| 2010-04-05 | vs SEA | 1 | L 3-5 | 0-1 | 4 | 30,686 | Ben Sheets | Felix Hernandez | Brandon League | Brad Ziegler | David Aardsma | 3 | 5 | -2 |
| 2010-04-06 | vs SEA | 2 | W 2-1 | 1-1 | 3 | 10,090 | Dallas Braden | Ian Snell | Edwar Ramirez | Kanekoa Texeira | | 5 | 6 | -1 |
| 2010-04-07 | vs SEA | 3 | W 6-5 | 2-1 | 1 | 18,194 | Justin Duchscherer | Ryan Rowland-Smith | Jerry Blevins | Mark Lowe | | 11 | 11 | 0 |
| 2010-04-08 | vs SEA | 4 | W 6-2 | 3-1 | 1 | 12,464 | Brett Anderson | Doug Fister | Brett Anderson | Doug Fister | | 17 | 13 | 4 |
| 2010-04-09 | @ ANA | 5 | W 10-4 | 3-2 | 1 | 40,034 | Gio Gonzalez | Matt Palmer | Gio Gonzalez | Matt Palmer | | 27 | 17 | 10 |
| 2010-04-10 | @ ANA | 6 | L 3-4 | 3-3 | 2 | 40,249 | Ben Sheets | Jered Weaver | Fernando Rodney | Craig Breslow | | 30 | 21 | 9 |
| 2010-04-11 | @ ANA | 7 | W 9-4 | 4-3 | 1 | 40,601 | Dallas Braden | Joe Saunders | Dallas Braden | Joe Saunders | Tyson Ross | 39 | 25 | 14 |
| 2010-04-12 | @ SEA | 8 | W 4-0 | 5-3 | 1 | 45,876 | Justin Duchscherer | Ryan Rowland-Smith | Justin Duchscherer | Ryan Rowland-Smith | | 43 | 25 | 18 |
| 2010-04-13 | @ SEA | 9 | L 0-3 | 5-4 | 2 | 18,043 | Brett Anderson | Doug Fister | Doug Fister | Brad Ziegler | David Aardsma | 43 | 28 | 15 |
| 2010-04-14 | @ SEA | 10 | L 2-4 | 5-5 | 2 | 15,978 | Gio Gonzalez | Jason Vargas | Jason Vargas | Chad Gaudin | David Aardsma | 45 | 32 | 13 |
| 2010-04-15 | vs BAL | 11 | W 6-2 | 6-5 | 2 | 17,382 | Ben Sheets | David Hernandez | Ben Sheets | David Hernandez | | 51 | 34 | 17 |
| 2010-04-16 | vs BAL | 12 | W 4-2 | 7-5 | 1 | 12,225 | Dallas Braden | Kevin Millwood | Dallas Braden | Kevin Millwood | Andrew Bailey | 55 | 36 | 19 |
| 2010-04-17 | vs BAL | 13 | W 4-3 | 8-5 | 1 | 15,072 | Justin Duchscherer | Jeremy Guthrie | Jerry Blevins | Jim Johnson | | 59 | 39 | 20 |
| 2010-04-18 | vs BAL | 14 | L 3-8 | 8-6 | 1 | 14,451 | Brett Anderson | Brian Matusz | Brian Matusz | Brett Anderson | Jim Johnson | 62 | 47 | 15 |
| 2010-04-20 | vs NYA | 15 | L 3-7 | 8-7 | 2 | 19,849 | Gio Gonzalez | Javier Vazquez | Javier Vazquez | Gio Gonzalez | | 65 | 54 | 11 |
| 2010-04-21 | vs NYA | 16 | L 1-3 | 8-8 | 2 | 30,211 | Ben Sheets | Phil Hughes | Phil Hughes | Ben Sheets | Mariano Rivera | 66 | 57 | 9 |
| 2010-04-22 | vs NYA | 17 | W 4-2 | 9-8 | 2 | 21,986 | Dallas Braden | CC Sabathia | Dallas Braden | CC Sabathia | Andrew Bailey | 70 | 59 | 11 |
| 2010-04-23 | vs CLE | 18 | W 10-0 | 10-8 | 2 | 11,547 | Justin Duchscherer | Jake Westbrook | Justin Duchscherer | Jake Westbrook | | 80 | 59 | 21 |
| 2010-04-24 | vs CLE | 19 | L 1-6 | 10-9 | 2 | 15,873 | Brett Anderson | Fausto Carmona | Fausto Carmona | Chad Gaudin | | 81 | 65 | 16 |
| 2010-04-25 | vs CLE | 20 | W 11-0 | 11-9 | 2 | 16,946 | Gio Gonzalez | Justin Masterson | Gio Gonzalez | Justin Masterson | | 92 | 65 | 27 |
| 2010-04-27 | @ TBA | 21 | L 6-8 | 11-10 | 2 | 10,825 | Ben Sheets | Wade Davis | Wade Davis | Ben Sheets | Rafael Soriano | 98 | 73 | 25 |
