| 2008-03-31 | @ DET | 1 | W 5-4 | 1-0 | 2 | 44,934 | Gil Meche | Justin Verlander | Leo Nunez | Denny Bautista | Joakim Soria | 5 | 4 | 1 |
| 2008-04-02 | @ DET | 2 | W 4-0 | 2-0 | 2 | 32,348 | Brian Bannister | Kenny Rogers | Brian Bannister | Kenny Rogers | | 9 | 4 | 5 |
| 2008-04-03 | @ DET | 3 | W 4-1 | 3-0 | 1 | 32,735 | Zack Greinke | Jeremy Bonderman | Zack Greinke | Jeremy Bonderman | Joakim Soria | 13 | 5 | 8 |
| 2008-04-04 | @ MIN | 4 | L 3-4 | 3-1 | 1 | 21,847 | John Bale | Scott Baker | Scott Baker | John Bale | Joe Nathan | 16 | 9 | 7 |
| 2008-04-05 | @ MIN | 5 | L 4-6 | 3-2 | 2 | 21,262 | Gil Meche | Livan Hernandez | Livan Hernandez | Gil Meche | Joe Nathan | 20 | 15 | 5 |
| 2008-04-06 | @ MIN | 6 | W 3-1 | 4-2 | 2 | 21,765 | Brett Tomko | Boof Bonser | Brett Tomko | Boof Bonser | Joakim Soria | 23 | 16 | 7 |
| 2008-04-08 | vs NYA | 7 | W 5-2 | 5-2 | 2 | 37,296 | Brian Bannister | Phil Hughes | Brian Bannister | Phil Hughes | Joakim Soria | 28 | 18 | 10 |
| 2008-04-09 | vs NYA | 8 | W 4-0 | 6-2 | 1 | 19,007 | Zack Greinke | Brian Bruney | Zack Greinke | Kyle Farnsworth | Jimmy Gobble | 32 | 18 | 14 |
| 2008-04-10 | vs NYA | 9 | L 1-6 | 6-3 | 1 | 16,143 | John Bale | Andy Pettitte | Andy Pettitte | John Bale | | 33 | 24 | 9 |
| 2008-04-11 | vs MIN | 10 | L 0-5 | 6-4 | 1 | 16,691 | Gil Meche | Livan Hernandez | Livan Hernandez | Gil Meche | | 33 | 29 | 4 |
| 2008-04-12 | vs MIN | 11 | L 0-2 | 6-5 | 2 | 36,300 | Brett Tomko | Boof Bonser | Boof Bonser | Brett Tomko | Joe Nathan | 33 | 31 | 2 |
| 2008-04-13 | vs MIN | 12 | W 5-1 | 7-5 | 2 | 13,886 | Brian Bannister | Francisco Liriano | Brian Bannister | Francisco Liriano | | 38 | 32 | 6 |
| 2008-04-14 | @ SEA | 13 | W 5-1 | 8-5 | 1 | 16,751 | Zack Greinke | Jarrod Washburn | Zack Greinke | Jarrod Washburn | | 43 | 33 | 10 |
| 2008-04-15 | @ SEA | 14 | L 6-11 | 8-6 | 2 | 17,137 | John Bale | Miguel Batista | Miguel Batista | John Bale | | 49 | 44 | 5 |
| 2008-04-16 | @ ANA | 15 | W 3-2 | 9-6 | 2 | 41,336 | Gil Meche | Jered Weaver | Gil Meche | Jered Weaver | Joakim Soria | 52 | 46 | 6 |
| 2008-04-17 | @ ANA | 16 | L 3-5 | 9-7 | 2 | 40,021 | Brett Tomko | Jon Garland | Jon Garland | Brett Tomko | Francisco Rodriguez | 55 | 51 | 4 |
| 2008-04-18 | @ OAK | 17 | L 2-13 | 9-8 | 2 | 12,528 | Brian Bannister | Chad Gaudin | Chad Gaudin | Brian Bannister | | 57 | 64 | -7 |
| 2008-04-19 | @ OAK | 18 | L 5-6 | 9-9 | 2 | 20,390 | Zack Greinke | Greg Smith | Joey Devine | Joel Peralta | Huston Street | 62 | 70 | -8 |
| 2008-04-20 | @ OAK | 19 | L 1-7 | 9-10 | 2 | 18,645 | Luke Hochevar | Dana Eveland | Dana Eveland | Luke Hochevar | | 63 | 77 | -14 |
| 2008-04-22 | vs CLE | 20 | L 1-15 | 9-11 | 3 | 16,165 | Gil Meche | CC Sabathia | CC Sabathia | Gil Meche | | 64 | 92 | -28 |
| 2008-04-24 | vs CLE | 21 | L 6-9 | 9-13 | 5 | 0 | Brett Tomko | Fausto Carmona | Fausto Carmona | Brett Tomko | Rafael Betancourt | 70 | 101 | -31 |
