-24 | vs ANA | 98 | L 2-6 | 53-45 | 1 | 47,098 | Scott Feldman | Ervin Santana | Ervin Santana | Scott Feldman | | 497 | 408 | 89 |
| 2010-07-25 | vs ANA | 99 | W 6-4 | 54-45 | 1 | 38,320 | Tommy Hunter | Trevor Bell | Tommy Hunter | Trevor Bell | Neftali Feliz | 503 | 412 | 91 |
| 2010-07-27 | vs OAK | 100 | W 3-1 | 55-45 | 1 | 28,124 | Cliff Lee | Gio Gonzalez | Neftali Feliz | Michael Wuertz | | 506 | 413 | 93 |
| 2010-07-28 | vs OAK | 101 | L 1-3 | 55-46 | 1 | 38,269 | Colby Lewis | Trevor Cahill | Trevor Cahill | Colby Lewis | Craig Breslow | 507 | 416 | 91 |
| 2010-07-29 | vs OAK | 102 | W 7-4 | 56-46 | 1 | 28,793 | C.J. Wilson | Vin Mazzaro | C.J. Wilson | Vin Mazzaro | | 514 | 420 | 94 |
| 2010-07-30 | @ ANA | 103 | L 7-9 | 56-47 | 1 | 43,024 | Tommy Hunter | Ervin Santana | Ervin Santana | Tommy Hunter | Brian Fuentes | 521 | 429 | 92 |
| 2010-07-31 | @ ANA | 104 | W 2-1 | 57-47 | 1 | 41,011 | Rich Harden | Dan Haren | Rich Harden | Dan Haren | Neftali Feliz | 523 | 430 | 93 |
| 2010-08-01 | @ ANA | 105 | L 1-4 | 57-48 | 1 | 41,019 | Cliff Lee | Jered Weaver | Jered Weaver | Cliff Lee | Brian Fuentes | 524 | 434 | 90 |
| 2010-08-03 | @ SEA | 106 | L 2-3 | 57-49 | 1 | 23,466 | Colby Lewis | Jason Vargas | Jason Vargas | Colby Lewis | David Aardsma | 526 | 437 | 89 |
| 2010-08-04 | @ SEA | 107 | W 11-6 | 57-50 | 1 | 20,174 | C.J. Wilson | Doug Fister | Scott Feldman | Doug Fister | | 537 | 443 | 94 |
| 2010-08-05 | @ SEA | 108 | W 6-0 | 58-50 | 1 | 22,624 | Tommy Hunter | Felix Hernandez | Tommy Hunter | Felix Hernandez | | 543 | 443 | 100 |
| 2010-08-06 | @ OAK | 109 | W 5-1 | 59-50 | 1 | 26,388 | Cliff Lee | Dallas Braden | Cliff Lee | Dallas Braden | | 548 | 444 | 104 |
| 2010-08-07 | @ OAK | 110 | L 2-6 | 59-51 | 1 | 16,104 | Rich Harden | Gio Gonzalez | Gio Gonzalez | Rich Harden | | 550 | 450 | 100 |
| 2010-08-08 | @ OAK | 111 | L 2-3 | 59-52 | 1 | 18,050 | Colby Lewis | Trevor Cahill | Trevor Cahill | Darren Oliver | Michael Wuertz | 552 | 453 | 99 |
| 2010-08-10 | vs NYA | 112 | W 4-3 | 60-52 | 1 | 46,121 | C.J. Wilson | A.J. Burnett | Neftali Feliz | Mariano Rivera | | 556 | 456 | 100 |
| 2010-08-11 | vs NYA | 113 | L 6-7 | 60-53 | 1 | 48,676 | Cliff Lee | Javier Vazquez | Kerry Wood | Neftali Feliz | Mariano Rivera | 562 | 463 | 99 |
| 2010-08-13 | vs BOS | 114 | W 10-9 | 60-54 | 1 | 47,195 | Tommy Hunter | Josh Beckett | Darren O'Day | Tim Wakefield | | 572 | 472 | 100 |
| 2010-08-14 | vs BOS | 115 | L 1-3 | 60-55 | 2 | 48,030 | Colby Lewis | Jon Lester | Jon Lester | Colby Lewis | Felix Doubront | 573 | 475 | 98 |
| 2010-08-15 | vs BOS | 116 | W 7-3 | 61-55 | 1 | 30,252 | C.J. Wilson | Daisuke Matsuzaka | C.J. Wilson | Daisuke Matsuzaka | | 580 | 478 | 102 |
| 2010-08-16 | @ TBA | 117 | L 4-6 | 61-56 | 1 | 18,319 | Cliff Lee | David Price | Lance Cormier | Cliff Lee | Rafael Soriano | 584 | 484 | 100 |
| 2010-08-17 | @ TBA | 118 | L 1-10 | 61-57 | 1 | 18,156 | Tommy Hunter | Matt Garza | Matt Garza | Tommy Hunter | | 585 | 494 | 91 |
| 2010-08-18 | @ TBA | 119 | L 6-8 | 61-58 | 1 | 19,413 | Derek Holland | James Shields | James Shields | Derek Holland | Rafael Soriano | 591 | 502 | 89 |