| 2010-04-28 | @ TBA | 22 | L 3-10 | 12-10 | 2 | 10,691 | Dallas Braden | James Shields | James Shields | Dallas Braden | | 101 | 83 | 18 |
| 2010-04-29 | @ TOR | 23 | L 3-6 | 12-11 | 2 | 10,721 | Justin Duchscherer | Ricky Romero | Ricky Romero | Justin Duchscherer | Kevin Gregg | 104 | 89 | 15 |
| 2010-04-30 | @ TOR | 24 | L 2-10 | 13-11 | 2 | 12,722 | Trevor Cahill | Brandon Morrow | Brandon Morrow | Trevor Cahill | | 106 | 99 | 7 |
| 2010-05-01 | @ TOR | 25 | W 4-3 | 14-11 | 2 | 13,951 | Gio Gonzalez | Dana Eveland | Gio Gonzalez | Dana Eveland | Andrew Bailey | 110 | 102 | 8 |
| 2010-05-02 | @ TOR | 26 | L 3-9 | 14-12 | 2 | 14,725 | Ben Sheets | Shaun Marcum | Shaun Marcum | Ben Sheets | | 113 | 111 | 2 |
| 2010-05-03 | vs TEX | 27 | L 2-4 | 14-13 | 3 | 8,874 | Dallas Braden | Rich Harden | Rich Harden | Dallas Braden | Neftali Feliz | 115 | 115 | 0 |
| 2010-05-04 | vs TEX | 28 | W 7-6 | 15-13 | 2 | 10,135 | Vin Mazzaro | Scott Feldman | Brad Ziegler | Scott Feldman | Andrew Bailey | 122 | 121 | 1 |
| 2010-05-05 | vs TEX | 29 | W 4-1 | 16-13 | 1 | 15,403 | Trevor Cahill | Colby Lewis | Trevor Cahill | Colby Lewis | Andrew Bailey | 126 | 122 | 4 |
| 2010-05-07 | vs TBA | 30 | L 1-4 | 16-14 | 2 | 19,193 | Gio Gonzalez | David Price | David Price | Gio Gonzalez | Rafael Soriano | 127 | 126 | 1 |
| 2010-05-08 | vs TBA | 31 | W 4-2 | 17-14 | 2 | 15,493 | Ben Sheets | Wade Davis | Ben Sheets | Wade Davis | Andrew Bailey | 131 | 128 | 3 |
| 2010-05-09 | vs TBA | 32 | W 4-0 | 18-14 | 1 | 12,228 | Dallas Braden | James Shields | Dallas Braden | James Shields | | 135 | 128 | 7 |
| 2010-05-11 | @ TEX | 33 | W 7-6 | 19-14 | 1 | 15,474 | Trevor Cahill | Colby Lewis | Tyson Ross | Dustin Nippert | | 142 | 134 | 8 |
| 2010-05-12 | @ TEX | 34 | L 1-10 | 19-15 | 1 | 26,625 | Gio Gonzalez | Derek Holland | Derek Holland | Gio Gonzalez | | 143 | 144 | -1 |
| 2010-05-13 | @ TEX | 35 | L 1-2 | 19-16 | 2 | 27,507 | Ben Sheets | C.J. Wilson | Dustin Nippert | Andrew Bailey | | 144 | 146 | -2 |
| 2010-05-14 | @ ANA | 36 | L 0-4 | 19-17 | 3 | 41,290 | Dallas Braden | Joe Saunders | Joe Saunders | Dallas Braden | | 144 | 150 | -6 |
| 2010-05-15 | @ ANA | 37 | L 3-12 | 20-17 | 1 | 41,744 | Tyson Ross | Ervin Santana | Ervin Santana | Tyson Ross | | 147 | 162 | -15 |
| 2010-05-16 | @ ANA | 38 | L 0-4 | 20-18 | 2 | 41,569 | Trevor Cahill | Joel Pineiro | Joel Pineiro | Trevor Cahill | | 147 | 166 | -19 |
| 2010-05-17 | vs SEA | 39 | W 8-4 | 21-18 | 1 | 10,051 | Gio Gonzalez | Ryan Rowland-Smith | Gio Gonzalez | Ryan Rowland-Smith | | 155 | 170 | -15 |
| 2010-05-18 | vs SEA | 40 | W 6-5 | 22-18 | 1 | 10,512 | Ben Sheets | Felix Hernandez | Craig Breslow | Brandon League | | 161 | 175 | -14 |
| 2010-05-19 | vs DET | 41 | L 1-5 | 22-19 | 2 | 19,284 | Dallas Braden | Justin Verlander | Justin Verlander | Dallas Braden | | 162 | 180 | -18 |