| 2008-04-24 | vs CLE | 22 | L 0-2 | 9-13 | 5 | 11,637 | Brian Bannister | Cliff Lee | Cliff Lee | Brian Bannister | | 70 | 103 | -33 |
| 2008-04-25 | vs TOR | 23 | W 8-4 | 10-13 | 3 | 22,561 | Zack Greinke | A.J. Burnett | Leo Nunez | A.J. Burnett | | 78 | 107 | -29 |
| 2008-04-26 | vs TOR | 24 | W 2-1 | 11-13 | 3 | 24,078 | Luke Hochevar | Shaun Marcum | Luke Hochevar | Shaun Marcum | Joakim Soria | 80 | 108 | -28 |
| 2008-04-27 | vs TOR | 25 | L 2-5 | 11-14 | 3 | 13,998 | Gil Meche | Jesse Litsch | Jesse Litsch | Gil Meche | Jesse Carlson | 82 | 113 | -31 |
| 2008-04-29 | @ TEX | 26 | W 9-5 | 12-14 | 2 | 16,472 | Brett Tomko | Jason Jennings | Ron Mahay | Jason Jennings | | 91 | 118 | -27 |
| 2008-04-30 | @ TEX | 27 | L 9-11 | 12-15 | 5 | 17,705 | Brian Bannister | Kevin Millwood | Kevin Millwood | Brian Bannister | | 100 | 129 | -29 |
| 2008-05-01 | @ TEX | 28 | L 1-2 | 12-16 | 5 | 14,563 | Zack Greinke | Sidney Ponson | Sidney Ponson | Zack Greinke | C.J. Wilson | 101 | 131 | -30 |
| 2008-05-03 | @ CLE | 29 | W 4-2 | 13-16 | 5 | 27,272 | Luke Hochevar | CC Sabathia | Luke Hochevar | CC Sabathia | Joakim Soria | 105 | 133 | -28 |
| 2008-05-04 | @ CLE | 30 | W 2-0 | 14-16 | 3 | 27,836 | Gil Meche | Aaron Laffey | Gil Meche | Aaron Laffey | Joakim Soria | 107 | 133 | -26 |
| 2008-05-05 | vs ANA | 31 | L 0-4 | 14-17 | 4 | 12,157 | Brett Tomko | Ervin Santana | Ervin Santana | Ramon Ramirez | | 107 | 137 | -30 |
| 2008-05-06 | vs ANA | 32 | L 3-5 | 14-18 | 4 | 11,354 | Brian Bannister | Nick Adenhart | Darren Oliver | Brian Bannister | Francisco Rodriguez | 110 | 142 | -32 |
| 2008-05-07 | vs ANA | 33 | W 9-4 | 15-18 | 4 | 11,084 | Zack Greinke | Jered Weaver | Zack Greinke | Jered Weaver | | 119 | 146 | -27 |
| 2008-05-08 | vs BAL | 34 | L 1-4 | 15-19 | 4 | 11,781 | Luke Hochevar | Daniel Cabrera | Daniel Cabrera | Luke Hochevar | | 120 | 150 | -30 |
| 2008-05-09 | vs BAL | 35 | L 4-7 | 15-20 | 5 | 21,873 | Gil Meche | Steve Trachsel | Steve Trachsel | Gil Meche | George Sherrill | 124 | 157 | -33 |
| 2008-05-10 | vs BAL | 36 | L 5-6 | 15-21 | 5 | 15,808 | Brett Tomko | Garrett Olson | Garrett Olson | Brett Tomko | George Sherrill | 129 | 163 | -34 |
| 2008-05-11 | vs BAL | 37 | W 4-0 | 16-21 | 4 | 18,635 | Brian Bannister | Brian Burres | Brian Bannister | Brian Burres | | 133 | 163 | -30 |
| 2008-05-13 | vs DET | 38 | W 3-2 | 17-21 | 4 | 11,703 | Zack Greinke | Nate Robertson | Leo Nunez | Francisco Cruceta | Joakim Soria | 136 | 165 | -29 |
| 2008-05-14 | vs DET | 39 | W 2-0 | 18-21 | 4 | 14,053 | Luke Hochevar | Justin Verlander | Luke Hochevar | Justin Verlander | Joakim Soria | 138 | 165 | -27 |
| 2008-05-15 | vs DET | 40 | W 8-4 | 19-21 | 4 | 34,734 | Gil Meche | Kenny Rogers | Gil Meche | Kenny Rogers | | 146 | 169 | -23 |
| 2008-05-16 | @ FLO | 41 | W 7-6 | 20-21 | 4 | 14,825 | Brett Tomko | Andrew Miller | Brett Tomko | Andrew Miller | Joakim Soria | 153 | 175 | -22 |
