| 2008-03-31 | vs TEX | 1 | W 5-2 | 1-0 | 1 | 46,334 | Erik Bedard | Kevin Millwood | Sean Green | Kevin Millwood | J.J. Putz | 5 | 2 | 3 |
| 2008-04-01 | vs TEX | 2 | L 4-5 | 1-1 | 2 | 25,204 | Felix Hernandez | Vicente Padilla | Joaquin Benoit | J.J. Putz | C.J. Wilson | 9 | 7 | 2 |
| 2008-04-02 | vs TEX | 3 | W 4-1 | 2-1 | 2 | 21,349 | Carlos Silva | Jason Jennings | Carlos Silva | Jason Jennings | Miguel Batista | 13 | 8 | 5 |
| 2008-04-04 | @ BAL | 4 | L 4-7 | 2-2 | 2 | 14,429 | Jarrod Washburn | Steve Trachsel | Steve Trachsel | Jarrod Washburn | George Sherrill | 17 | 15 | 2 |
| 2008-04-05 | @ BAL | 5 | L 4-6 | 2-3 | 3 | 24,824 | Miguel Batista | Adam Loewen | Matt Albers | Miguel Batista | George Sherrill | 21 | 21 | 0 |
| 2008-04-06 | @ BAL | 6 | L 2-3 | 2-4 | 4 | 19,215 | Felix Hernandez | Jeremy Guthrie | Dennis Sarfate | Mark Lowe | | 23 | 24 | -1 |
| 2008-04-07 | @ BAL | 7 | L 4-5 | 2-5 | 4 | 10,774 | Carlos Silva | Daniel Cabrera | Dennis Sarfate | Eric O'Flaherty | George Sherrill | 27 | 29 | -2 |
| 2008-04-08 | @ TBA | 8 | W 6-5 | 3-5 | 4 | 36,048 | Erik Bedard | Matt Garza | Erik Bedard | Gary Glover | Ryan Rowland-Smith | 33 | 34 | -1 |
| 2008-04-09 | @ TBA | 9 | W 7-1 | 4-5 | 3 | 12,106 | Jarrod Washburn | Andy Sonnanstine | Jarrod Washburn | Andy Sonnanstine | | 40 | 35 | 5 |
| 2008-04-10 | @ TBA | 10 | L 0-7 | 4-6 | 4 | 11,898 | Miguel Batista | Edwin Jackson | Edwin Jackson | Miguel Batista | | 40 | 42 | -2 |
| 2008-04-11 | vs ANA | 11 | W 8-5 | 5-6 | 4 | 28,915 | Felix Hernandez | Jered Weaver | Felix Hernandez | Jered Weaver | Mark Lowe | 48 | 47 | 1 |
| 2008-04-12 | vs ANA | 12 | W 8-3 | 6-6 | 3 | 34,963 | Carlos Silva | Jon Garland | Carlos Silva | Jon Garland | | 56 | 50 | 6 |
| 2008-04-13 | vs ANA | 13 | L 5-10 | 6-7 | 3 | 30,664 | Cha-Seung Baek | Joe Saunders | Joe Saunders | Cha-Seung Baek | | 61 | 60 | 1 |
| 2008-04-14 | vs KCA | 14 | L 1-5 | 6-8 | 3 | 16,751 | Jarrod Washburn | Zack Greinke | Zack Greinke | Jarrod Washburn | | 62 | 65 | -3 |
| 2008-04-15 | vs KCA | 15 | W 11-6 | 7-8 | 3 | 17,137 | Miguel Batista | John Bale | Miguel Batista | John Bale | | 73 | 71 | 2 |
| 2008-04-16 | @ OAK | 16 | W 4-2 | 8-8 | 3 | 21,126 | Felix Hernandez | Joe Blanton | Felix Hernandez | Joe Blanton | | 77 | 73 | 4 |
| 2008-04-17 | @ OAK | 17 | W 8-1 | 9-8 | 3 | 10,164 | Carlos Silva | Lenny DiNardo | Carlos Silva | Lenny DiNardo | | 85 | 74 | 11 |
| 2008-04-18 | @ ANA | 18 | L 4-5 | 9-9 | 3 | 43,939 | R.A. Dickey | Joe Saunders | Joe Saunders | R.A. Dickey | Francisco Rodriguez | 89 | 79 | 10 |
| 2008-04-19 | @ ANA | 19 | L 1-4 | 9-10 | 3 | 43,959 | Jarrod Washburn | Ervin Santana | Ervin Santana | Jarrod Washburn | Scot Shields | 90 | 83 | 7 |