| 2010-05-20 | vs DET | 42 | L 2-5 | 22-20 | 3 | 24,146 | Tyson Ross | Jeremy Bonderman | Jeremy Bonderman | Tyson Ross | Jose Valverde | 164 | 185 | -21 |
| 2010-05-21 | vs SFN | 43 | W 6-1 | 23-20 | 2 | 33,369 | Trevor Cahill | Barry Zito | Trevor Cahill | Barry Zito | | 170 | 186 | -16 |
| 2010-05-22 | vs SFN | 44 | W 1-0 | 24-20 | 1 | 35,067 | Gio Gonzalez | Matt Cain | Gio Gonzalez | Matt Cain | Andrew Bailey | 171 | 186 | -15 |
| 2010-05-23 | vs SFN | 45 | W 3-0 | 25-20 | 1 | 35,067 | Ben Sheets | Jonathan Sanchez | Michael Wuertz | Jonathan Sanchez | Andrew Bailey | 174 | 186 | -12 |
| 2010-05-25 | @ BAL | 46 | L 1-5 | 25-21 | 1 | 14,686 | Dallas Braden | Jeremy Guthrie | Jeremy Guthrie | Tyson Ross | | 175 | 191 | -16 |
| 2010-05-26 | @ BAL | 47 | W 6-1 | 26-21 | 1 | 19,153 | Trevor Cahill | Brian Matusz | Trevor Cahill | Brian Matusz | | 181 | 192 | -11 |
| 2010-05-27 | @ BAL | 48 | W 7-5 | 27-21 | 1 | 26,279 | Gio Gonzalez | Brad Bergesen | Michael Wuertz | Mark Hendrickson | Andrew Bailey | 188 | 197 | -9 |
| 2010-05-28 | @ DET | 49 | W 5-4 | 28-21 | 1 | 40,210 | Ben Sheets | Dontrelle Willis | Brad Ziegler | Ryan Perry | Andrew Bailey | 193 | 201 | -8 |
| 2010-05-29 | @ DET | 50 | W 6-0 | 29-21 | 1 | 39,750 | Brett Anderson | Rick Porcello | Brett Anderson | Rick Porcello | | 199 | 201 | -2 |
| 2010-05-30 | @ DET | 51 | L 2-10 | 30-21 | 1 | 32,510 | Dallas Braden | Max Scherzer | Max Scherzer | Dallas Braden | Joel Zumaya | 201 | 211 | -10 |
| 2010-05-31 | @ DET | 52 | W 4-1 | 31-21 | 1 | 23,641 | Trevor Cahill | Justin Verlander | Trevor Cahill | Justin Verlander | Andrew Bailey | 205 | 212 | -7 |
| 2010-06-01 | @ BOS | 53 | L 4-9 | 31-22 | 1 | 37,337 | Gio Gonzalez | John Lackey | John Lackey | Tyson Ross | | 209 | 221 | -12 |
| 2010-06-02 | @ BOS | 54 | L 4-6 | 31-23 | 1 | 37,783 | Ben Sheets | Daisuke Matsuzaka | Daisuke Matsuzaka | Ben Sheets | Jonathan Papelbon | 213 | 227 | -14 |
| 2010-06-03 | @ BOS | 55 | W 9-8 | 32-23 | 1 | 37,386 | Brett Anderson | Tim Wakefield | Vin Mazzaro | Tim Wakefield | Andrew Bailey | 222 | 235 | -13 |
| 2010-06-04 | vs MIN | 56 | L 4-5 | 32-24 | 1 | 21,703 | Dallas Braden | Scott Baker | Matt Guerrier | Andrew Bailey | Jon Rauch | 226 | 240 | -14 |
| 2010-06-05 | vs MIN | 57 | L 3-4 | 32-25 | 1 | 16,421 | Trevor Cahill | Francisco Liriano | Alex Burnett | Brad Ziegler | Jon Rauch | 229 | 244 | -15 |
| 2010-06-06 | vs MIN | 58 | W 5-4 | 33-25 | 1 | 20,059 | Gio Gonzalez | Nick Blackburn | Gio Gonzalez | Nick Blackburn | Michael Wuertz | 234 | 248 | -14 |
| 2010-06-07 | vs ANA | 59 | L 2-4 | 33-26 | 1 | 10,071 | Ben Sheets | Scott Kazmir | Scott Kazmir | Ben Sheets | Brian Fuentes | 236 | 252 | -16 |
| 2010-06-08 | vs ANA | 60 | W 10-1 | 34-26 | 1 | 11,860 | Vin Mazzaro | Jered Weaver | Vin Mazzaro | Jered Weaver | | 246 | 253 | -7 |
| 2010-06-09 | vs ANA | 61 | L 1-7 | 34-27 | 1 | 18,285 | Dallas Braden | Joe Saunders | Joe Saunders | Dallas Braden | | 247 | 260 | -13 |