| 2008-05-17 | @ FLO | 42 | L 3-7 | 20-22 | 4 | 16,214 | Brian Bannister | Scott Olsen | Logan Kensing | Brian Bannister | | 156 | 182 | -26 |
| 2008-05-18 | @ FLO | 43 | W 9-3 | 21-22 | 3 | 10,617 | Zack Greinke | Burke Badenhop | Zack Greinke | Burke Badenhop | | 165 | 185 | -20 |
| 2008-05-19 | @ BOS | 44 | L 0-7 | 21-23 | 4 | 37,746 | Luke Hochevar | Jon Lester | Jon Lester | Luke Hochevar | | 165 | 192 | -27 |
| 2008-05-20 | @ BOS | 45 | L 1-2 | 21-24 | 4 | 37,486 | Gil Meche | Justin Masterson | Justin Masterson | Gil Meche | Jonathan Papelbon | 166 | 194 | -28 |
| 2008-05-21 | @ BOS | 46 | L 3-6 | 21-25 | 4 | 37,674 | Brett Tomko | Bartolo Colon | Bartolo Colon | Brett Tomko | | 169 | 200 | -31 |
| 2008-05-22 | @ BOS | 47 | L 8-11 | 21-26 | 4 | 37,613 | Brian Bannister | Daisuke Matsuzaka | Daisuke Matsuzaka | Brian Bannister | Jonathan Papelbon | 177 | 211 | -34 |
| 2008-05-23 | @ TOR | 48 | L 1-7 | 21-27 | 4 | 24,207 | Zack Greinke | Roy Halladay | Roy Halladay | Zack Greinke | | 178 | 218 | -40 |
| 2008-05-24 | @ TOR | 49 | L 0-6 | 21-28 | 5 | 28,162 | Luke Hochevar | Jesse Litsch | Jesse Litsch | Luke Hochevar | | 178 | 224 | -46 |
| 2008-05-25 | @ TOR | 50 | L 1-3 | 21-29 | 5 | 29,315 | Gil Meche | Dustin McGowan | Dustin McGowan | Gil Meche | B.J. Ryan | 179 | 227 | -48 |
| 2008-05-26 | @ TOR | 51 | L 2-7 | 21-30 | 5 | 23,157 | Brett Tomko | Shaun Marcum | Shaun Marcum | Brett Tomko | | 181 | 234 | -53 |
| 2008-05-27 | vs MIN | 52 | L 3-4 | 21-31 | 5 | 17,191 | Brian Bannister | Nick Blackburn | Jesse Crain | Leo Nunez | Matt Guerrier | 184 | 238 | -54 |
| 2008-05-28 | vs MIN | 53 | L 8-9 | 21-32 | 5 | 13,621 | Zack Greinke | Livan Hernandez | Jesse Crain | Joel Peralta | Joe Nathan | 192 | 247 | -55 |
| 2008-05-29 | vs MIN | 54 | L 1-5 | 21-33 | 5 | 12,336 | Luke Hochevar | Kevin Slowey | Kevin Slowey | Luke Hochevar | | 193 | 252 | -59 |
| 2008-05-30 | vs CLE | 55 | L 4-5 | 21-34 | 5 | 25,243 | Gil Meche | Cliff Lee | Cliff Lee | Brett Tomko | Joe Borowski | 197 | 257 | -60 |
| 2008-05-31 | vs CLE | 56 | W 4-2 | 22-34 | 5 | 23,923 | Kyle Davies | CC Sabathia | Kyle Davies | CC Sabathia | Joakim Soria | 201 | 259 | -58 |
| 2008-06-01 | vs CLE | 57 | W 6-1 | 23-34 | 5 | 22,345 | Brian Bannister | Paul Byrd | Brian Bannister | Paul Byrd | | 207 | 260 | -53 |
| 2008-06-03 | @ CHA | 58 | L 5-9 | 23-35 | 5 | 21,727 | Zack Greinke | Gavin Floyd | Gavin Floyd | Zack Greinke | | 212 | 269 | -57 |
| 2008-06-04 | @ CHA | 59 | L 4-6 | 23-36 | 5 | 23,515 | Luke Hochevar | John Danks | Octavio Dotel | Jimmy Gobble | | 216 | 275 | -59 |
| 2008-06-05 | @ CHA | 60 | L 2-6 | 23-37 | 5 | 25,104 | Gil Meche | Jose Contreras | Jose Contreras | Gil Meche | | 218 | 281 | -63 |
| 2008-06-06 | @ NYA | 61 | W 2-1 | 24-37 | 5 | 52,187 | Kyle Davies | Darrell Rasner | Kyle Davies | Darrell Rasner | Joakim Soria | 220 | 282 | -62 |
| 2008-06-07 | @ NYA | 62 | L 11-12 | 24-38 | 5 | 53,611 | Brian Bannister | Andy Pettitte | Mariano Rivera | Joakim Soria | | 231 | 294 | -63 |