| 2010-08-19 | @ BAL | 120 | L 0-4 | 61-59 | 3 | 14,635 | Colby Lewis | Brian Matusz | Brian Matusz | Colby Lewis | | 591 | 506 | 85 |
| 2010-08-20 | @ BAL | 121 | W 2-0 | 62-59 | 2 | 18,751 | C.J. Wilson | Jake Arrieta | C.J. Wilson | Jake Arrieta | Neftali Feliz | 593 | 506 | 87 |
| 2010-08-21 | @ BAL | 122 | L 6-8 | 62-60 | 3 | 23,041 | Cliff Lee | Brad Bergesen | Brad Bergesen | Cliff Lee | Koji Uehara | 599 | 514 | 85 |
| 2010-08-22 | @ BAL | 123 | W 6-4 | 63-60 | 1 | 14,788 | Tommy Hunter | Kevin Millwood | Tommy Hunter | Kevin Millwood | Neftali Feliz | 605 | 518 | 87 |
| 2010-08-23 | vs MIN | 124 | W 4-0 | 64-60 | 1 | 22,757 | Rich Harden | Nick Blackburn | Rich Harden | Nick Blackburn | | 609 | 518 | 91 |
| 2010-08-24 | vs MIN | 125 | W 4-3 | 65-60 | 1 | 20,107 | Colby Lewis | Carl Pavano | Darren Oliver | Carl Pavano | Neftali Feliz | 613 | 521 | 92 |
| 2010-08-25 | vs MIN | 126 | W 4-3 | 66-60 | 1 | 29,926 | C.J. Wilson | Brian Duensing | C.J. Wilson | Brian Duensing | Matt Harrison | 617 | 524 | 93 |
| 2010-08-26 | vs MIN | 127 | L 4-6 | 66-61 | 1 | 24,738 | Cliff Lee | Francisco Liriano | Francisco Liriano | Cliff Lee | Matt Capps | 621 | 530 | 91 |
| 2010-08-27 | vs OAK | 128 | W 7-3 | 67-61 | 1 | 34,962 | Tommy Hunter | Brett Anderson | Tommy Hunter | Brett Anderson | | 628 | 533 | 95 |
| 2010-08-28 | vs OAK | 129 | L 0-5 | 67-62 | 1 | 47,411 | Rich Harden | Dallas Braden | Dallas Braden | Rich Harden | | 628 | 538 | 90 |
| 2010-08-29 | vs OAK | 130 | L 2-8 | 67-63 | 1 | 37,188 | Colby Lewis | Gio Gonzalez | Gio Gonzalez | Colby Lewis | | 630 | 546 | 84 |
| 2010-08-30 | @ KCA | 131 | W 3-0 | 68-63 | 1 | 15,881 | C.J. Wilson | Kyle Davies | C.J. Wilson | Kyle Davies | Neftali Feliz | 633 | 546 | 87 |
| 2010-08-31 | @ KCA | 132 | L 9-10 | 69-63 | 1 | 10,295 | Cliff Lee | Sean O'Sullivan | Joakim Soria | Darren Oliver | | 642 | 556 | 86 |
| 2010-09-01 | @ KCA | 133 | W 4-3 | 70-63 | 1 | 10,811 | Tommy Hunter | Bryan Bullington | Tommy Hunter | Bryan Bullington | Neftali Feliz | 646 | 559 | 87 |
| 2010-09-03 | @ MIN | 134 | L 3-4 | 70-64 | 1 | 40,134 | Derek Holland | Matt Fox | Alex Burnett | Derek Holland | Matt Capps | 649 | 563 | 86 |
| 2010-09-04 | @ MIN | 135 | L 4-12 | 71-64 | 1 | 40,496 | Colby Lewis | Carl Pavano | Carl Pavano | Colby Lewis | | 653 | 575 | 78 |
| 2010-09-05 | @ MIN | 136 | L 5-6 | 71-65 | 1 | 40,516 | C.J. Wilson | Nick Blackburn | Nick Blackburn | C.J. Wilson | Matt Capps | 658 | 581 | 77 |
| 2010-09-06 | @ TOR | 137 | L 2-7 | 71-66 | 1 | 17,559 | Tommy Hunter | Ricky Romero | Ricky Romero | Tommy Hunter | | 660 | 588 | 72 |
| 2010-09-07 | @ TOR | 138 | L 5-8 | 71-67 | 1 | 10,518 | Scott Feldman | Shaun Marcum | Shaun Marcum | Scott Feldman | Kevin Gregg | 665 | 596 | 69 |
| 2010-09-08 | @ TOR | 139 | W 8-1 | 72-67 | 1 | 10,616 | Derek Holland | Marc Rzepczynski | Derek Holland | Marc Rzepczynski | | 673 | 597 | 76 |
| 2010-09-09 | @ TOR | 140 | W 4-2 | 73-67 | 1 | 10,658 | Colby Lewis | Shawn Hill | Colby Lewis | Shawn Hill | Neftali Feliz | 677 | 599 | 78 |