| 2010-06-10 | vs ANA | 62 | W 6-1 | 35-27 | 1 | 12,328 | Trevor Cahill | Ervin Santana | Trevor Cahill | Ervin Santana | | 253 | 261 | -8 |
| 2010-06-11 | @ SFN | 63 | L 2-6 | 35-28 | 1 | 41,817 | Gio Gonzalez | Tim Lincecum | Tim Lincecum | Gio Gonzalez | Brian Wilson | 255 | 267 | -12 |
| 2010-06-12 | @ SFN | 64 | L 4-5 | 35-29 | 2 | 36,861 | Ben Sheets | Barry Zito | Barry Zito | Ben Sheets | Brian Wilson | 259 | 272 | -13 |
| 2010-06-13 | @ SFN | 65 | L 2-6 | 35-30 | 2 | 39,187 | Vin Mazzaro | Matt Cain | Matt Cain | Vin Mazzaro | Santiago Casilla | 261 | 278 | -17 |
| 2010-06-15 | @ CHN | 66 | W 9-5 | 36-30 | 2 | 34,390 | Trevor Cahill | Carlos Zambrano | Trevor Cahill | Carlos Zambrano | | 270 | 283 | -13 |
| 2010-06-16 | @ CHN | 67 | L 2-6 | 36-31 | 2 | 36,244 | Gio Gonzalez | Ryan Dempster | Ryan Dempster | Gio Gonzalez | | 272 | 289 | -17 |
| 2010-06-17 | @ CHN | 68 | L 2-3 | 36-32 | 3 | 36,942 | Dallas Braden | Randy Wells | Carlos Marmol | Jerry Blevins | | 274 | 292 | -18 |
| 2010-06-18 | @ SLN | 69 | L 4-6 | 36-33 | 3 | 40,083 | Vin Mazzaro | Chris Carpenter | Chris Carpenter | Brad Ziegler | Ryan Franklin | 278 | 298 | -20 |
| 2010-06-19 | @ SLN | 70 | L 3-4 | 36-34 | 3 | 43,682 | Ben Sheets | Adam Wainwright | Adam Wainwright | Ben Sheets | Jason Motte | 281 | 302 | -21 |
| 2010-06-20 | @ SLN | 71 | W 3-2 | 37-34 | 3 | 42,271 | Trevor Cahill | Jeff Suppan | Craig Breslow | Blake Hawksworth | Andrew Bailey | 284 | 304 | -20 |
| 2010-06-21 | vs CIN | 72 | L 4-6 | 37-35 | 3 | 11,088 | Gio Gonzalez | Mike Leake | Francisco Cordero | Michael Wuertz | Jordan Smith | 288 | 310 | -22 |
| 2010-06-22 | vs CIN | 73 | L 2-4 | 37-36 | 3 | 12,136 | Dallas Braden | Bronson Arroyo | Bronson Arroyo | Dallas Braden | Francisco Cordero | 290 | 314 | -24 |
| 2010-06-23 | vs CIN | 74 | L 0-3 | 37-37 | 3 | 20,824 | Vin Mazzaro | Johnny Cueto | Johnny Cueto | Vin Mazzaro | Francisco Cordero | 290 | 317 | -27 |
| 2010-06-25 | vs PIT | 75 | W 14-4 | 37-38 | 3 | 11,154 | Ben Sheets | Brad Lincoln | Ben Sheets | Brad Lincoln | | 304 | 321 | -17 |
| 2010-06-26 | vs PIT | 76 | W 5-0 | 38-38 | 3 | 25,068 | Trevor Cahill | Daniel McCutchen | Trevor Cahill | Daniel McCutchen | | 309 | 321 | -12 |
| 2010-06-27 | vs PIT | 77 | W 3-2 | 39-38 | 3 | 15,238 | Gio Gonzalez | Ross Ohlendorf | Craig Breslow | Evan Meek | Andrew Bailey | 312 | 323 | -11 |
| 2010-06-29 | @ BAL | 78 | W 4-2 | 40-38 | 3 | 11,987 | Vin Mazzaro | Brian Matusz | Vin Mazzaro | Brian Matusz | Andrew Bailey | 316 | 325 | -9 |
| 2010-06-30 | @ BAL | 79 | L 6-9 | 40-39 | 3 | 21,392 | Ben Sheets | Kevin Millwood | Matt Albers | Cedrick Bowers | Alfredo Simon | 322 | 334 | -12 |
| 2010-07-01 | @ BAL | 80 | W 8-1 | 41-39 | 3 | 15,712 | Trevor Cahill | Jake Arrieta | Trevor Cahill | Jake Arrieta | | 330 | 335 | -5 |
| 2010-07-02 | @ CLE | 81 | W 3-0 | 42-39 | 3 | 18,629 | Gio Gonzalez | Mitch Talbot | Gio Gonzalez | Mitch Talbot | Andrew Bailey | 333 | 335 | -2 |