| 2008-06-08 | @ NYA | 63 | L 3-6 | 24-39 | 5 | 54,213 | Zack Greinke | Joba Chamberlain | Dan Giese | Zack Greinke | Mariano Rivera | 234 | 300 | -66 |
| 2008-06-09 | @ NYA | 64 | W 3-2 | 25-39 | 5 | 53,633 | Luke Hochevar | Mike Mussina | Yasuhiko Yabuta | Mariano Rivera | Joakim Soria | 237 | 302 | -65 |
| 2008-06-10 | vs TEX | 65 | L 5-6 | 25-40 | 5 | 14,741 | Gil Meche | Kevin Millwood | Eddie Guardado | Yasuhiko Yabuta | C.J. Wilson | 242 | 308 | -66 |
| 2008-06-11 | vs TEX | 66 | L 5-11 | 25-41 | 5 | 20,840 | Kyle Davies | Vicente Padilla | Vicente Padilla | Jimmy Gobble | | 247 | 319 | -72 |
| 2008-06-12 | vs TEX | 67 | W 6-5 | 26-41 | 5 | 15,515 | Brian Bannister | Eric Hurley | Ron Mahay | Frank Francisco | Joakim Soria | 253 | 324 | -71 |
| 2008-06-13 | @ ARI | 68 | L 0-1 | 26-42 | 5 | 33,323 | Zack Greinke | Doug Davis | Billy Buckner | Yasuhiko Yabuta | | 253 | 325 | -72 |
| 2008-06-14 | @ ARI | 69 | W 12-3 | 27-42 | 5 | 44,615 | Luke Hochevar | Randy Johnson | Luke Hochevar | Randy Johnson | | 265 | 328 | -63 |
| 2008-06-15 | @ ARI | 70 | W 8-3 | 28-42 | 5 | 39,125 | Gil Meche | Micah Owings | Gil Meche | Micah Owings | | 273 | 331 | -58 |
| 2008-06-17 | @ SLN | 71 | W 2-1 | 29-42 | 5 | 43,793 | Kyle Davies | Joel Pineiro | Kyle Davies | Ron Villone | Joakim Soria | 275 | 332 | -57 |
| 2008-06-18 | @ SLN | 72 | W 3-2 | 30-42 | 5 | 43,810 | Brian Bannister | Braden Looper | Brian Bannister | Kyle McClellan | Joakim Soria | 278 | 334 | -56 |
| 2008-06-19 | @ SLN | 73 | W 4-1 | 31-42 | 5 | 44,277 | Zack Greinke | Brad Thompson | Zack Greinke | Brad Thompson | Joakim Soria | 282 | 335 | -53 |
| 2008-06-20 | vs SFN | 74 | L 4-9 | 31-43 | 5 | 34,588 | Luke Hochevar | Matt Cain | Matt Cain | Yasuhiko Yabuta | | 286 | 344 | -58 |
| 2008-06-21 | vs SFN | 75 | W 5-3 | 32-43 | 5 | 28,903 | Gil Meche | Kevin Correia | Gil Meche | Kevin Correia | Joakim Soria | 291 | 347 | -56 |
| 2008-06-22 | vs SFN | 76 | W 11-10 | 33-43 | 5 | 20,499 | Kyle Davies | Tim Lincecum | Ron Mahay | Alex Hinshaw | Joakim Soria | 302 | 357 | -55 |
| 2008-06-23 | vs COL | 77 | W 8-4 | 34-43 | 5 | 12,260 | Brian Bannister | Jeff Francis | Brian Bannister | Jeff Francis | | 310 | 361 | -51 |
| 2008-06-24 | vs COL | 78 | W 7-3 | 35-43 | 5 | 19,169 | Zack Greinke | Jorge de la Rosa | Zack Greinke | Jorge de la Rosa | | 317 | 364 | -47 |
| 2008-06-25 | vs COL | 79 | W 4-2 | 36-43 | 4 | 16,615 | Luke Hochevar | Aaron Cook | Luke Hochevar | Aaron Cook | Joakim Soria | 321 | 366 | -45 |
| 2008-06-27 | vs SLN | 80 | W 7-2 | 37-43 | 5 | 36,360 | Gil Meche | Joel Pineiro | Gil Meche | Joel Pineiro | | 328 | 368 | -40 |
| 2008-06-28 | vs SLN | 81 | L 1-5 | 37-44 | 5 | 37,537 | Kyle Davies | Mitchell Boggs | Mitchell Boggs | Kyle Davies | | 329 | 373 | -44 |
| 2008-06-29 | vs SLN | 82 | L 6-9 | 37-45 | 5 | 31,803 | Brian Bannister | Braden Looper | Chris Perez | Brian Bannister | Ryan Franklin | 335 | 382 | -47 |