| 2010-09-10 | vs NYA | 141 | W 6-5 | 74-67 | 1 | 46,179 | C.J. Wilson | Javier Vazquez | Scott Feldman | Chad Gaudin | | 683 | 604 | 79 |
| 2010-09-11 | vs NYA | 142 | W 7-6 | 75-67 | 1 | 49,210 | Tommy Hunter | A.J. Burnett | Alexi Ogando | Mariano Rivera | | 690 | 610 | 80 |
| 2010-09-12 | vs NYA | 143 | W 4-1 | 76-67 | 1 | 42,007 | Cliff Lee | Dustin Moseley | Cliff Lee | Dustin Moseley | Neftali Feliz | 694 | 611 | 83 |
| 2010-09-14 | vs DET | 144 | W 11-4 | 76-68 | 1 | 24,452 | Derek Holland | Jeremy Bonderman | Dustin Nippert | Robbie Weinhart | | 705 | 615 | 90 |
| 2010-09-15 | vs DET | 145 | W 11-7 | 76-69 | 1 | 34,964 | Colby Lewis | Armando Galarraga | Colby Lewis | Armando Galarraga | | 716 | 622 | 94 |
| 2010-09-17 | @ SEA | 146 | L 1-2 | 76-70 | 2 | 19,302 | C.J. Wilson | Felix Hernandez | Felix Hernandez | C.J. Wilson | David Aardsma | 717 | 624 | 93 |
| 2010-09-18 | @ SEA | 147 | W 6-1 | 77-70 | 1 | 20,843 | Cliff Lee | Jason Vargas | Cliff Lee | Jason Vargas | | 723 | 625 | 98 |
| 2010-09-19 | @ SEA | 148 | L 1-2 | 77-71 | 2 | 20,764 | Tommy Hunter | Doug Fister | Doug Fister | Tommy Hunter | David Aardsma | 724 | 627 | 97 |
| 2010-09-20 | @ ANA | 149 | L 4-7 | 77-72 | 2 | 41,404 | Derek Holland | Jered Weaver | Jered Weaver | Derek Holland | Fernando Rodney | 728 | 634 | 94 |
| 2010-09-21 | @ ANA | 150 | L 0-2 | 77-73 | 2 | 41,707 | Colby Lewis | Ervin Santana | Ervin Santana | Colby Lewis | | 728 | 636 | 92 |
| 2010-09-22 | @ ANA | 151 | W 2-1 | 78-73 | 2 | 41,222 | C.J. Wilson | Dan Haren | Matt Harrison | Matt Palmer | Neftali Feliz | 730 | 637 | 93 |
| 2010-09-23 | @ OAK | 152 | L 0-5 | 78-74 | 2 | 10,815 | Cliff Lee | Dallas Braden | Dallas Braden | Cliff Lee | | 730 | 642 | 88 |
| 2010-09-24 | @ OAK | 153 | W 10-3 | 78-75 | 2 | 13,539 | Tommy Hunter | Bobby Cramer | Tommy Hunter | Bobby Cramer | | 740 | 645 | 95 |
| 2010-09-25 | @ OAK | 154 | W 4-3 | 79-75 | 2 | 20,136 | Derek Holland | Gio Gonzalez | Darren O'Day | Michael Wuertz | Neftali Feliz | 744 | 648 | 96 |
| 2010-09-26 | @ OAK | 155 | W 16-9 | 79-76 | 2 | 21,030 | Colby Lewis | Trevor Cahill | Colby Lewis | Trevor Cahill | | 760 | 657 | 103 |
| 2010-09-27 | vs SEA | 156 | L 5-7 | 79-77 | 2 | 29,381 | C.J. Wilson | David Pauley | David Pauley | C.J. Wilson | Brandon League | 765 | 664 | 101 |
| 2010-09-28 | vs SEA | 157 | L 1-3 | 79-78 | 3 | 26,043 | Scott Feldman | Felix Hernandez | Felix Hernandez | Scott Feldman | Brandon League | 766 | 667 | 99 |
| 2010-09-29 | vs SEA | 158 | W 6-5 | 80-78 | 3 | 23,052 | Rich Harden | Jason Vargas | Neftali Feliz | Dan Cortes | | 772 | 672 | 100 |
| 2010-09-30 | vs ANA | 159 | W 3-2 | 81-78 | 2 | 33,228 | Cliff Lee | Scott Kazmir | Darren O'Day | Jordan Walden | Neftali Feliz | 775 | 674 | 101 |
| 2010-10-01 | vs ANA | 160 | L 4-5 | 81-79 | 3 | 43,149 | Tommy Hunter | Jered Weaver | Rich Thompson | Matt Harrison | Michael Kohn | 779 | 679 | 100 |
| 2010-10-02 | vs ANA | 161 | W 6-2 | 82-79 | 2 | 45,893 | C.J. Wilson | Ervin Santana | C.J. Wilson | Ervin Santana | Neftali Feliz | 785 | 681 | 104 |
| 2010-10-03 | vs ANA | 162 | L 2-6 | 82-80 | 3 | 45,446 | Colby Lewis | Dan Haren | Dan Haren | Dustin Nippert | | 787 | 687 | 100 |