| 2010-07-03 | @ CLE | 82 | L 4-5 | 42-40 | 3 | 25,483 | Clayton Mortenson | Jake Westbrook | Tony Sipp | Craig Breslow | | 337 | 340 | -3 |
| 2010-07-04 | @ CLE | 83 | W 3-1 | 43-40 | 3 | 13,940 | Vin Mazzaro | Fausto Carmona | Vin Mazzaro | Fausto Carmona | Andrew Bailey | 340 | 341 | -1 |
| 2010-07-05 | vs NYA | 84 | L 1-3 | 43-41 | 3 | 27,405 | Ben Sheets | Javier Vazquez | Javier Vazquez | Ben Sheets | Mariano Rivera | 341 | 344 | -3 |
| 2010-07-06 | vs NYA | 85 | L 1-6 | 43-42 | 3 | 20,473 | Trevor Cahill | CC Sabathia | CC Sabathia | Trevor Cahill | | 342 | 350 | -8 |
| 2010-07-07 | vs NYA | 86 | L 2-6 | 43-43 | 3 | 31,518 | Gio Gonzalez | A.J. Burnett | A.J. Burnett | Gio Gonzalez | | 344 | 356 | -12 |
| 2010-07-09 | vs ANA | 87 | L 5-6 | 43-44 | 3 | 13,156 | Vin Mazzaro | Joel Pineiro | Kevin Jepsen | Andrew Bailey | Brian Fuentes | 349 | 362 | -13 |
| 2010-07-10 | vs ANA | 88 | W 15-1 | 44-44 | 3 | 30,035 | Ben Sheets | Scott Kazmir | Ben Sheets | Scott Kazmir | | 364 | 363 | 1 |
| 2010-07-11 | vs ANA | 89 | W 5-2 | 45-44 | 3 | 15,164 | Trevor Cahill | Jered Weaver | Trevor Cahill | Jered Weaver | Andrew Bailey | 369 | 365 | 4 |
| 2010-07-16 | @ KCA | 90 | W 5-1 | 46-44 | 3 | 37,312 | Gio Gonzalez | Zack Greinke | Gio Gonzalez | Zack Greinke | | 374 | 366 | 8 |
| 2010-07-17 | @ KCA | 91 | W 6-5 | 47-44 | 3 | 26,634 | Trevor Cahill | Bruce Chen | Craig Breslow | Joakim Soria | Andrew Bailey | 380 | 371 | 9 |
| 2010-07-18 | @ KCA | 92 | W 9-6 | 48-44 | 3 | 18,702 | Vin Mazzaro | Brian Bannister | Vin Mazzaro | Brian Bannister | Andrew Bailey | 389 | 377 | 12 |
| 2010-07-19 | vs BOS | 93 | L 1-2 | 48-45 | 3 | 19,341 | Ben Sheets | Daisuke Matsuzaka | Daisuke Matsuzaka | Ben Sheets | Jonathan Papelbon | 390 | 379 | 11 |
| 2010-07-20 | vs BOS | 94 | W 5-4 | 49-45 | 3 | 20,271 | Dallas Braden | Tim Wakefield | Andrew Bailey | Ramon Ramirez | | 395 | 383 | 12 |
| 2010-07-21 | vs BOS | 95 | W 6-4 | 50-45 | 3 | 30,456 | Gio Gonzalez | Clay Buchholz | Gio Gonzalez | Clay Buchholz | Michael Wuertz | 401 | 387 | 14 |
| 2010-07-23 | vs CHA | 96 | L 1-5 | 50-46 | 3 | 15,103 | Trevor Cahill | Mark Buehrle | Mark Buehrle | Trevor Cahill | | 402 | 392 | 10 |
| 2010-07-24 | vs CHA | 97 | W 10-2 | 50-47 | 3 | 17,439 | Vin Mazzaro | Freddy Garcia | Vin Mazzaro | Freddy Garcia | | 412 | 394 | 18 |
| 2010-07-25 | vs CHA | 98 | W 6-4 | 51-47 | 3 | 17,148 | Dallas Braden | Daniel Hudson | Dallas Braden | Daniel Hudson | Michael Wuertz | 418 | 398 | 20 |
| 2010-07-27 | @ TEX | 99 | L 1-3 | 51-48 | 3 | 28,124 | Gio Gonzalez | Cliff Lee | Neftali Feliz | Michael Wuertz | | 419 | 401 | 18 |
| 2010-07-28 | @ TEX | 100 | W 3-1 | 52-48 | 2 | 38,269 | Trevor Cahill | Colby Lewis | Trevor Cahill | Colby Lewis | Craig Breslow | 422 | 402 | 20 |
| 2010-07-29 | @ TEX | 101 | L 4-7 | 52-49 | 3 | 28,793 | Vin Mazzaro | C.J. Wilson | C.J. Wilson | Vin Mazzaro | | 426 | 409 | 17 |
| 2010-07-30 | @ CHA | 102 | L 1-6 | 52-50 | 3 | 29,431 | Brett Anderson | Lucas Harrell | Lucas Harrell | Brett Anderson | | 427 | 415 | 12 |