| 2008-06-30 | @ BAL | 83 | W 6-5 | 38-45 | 4 | 15,289 | Zack Greinke | Brian Burres | Ron Mahay | Chad Bradford | Joakim Soria | 341 | 387 | -46 |
| 2008-07-01 | @ BAL | 84 | L 5-7 | 38-46 | 4 | 19,756 | Luke Hochevar | Radhames Liz | Radhames Liz | Luke Hochevar | George Sherrill | 346 | 394 | -48 |
| 2008-07-02 | @ BAL | 85 | L 2-5 | 38-47 | 4 | 17,909 | Gil Meche | Daniel Cabrera | Daniel Cabrera | Gil Meche | | 348 | 399 | -51 |
| 2008-07-03 | @ BAL | 86 | W 10-7 | 39-47 | 4 | 16,782 | Kyle Davies | Garrett Olson | Joel Peralta | Adam Loewen | Joakim Soria | 358 | 406 | -48 |
| 2008-07-04 | @ TBA | 87 | L 2-11 | 39-48 | 4 | 16,830 | Brian Bannister | Edwin Jackson | Edwin Jackson | Brian Bannister | | 360 | 417 | -57 |
| 2008-07-05 | @ TBA | 88 | L 0-3 | 39-49 | 4 | 30,418 | Zack Greinke | Andy Sonnanstine | Andy Sonnanstine | Zack Greinke | Grant Balfour | 360 | 420 | -60 |
| 2008-07-06 | @ TBA | 89 | L 2-9 | 39-50 | 4 | 20,587 | Luke Hochevar | James Shields | James Shields | Luke Hochevar | | 362 | 429 | -67 |
| 2008-07-07 | @ TBA | 90 | W 7-4 | 40-50 | 4 | 16,293 | Gil Meche | Matt Garza | Joakim Soria | Dan Wheeler | | 369 | 433 | -64 |
| 2008-07-08 | vs CHA | 91 | L 7-8 | 40-51 | 4 | 13,614 | Kyle Davies | Jose Contreras | Nick Masset | Rob Tejeda | | 376 | 441 | -65 |
| 2008-07-09 | vs CHA | 92 | L 6-7 | 40-52 | 4 | 16,502 | Brian Bannister | Javier Vazquez | Adam Russell | Rob Tejeda | Octavio Dotel | 382 | 448 | -66 |
| 2008-07-10 | vs CHA | 93 | W 4-1 | 41-52 | 4 | 14,547 | Zack Greinke | Mark Buehrle | Ron Mahay | Mark Buehrle | Joakim Soria | 386 | 449 | -63 |
| 2008-07-11 | vs SEA | 94 | W 3-1 | 42-52 | 4 | 25,345 | Luke Hochevar | Felix Hernandez | Luke Hochevar | Felix Hernandez | Joakim Soria | 389 | 450 | -61 |
| 2008-07-12 | vs SEA | 95 | W 5-4 | 43-52 | 4 | 23,792 | Gil Meche | Jarrod Washburn | Horacio Ramirez | Brandon Morrow | | 394 | 454 | -60 |
| 2008-07-13 | vs SEA | 96 | L 3-4 | 43-53 | 4 | 21,421 | Kyle Davies | Carlos Silva | Sean Green | Joakim Soria | Brandon Morrow | 397 | 458 | -61 |
| 2008-07-18 | @ CHA | 97 | L 5-9 | 43-54 | 4 | 36,291 | Zack Greinke | Mark Buehrle | Mark Buehrle | Zack Greinke | | 402 | 467 | -65 |
| 2008-07-19 | @ CHA | 98 | W 9-1 | 44-54 | 4 | 36,566 | Gil Meche | Gavin Floyd | Gil Meche | Gavin Floyd | | 411 | 468 | -57 |
| 2008-07-20 | @ CHA | 99 | W 8-7 | 45-54 | 4 | 32,269 | Brian Bannister | John Danks | Ramon Ramirez | Matt Thornton | Joakim Soria | 419 | 475 | -56 |
| 2008-07-21 | vs DET | 100 | L 4-19 | 45-55 | 4 | 14,137 | Luke Hochevar | Zach Miner | Zach Miner | Luke Hochevar | | 423 | 494 | -71 |
| 2008-07-22 | vs DET | 101 | L 1-7 | 45-56 | 4 | 22,074 | Kyle Davies | Kenny Rogers | Kenny Rogers | Kyle Davies | | 424 | 501 | -77 |
| 2008-07-23 | vs DET | 102 | L 1-7 | 45-57 | 4 | 16,594 | Zack Greinke | Armando Galarraga | Armando Galarraga | Zack Greinke | | 425 | 508 | -83 |
| 2008-07-24 | vs TBA | 103 | W 4-2 | 46-57 | 4 | 25,900 | Gil Meche | Matt Garza | Gil Meche | Matt Garza | Joakim Soria | 429 | 510 | -81 |
| 2008-07-25 | vs TBA | 104 | L 3-5 | 46-58 | 5 | 31,535 | Brian Bannister | Edwin Jackson | Edwin Jackson | Brian Bannister | Troy Percival | 432 | 515 | -83 |
| 2008-07-26 | vs TBA | 105 | L 3-5 | 46-59 | 5 | 24,322 | Luke Hochevar | Scott Kazmir | Alberto Reyes | Horacio Ramirez | Troy Percival | 435 | 520 | -85 |
| 2008-07-27 | vs TBA | 106 | W 6-1 | 47-59 | 4 | 13,779 | Kyle Davies | Andy Sonnanstine | Kyle Davies | Andy Sonnanstine | | 441 | 521 | -80 |
| 2008-07-28 | @ OAK | 107 | W 4-2 | 48-59 | 4 | 12,464 | Zack Greinke | Dallas Braden | Zack Greinke | Dallas Braden | Joakim Soria | 445 | 523 | -78 |
| 2008-07-29 | @ OAK | 108 | W 5-2 | 49-59 | 4 | 12,182 | Gil Meche | Greg Smith | Gil Meche | Greg Smith | Joakim Soria | 450 | 525 | -75 |
| 2008-07-30 | @ OAK | 109 | W 4-3 | 50-59 | 4 | 26,272 | Brian Bannister | Sean Gallagher | Ramon Ramirez | Huston Street | Joakim Soria | 454 | 528 | -74 |
| 2008-08-01 | vs CHA | 110 | L 2-4 | 50-60 | 4 | 21,291 | Luke Hochevar | Javier Vazquez | Javier Vazquez | Luke Hochevar | Bobby Jenks | 456 | 532 | -76 |
| 2008-08-02 | vs CHA | 111 | W 9-7 | 51-60 | 4 | 21,866 | Kyle Davies | Mark Buehrle | Kyle Davies | Mark Buehrle | Joakim Soria | 465 | 539 | -74 |
| 2008-08-03 | vs CHA | 112 | W 14-3 | 52-60 | 4 | 15,268 | Zack Greinke | Clayton Richard | Zack Greinke | Clayton Richard | | 479 | 542 | -63 |
| 2008-08-04 | vs BOS | 113 | W 4-3 | 53-60 | 4 | 24,378 | Gil Meche | Clay Buchholz | Gil Meche | Clay Buchholz | Joakim Soria | 483 | 545 | -62 |
| 2008-08-05 | vs BOS | 114 | L 2-8 | 53-61 | 4 | 22,069 | Brian Bannister | Josh Beckett | Josh Beckett | Brian Bannister | | 485 | 553 | -68 |
| 2008-08-06 | vs BOS | 115 | L 2-8 | 53-62 | 4 | 24,294 | Luke Hochevar | Tim Wakefield | Tim Wakefield | Luke Hochevar | | 487 | 561 | -74 |
| 2008-08-08 | vs MIN | 116 | L 1-4 | 53-63 | 4 | 33,653 | Kyle Davies | Kevin Slowey | Kevin Slowey | Kyle Davies | Joe Nathan | 488 | 565 | -77 |
| 2008-08-09 | vs MIN | 117 | L 3-7 | 53-64 | 4 | 27,960 | Zack Greinke | Francisco Liriano | Francisco Liriano | Zack Greinke | | 491 | 572 | -81 |
| 2008-08-10 | vs MIN | 118 | W 5-4 | 54-64 | 4 | 23,163 | Gil Meche | Scott Baker | Rob Tejeda | Craig Breslow | | 496 | 576 | -80 |
| 2008-08-12 | @ CHA | 119 | L 0-9 | 54-65 | 5 | 31,099 | Brian Bannister | Javier Vazquez | Javier Vazquez | Brian Bannister | | 496 | 585 | -89 |
| 2008-08-13 | @ CHA | 120 | L 0-4 | 54-66 | 5 | 37,838 | Luke Hochevar | Mark Buehrle | Mark Buehrle | Luke Hochevar | | 496 | 589 | -93 |
| 2008-08-14 | @ CHA | 121 | L 2-9 | 54-67 | 5 | 32,788 | Kyle Davies | Lance Broadway | Lance Broadway | Kyle Davies | | 498 | 598 | -100 |
| 2008-08-15 | @ NYA | 122 | W 4-3 | 55-67 | 5 | 53,067 | Gil Meche | Andy Pettitte | Leo Nunez | Mariano Rivera | Joakim Soria | 502 | 601 | -99 |