| 2010-07-31 | @ CHA | 103 | W 6-2 | 53-50 | 3 | 35,852 | Dallas Braden | John Danks | Dallas Braden | John Danks | | 433 | 417 | 16 |
| 2010-08-01 | @ CHA | 104 | L 1-4 | 53-51 | 3 | 32,118 | Gio Gonzalez | Gavin Floyd | Gavin Floyd | Gio Gonzalez | Bobby Jenks | 434 | 421 | 13 |
| 2010-08-02 | vs KCA | 105 | W 6-0 | 54-51 | 3 | 10,047 | Trevor Cahill | Brian Bannister | Trevor Cahill | Brian Bannister | | 440 | 421 | 19 |
| 2010-08-03 | vs KCA | 106 | L 2-3 | 54-52 | 3 | 10,670 | Vin Mazzaro | Kyle Davies | Jesse Chavez | Craig Breslow | Joakim Soria | 442 | 424 | 18 |
| 2010-08-04 | vs KCA | 107 | W 4-3 | 55-52 | 2 | 22,325 | Brett Anderson | Sean O'Sullivan | Brett Anderson | Sean O'Sullivan | Michael Wuertz | 446 | 427 | 19 |
| 2010-08-06 | vs TEX | 108 | L 1-5 | 55-53 | 3 | 26,388 | Dallas Braden | Cliff Lee | Cliff Lee | Dallas Braden | | 447 | 432 | 15 |
| 2010-08-07 | vs TEX | 109 | W 6-2 | 56-53 | 3 | 16,104 | Gio Gonzalez | Rich Harden | Gio Gonzalez | Rich Harden | | 453 | 434 | 19 |
| 2010-08-08 | vs TEX | 110 | W 3-2 | 57-53 | 2 | 18,050 | Trevor Cahill | Colby Lewis | Trevor Cahill | Darren Oliver | Michael Wuertz | 456 | 436 | 20 |
| 2010-08-09 | @ SEA | 111 | L 1-3 | 57-54 | 3 | 19,943 | Vin Mazzaro | Doug Fister | Doug Fister | Vin Mazzaro | David Aardsma | 457 | 439 | 18 |
| 2010-08-10 | @ SEA | 112 | L 0-2 | 57-55 | 3 | 21,377 | Brett Anderson | Felix Hernandez | Felix Hernandez | Brett Anderson | David Aardsma | 457 | 441 | 16 |
| 2010-08-11 | @ SEA | 113 | W 5-1 | 58-55 | 3 | 31,560 | Dallas Braden | Lucas French | Dallas Braden | Lucas French | | 462 | 442 | 20 |
| 2010-08-13 | @ MIN | 114 | L 3-4 | 58-56 | 3 | 40,622 | Gio Gonzalez | Carl Pavano | Carl Pavano | Gio Gonzalez | Matt Capps | 465 | 446 | 19 |
| 2010-08-14 | @ MIN | 115 | L 0-2 | 58-57 | 3 | 40,830 | Trevor Cahill | Brian Duensing | Brian Duensing | Trevor Cahill | | 465 | 448 | 17 |
| 2010-08-15 | @ MIN | 116 | L 2-4 | 58-58 | 3 | 40,602 | Vin Mazzaro | Kevin Slowey | Kevin Slowey | Vin Mazzaro | Matt Capps | 467 | 452 | 15 |
| 2010-08-16 | vs TOR | 117 | L 1-3 | 58-59 | 3 | 10,136 | Brett Anderson | Shaun Marcum | Shaun Marcum | Brett Anderson | | 468 | 455 | 13 |
| 2010-08-17 | vs TOR | 118 | W 6-2 | 59-59 | 3 | 13,237 | Dallas Braden | Brandon Morrow | Dallas Braden | Brian Tallet | Michael Wuertz | 474 | 457 | 17 |
| 2010-08-18 | vs TOR | 119 | W 5-4 | 60-59 | 3 | 18,046 | Gio Gonzalez | Marc Rzepczynski | Brad Ziegler | Casey Janssen | | 479 | 461 | 18 |
| 2010-08-19 | vs TBA | 120 | W 4-3 | 61-59 | 2 | 10,118 | Trevor Cahill | Andy Sonnanstine | Trevor Cahill | Dan Wheeler | Jerry Blevins | 483 | 464 | 19 |
| 2010-08-20 | vs TBA | 121 | W 5-4 | 62-59 | 1 | 13,207 | Vin Mazzaro | Jeremy Hellickson | Henry Rodriguez | Joaquin Benoit | Craig Breslow | 488 | 468 | 20 |
| 2010-08-21 | vs TBA | 122 | L 4-5 | 62-60 | 2 | 16,202 | Brett Anderson | David Price | Randy Choate | Craig Breslow | Rafael Soriano | 492 | 473 | 19 |