| 2008-08-16 | @ NYA | 123 | L 2-3 | 55-68 | 5 | 54,180 | Zack Greinke | Sidney Ponson | David Robertson | Jeff Fulchino | | 504 | 604 | -100 |
| 2008-08-17 | @ NYA | 124 | L 6-15 | 55-69 | 5 | 54,114 | Brian Bannister | Mike Mussina | Mike Mussina | Brian Bannister | | 510 | 619 | -109 |
| 2008-08-19 | @ CLE | 125 | L 4-9 | 55-70 | 5 | 18,946 | Luke Hochevar | Anthony Reyes | Anthony Reyes | Luke Hochevar | | 514 | 628 | -114 |
| 2008-08-20 | @ CLE | 126 | L 5-8 | 55-71 | 5 | 23,920 | Gil Meche | Zach Jackson | Juan Rincon | Joakim Soria | Jensen Lewis | 519 | 636 | -117 |
| 2008-08-21 | @ CLE | 127 | L 3-10 | 55-72 | 5 | 21,391 | Zack Greinke | Cliff Lee | Cliff Lee | Zack Greinke | | 522 | 646 | -124 |
| 2008-08-22 | vs DET | 128 | L 3-4 | 55-73 | 5 | 18,361 | Brian Bannister | Justin Verlander | Justin Verlander | Brian Bannister | Fernando Rodney | 525 | 650 | -125 |
| 2008-08-23 | vs DET | 129 | L 0-4 | 55-74 | 5 | 27,346 | Kyle Davies | Zach Miner | Zach Miner | Kyle Davies | | 525 | 654 | -129 |
| 2008-08-24 | vs DET | 130 | W 7-3 | 56-74 | 5 | 16,663 | Brandon Duckworth | Kenny Rogers | Brandon Duckworth | Kenny Rogers | | 532 | 657 | -125 |
| 2008-08-25 | vs TEX | 131 | L 4-9 | 56-75 | 5 | 12,399 | Gil Meche | Scott Feldman | Scott Feldman | Gil Meche | | 536 | 666 | -130 |
| 2008-08-26 | vs TEX | 132 | L 1-2 | 56-76 | 5 | 17,004 | Zack Greinke | Kevin Millwood | Kevin Millwood | Ramon Ramirez | | 537 | 668 | -131 |
| 2008-08-27 | vs TEX | 133 | L 2-3 | 56-77 | 5 | 12,662 | Brian Bannister | Matt Harrison | Matt Harrison | Brian Bannister | Frank Francisco | 539 | 671 | -132 |
| 2008-08-29 | @ DET | 134 | L 3-6 | 56-78 | 5 | 40,206 | Kyle Davies | Zach Miner | Zach Miner | Kyle Davies | | 542 | 677 | -135 |
| 2008-08-30 | @ DET | 135 | W 13-3 | 57-78 | 5 | 40,623 | Brandon Duckworth | Kenny Rogers | Brandon Duckworth | Kenny Rogers | | 555 | 680 | -125 |
| 2008-08-31 | @ DET | 136 | L 2-4 | 57-79 | 5 | 39,782 | Gil Meche | Armando Galarraga | Gary Glover | Kip Wells | Fernando Rodney | 557 | 684 | -127 |
| 2008-09-02 | vs OAK | 137 | W 5-2 | 58-79 | 5 | 11,143 | Zack Greinke | Gio Gonzalez | Zack Greinke | Gio Gonzalez | Joakim Soria | 562 | 686 | -124 |
| 2008-09-04 | vs OAK | 138 | W 5-4 | 60-79 | 5 | 0 | Brian Bannister | Dana Eveland | Joakim Soria | Joey Devine | | 567 | 690 | -123 |
| 2008-09-04 | vs OAK | 139 | W 9-6 | 60-79 | 5 | 12,791 | Kyle Davies | Dan Meyer | Kyle Davies | Dan Meyer | Ramon Ramirez | 576 | 696 | -120 |
| 2008-09-05 | vs CLE | 140 | L 3-9 | 60-80 | 5 | 21,107 | Brandon Duckworth | Anthony Reyes | Edward Mujica | Brandon Duckworth | | 579 | 705 | -126 |
| 2008-09-06 | vs CLE | 141 | W 3-1 | 61-80 | 5 | 18,795 | Gil Meche | Zach Jackson | Gil Meche | Zach Jackson | Joakim Soria | 582 | 706 | -124 |
| 2008-09-07 | vs CLE | 142 | L 1-3 | 61-81 | 5 | 15,023 | Zack Greinke | Cliff Lee | Cliff Lee | Zack Greinke | Jensen Lewis | 583 | 709 | -126 |