| 2010-08-22 | vs TBA | 123 | L 2-3 | 62-61 | 3 | 18,749 | Dallas Braden | Matt Garza | Matt Garza | Dallas Braden | Rafael Soriano | 494 | 476 | 18 |
| 2010-08-24 | @ CLE | 124 | W 5-0 | 63-61 | 3 | 11,751 | Gio Gonzalez | Fausto Carmona | Gio Gonzalez | Fausto Carmona | | 499 | 476 | 23 |
| 2010-08-25 | @ CLE | 125 | W 6-1 | 64-61 | 2 | 10,514 | Trevor Cahill | Mitch Talbot | Trevor Cahill | Mitch Talbot | | 505 | 477 | 28 |
| 2010-08-26 | @ CLE | 126 | L 2-3 | 64-62 | 2 | 11,826 | Vin Mazzaro | Justin Masterson | Justin Masterson | Vin Mazzaro | Chris Perez | 507 | 480 | 27 |
| 2010-08-27 | @ TEX | 127 | L 3-7 | 64-63 | 3 | 34,962 | Brett Anderson | Tommy Hunter | Tommy Hunter | Brett Anderson | | 510 | 487 | 23 |
| 2010-08-28 | @ TEX | 128 | W 5-0 | 65-63 | 2 | 47,411 | Dallas Braden | Rich Harden | Dallas Braden | Rich Harden | | 515 | 487 | 28 |
| 2010-08-29 | @ TEX | 129 | W 8-2 | 66-63 | 2 | 37,188 | Gio Gonzalez | Colby Lewis | Gio Gonzalez | Colby Lewis | | 523 | 489 | 34 |
| 2010-08-30 | @ NYA | 130 | L 5-11 | 67-63 | 2 | 46,356 | Trevor Cahill | Dustin Moseley | Javier Vazquez | Trevor Cahill | | 528 | 500 | 28 |
| 2010-08-31 | @ NYA | 131 | L 3-9 | 67-64 | 2 | 44,575 | Vin Mazzaro | Phil Hughes | Phil Hughes | Vin Mazzaro | | 531 | 509 | 22 |
| 2010-09-01 | @ NYA | 132 | L 3-4 | 67-65 | 2 | 45,222 | Brett Anderson | A.J. Burnett | A.J. Burnett | Brett Anderson | Mariano Rivera | 534 | 513 | 21 |
| 2010-09-02 | @ NYA | 133 | L 0-5 | 67-66 | 2 | 44,644 | Dallas Braden | CC Sabathia | CC Sabathia | Dallas Braden | | 534 | 518 | 16 |
| 2010-09-03 | vs ANA | 134 | W 8-0 | 68-66 | 2 | 23,401 | Gio Gonzalez | Scott Kazmir | Gio Gonzalez | Scott Kazmir | | 542 | 518 | 24 |
| 2010-09-04 | vs ANA | 135 | W 3-1 | 69-66 | 2 | 14,227 | Trevor Cahill | Jered Weaver | Trevor Cahill | Jered Weaver | Andrew Bailey | 545 | 519 | 26 |
| 2010-09-05 | vs ANA | 136 | L 4-7 | 69-67 | 2 | 16,413 | Vin Mazzaro | Ervin Santana | Ervin Santana | Vin Mazzaro | | 549 | 526 | 23 |
| 2010-09-06 | vs SEA | 137 | W 6-2 | 70-67 | 2 | 11,581 | Brett Anderson | Jason Vargas | Brett Anderson | Jason Vargas | | 555 | 528 | 27 |
| 2010-09-07 | vs SEA | 138 | L 5-7 | 70-68 | 2 | 10,067 | Dallas Braden | Doug Fister | Doug Fister | Dallas Braden | David Aardsma | 560 | 535 | 25 |
| 2010-09-08 | vs SEA | 139 | W 4-3 | 71-68 | 2 | 15,180 | Gio Gonzalez | Lucas French | Gio Gonzalez | Lucas French | Andrew Bailey | 564 | 538 | 26 |
| 2010-09-10 | vs BOS | 140 | W 5-0 | 72-68 | 2 | 19,139 | Trevor Cahill | Clay Buchholz | Trevor Cahill | Clay Buchholz | | 569 | 538 | 31 |
| 2010-09-11 | vs BOS | 141 | W 4-3 | 73-68 | 2 | 22,932 | Brett Anderson | John Lackey | Brett Anderson | John Lackey | Andrew Bailey | 573 | 541 | 32 |
| 2010-09-12 | vs BOS | 142 | L 3-5 | 73-69 | 2 | 19,806 | Dallas Braden | Josh Beckett | Josh Beckett | Dallas Braden | Jonathan Papelbon | 576 | 546 | 30 |