| 2008-09-09 | @ MIN | 143 | L 2-7 | 61-82 | 5 | 17,015 | Brian Bannister | Nick Blackburn | Nick Blackburn | Brian Bannister | | 585 | 716 | -131 |
| 2008-09-10 | @ MIN | 144 | L 1-7 | 61-83 | 5 | 20,421 | Kyle Davies | Kevin Slowey | Kevin Slowey | Kyle Davies | | 586 | 723 | -137 |
| 2008-09-11 | @ MIN | 145 | W 3-2 | 62-83 | 5 | 20,138 | Brandon Duckworth | Francisco Liriano | Ramon Ramirez | Matt Guerrier | Joakim Soria | 589 | 725 | -136 |
| 2008-09-12 | @ CLE | 146 | L 5-12 | 62-84 | 5 | 32,843 | Gil Meche | Cliff Lee | Cliff Lee | Gil Meche | | 594 | 737 | -143 |
| 2008-09-13 | @ CLE | 147 | W 8-3 | 64-84 | 5 | 25,783 | Zack Greinke | Fausto Carmona | Zack Greinke | Fausto Carmona | | 602 | 740 | -138 |
| 2008-09-13 | @ CLE | 148 | W 8-4 | 64-84 | 5 | 25,485 | Rob Tejeda | Bryan Bullington | Rob Tejeda | Bryan Bullington | Joakim Soria | 610 | 744 | -134 |
| 2008-09-14 | @ CLE | 149 | W 13-3 | 65-84 | 5 | 29,530 | Brian Bannister | Jeremy Sowers | Brian Bannister | Edward Mujica | | 623 | 747 | -124 |
| 2008-09-15 | vs SEA | 150 | W 3-0 | 66-84 | 5 | 10,307 | Kyle Davies | Carlos Silva | Kyle Davies | Carlos Silva | Joakim Soria | 626 | 747 | -121 |
| 2008-09-16 | vs SEA | 151 | W 6-3 | 67-84 | 5 | 19,135 | Brandon Duckworth | Brandon Morrow | Brandon Duckworth | Brandon Morrow | Joakim Soria | 632 | 750 | -118 |
| 2008-09-17 | vs SEA | 152 | W 5-2 | 68-84 | 5 | 13,382 | Gil Meche | Ryan Rowland-Smith | Gil Meche | Roy Corcoran | Joakim Soria | 637 | 752 | -115 |
| 2008-09-18 | vs SEA | 153 | W 12-0 | 69-84 | 5 | 14,144 | Zack Greinke | Ryan Feierabend | Zack Greinke | Ryan Feierabend | | 649 | 752 | -103 |
| 2008-09-19 | vs CHA | 154 | L 4-9 | 69-85 | 5 | 26,049 | Brian Bannister | Mark Buehrle | Mark Buehrle | Brian Bannister | | 653 | 761 | -108 |
| 2008-09-20 | vs CHA | 155 | W 5-2 | 70-85 | 5 | 23,754 | Kyle Davies | Gavin Floyd | Kyle Davies | Gavin Floyd | Joakim Soria | 658 | 763 | -105 |
| 2008-09-21 | vs CHA | 156 | L 0-3 | 70-86 | 5 | 16,920 | Brandon Duckworth | John Danks | John Danks | Brandon Duckworth | Bobby Jenks | 658 | 766 | -108 |
| 2008-09-22 | @ DET | 157 | W 6-2 | 71-86 | 5 | 36,482 | Gil Meche | Zach Miner | Gil Meche | Zach Miner | | 664 | 768 | -104 |
| 2008-09-23 | @ DET | 158 | W 5-0 | 72-86 | 4 | 35,121 | Zack Greinke | Freddy Garcia | Zack Greinke | Freddy Garcia | | 669 | 768 | -99 |
| 2008-09-24 | @ DET | 159 | W 10-4 | 73-86 | 4 | 35,899 | Brian Bannister | Nate Robertson | Brian Bannister | Nate Robertson | | 679 | 772 | -93 |
| 2008-09-26 | @ MIN | 160 | W 8-1 | 74-86 | 4 | 30,674 | Kyle Davies | Francisco Liriano | Kyle Davies | Francisco Liriano | | 687 | 773 | -86 |
| 2008-09-27 | @ MIN | 161 | W 4-2 | 75-86 | 4 | 38,072 | Gil Meche | Glen Perkins | Gil Meche | Matt Guerrier | Joakim Soria | 691 | 775 | -84 |
| 2008-09-28 | @ MIN | 162 | L 0-6 | 75-87 | 4 | 42,942 | Brandon Duckworth | Scott Baker | Scott Baker | Brandon Duckworth | | 691 | 781 | -90 |