| 2010-09-13 | @ KCA | 143 | W 3-1 | 74-69 | 2 | 20,695 | Bobby Cramer | Luke Hochevar | Bobby Cramer | Luke Hochevar | Andrew Bailey | 579 | 547 | 32 |
| 2010-09-14 | @ KCA | 144 | L 3-11 | 75-69 | 2 | 12,852 | Gio Gonzalez | Zack Greinke | Zack Greinke | Gio Gonzalez | | 582 | 558 | 24 |
| 2010-09-15 | @ KCA | 145 | L 3-6 | 75-70 | 2 | 11,087 | Trevor Cahill | Bruce Chen | Bruce Chen | Trevor Cahill | Joakim Soria | 585 | 564 | 21 |
| 2010-09-17 | @ MIN | 146 | W 3-1 | 76-70 | 1 | 40,681 | Brett Anderson | Nick Blackburn | Brett Anderson | Nick Blackburn | Andrew Bailey | 588 | 565 | 23 |
| 2010-09-18 | @ MIN | 147 | L 2-4 | 76-71 | 2 | 40,847 | Dallas Braden | Kevin Slowey | Kevin Slowey | Dallas Braden | Matt Capps | 590 | 569 | 21 |
| 2010-09-19 | @ MIN | 148 | W 6-2 | 77-71 | 1 | 40,088 | Bobby Cramer | Francisco Liriano | Bobby Cramer | Francisco Liriano | | 596 | 571 | 25 |
| 2010-09-20 | vs CHA | 149 | W 3-0 | 78-71 | 1 | 10,090 | Gio Gonzalez | Gavin Floyd | Boof Bonser | Scott Linebrink | Craig Breslow | 599 | 571 | 28 |
| 2010-09-21 | vs CHA | 150 | W 7-2 | 79-71 | 1 | 11,158 | Trevor Cahill | Mark Buehrle | Trevor Cahill | Mark Buehrle | | 606 | 573 | 33 |
| 2010-09-22 | vs CHA | 151 | L 3-4 | 79-72 | 1 | 16,056 | Brett Anderson | Edwin Jackson | Matt Thornton | Brad Ziegler | Chris Sale | 609 | 577 | 32 |
| 2010-09-23 | vs TEX | 152 | W 5-0 | 80-72 | 1 | 10,815 | Dallas Braden | Cliff Lee | Dallas Braden | Cliff Lee | | 614 | 577 | 37 |
| 2010-09-24 | vs TEX | 153 | L 3-10 | 81-72 | 1 | 13,539 | Bobby Cramer | Tommy Hunter | Tommy Hunter | Bobby Cramer | | 617 | 587 | 30 |
| 2010-09-25 | vs TEX | 154 | L 3-4 | 81-73 | 1 | 20,136 | Gio Gonzalez | Derek Holland | Darren O'Day | Michael Wuertz | Neftali Feliz | 620 | 591 | 29 |
| 2010-09-26 | vs TEX | 155 | L 9-16 | 82-73 | 1 | 21,030 | Trevor Cahill | Colby Lewis | Colby Lewis | Trevor Cahill | | 629 | 607 | 22 |
| 2010-09-27 | @ ANA | 156 | L 5-6 | 82-74 | 1 | 40,414 | Brett Anderson | Ervin Santana | Michael Kohn | Brad Ziegler | Fernando Rodney | 634 | 613 | 21 |
| 2010-09-28 | @ ANA | 157 | L 2-4 | 82-75 | 1 | 43,163 | Dallas Braden | Dan Haren | Dan Haren | Dallas Braden | Fernando Rodney | 636 | 617 | 19 |
| 2010-09-29 | @ ANA | 158 | L 1-2 | 82-76 | 1 | 39,199 | Bobby Cramer | Joel Pineiro | Bobby Cassevah | Brad Ziegler | | 637 | 619 | 18 |
| 2010-09-30 | @ SEA | 159 | W 8-1 | 83-76 | 1 | 16,940 | Gio Gonzalez | Doug Fister | Gio Gonzalez | Doug Fister | | 645 | 620 | 25 |
| 2010-10-01 | @ SEA | 160 | W 9-0 | 84-76 | 1 | 19,656 | Trevor Cahill | Lucas French | Trevor Cahill | Lucas French | | 654 | 620 | 34 |
| 2010-10-02 | @ SEA | 161 | W 5-3 | 85-76 | 1 | 17,717 | Brett Anderson | David Pauley | Brett Anderson | David Pauley | Craig Breslow | 659 | 623 | 36 |
| 2010-10-03 | @ SEA | 162 | W 4-3 | 86-76 | 1 | 23,263 | Dallas Braden | Ryan Rowland-Smith | Dallas Braden | Anthony Varvaro | Craig Breslow | 663 | 626 | 37 |