| 2008-04-20 | @ ANA | 20 | W 4-2 | 10-10 | 3 | 43,631 | Miguel Batista | Dustin Moseley | Miguel Batista | Dustin Moseley | Ryan Rowland-Smith | 94 | 85 | 9 |
| 2008-04-22 | vs BAL | 21 | W 4-2 | 11-10 | 3 | 17,780 | Felix Hernandez | Jeremy Guthrie | Arthur Rhodes | Jeremy Guthrie | J.J. Putz | 98 | 87 | 11 |
| 2008-04-23 | vs BAL | 22 | L 2-3 | 11-11 | 3 | 16,823 | Carlos Silva | Daniel Cabrera | Daniel Cabrera | Ryan Rowland-Smith | George Sherrill | 100 | 90 | 10 |
| 2008-04-24 | vs BAL | 23 | L 7-8 | 11-12 | 3 | 16,727 | Jarrod Washburn | Adam Loewen | Chad Bradford | Sean Green | George Sherrill | 107 | 98 | 9 |
| 2008-04-25 | vs OAK | 24 | L 3-4 | 11-13 | 3 | 40,845 | Miguel Batista | Dana Eveland | Dana Eveland | Miguel Batista | Huston Street | 110 | 102 | 8 |
| 2008-04-26 | vs OAK | 25 | W 5-3 | 12-13 | 3 | 37,563 | Erik Bedard | Justin Duchscherer | Erik Bedard | Justin Duchscherer | | 115 | 105 | 10 |
| 2008-04-27 | vs OAK | 26 | L 2-4 | 12-14 | 3 | 32,612 | Felix Hernandez | Joe Blanton | Joe Blanton | Felix Hernandez | Huston Street | 117 | 109 | 8 |
| 2008-04-29 | @ CLE | 27 | W 7-2 | 13-14 | 3 | 13,827 | Carlos Silva | Fausto Carmona | Mark Lowe | Rafael Betancourt | | 124 | 111 | 13 |
| 2008-04-30 | @ CLE | 28 | L 3-8 | 13-15 | 3 | 15,279 | Jarrod Washburn | Cliff Lee | Cliff Lee | Jarrod Washburn | | 127 | 119 | 8 |
| 2008-05-01 | @ CLE | 29 | L 2-3 | 13-16 | 3 | 15,722 | Miguel Batista | Paul Byrd | Masahide Kobayashi | Mark Lowe | | 129 | 122 | 7 |
| 2008-05-02 | @ NYA | 30 | L 1-5 | 13-17 | 3 | 52,199 | Erik Bedard | Chien-Ming Wang | Chien-Ming Wang | Erik Bedard | | 130 | 127 | 3 |
| 2008-05-03 | @ NYA | 31 | L 1-6 | 13-18 | 3 | 52,810 | Felix Hernandez | Mike Mussina | Mike Mussina | Felix Hernandez | | 131 | 133 | -2 |
| 2008-05-04 | @ NYA | 32 | L 2-8 | 13-19 | 3 | 53,542 | Carlos Silva | Darrell Rasner | Darrell Rasner | Carlos Silva | | 133 | 141 | -8 |
| 2008-05-05 | vs TEX | 33 | W 7-3 | 14-19 | 3 | 16,637 | Jarrod Washburn | Kevin Millwood | Jarrod Washburn | Kevin Millwood | | 140 | 144 | -4 |
| 2008-05-06 | vs TEX | 34 | L 1-10 | 14-20 | 3 | 15,818 | Miguel Batista | Sidney Ponson | Sidney Ponson | Miguel Batista | | 141 | 154 | -13 |
| 2008-05-07 | vs TEX | 35 | L 0-2 | 14-21 | 4 | 17,173 | Erik Bedard | Vicente Padilla | Vicente Padilla | Erik Bedard | C.J. Wilson | 141 | 156 | -15 |
| 2008-05-08 | vs TEX | 36 | L 0-5 | 14-22 | 4 | 22,922 | Felix Hernandez | Kason Gabbard | Franklyn German | Felix Hernandez | | 141 | 161 | -20 |
| 2008-05-09 | vs CHA | 37 | L 2-4 | 14-23 | 4 | 27,169 | Carlos Silva | Jose Contreras | Jose Contreras | Carlos Silva | Bobby Jenks | 143 | 165 | -22 |
| 2008-05-10 | vs CHA | 38 | L 4-8 | 14-24 | 4 | 33,078 | Jarrod Washburn | Javier Vazquez | Javier Vazquez | Jarrod Washburn | | 147 | 173 | -26 |
| 2008-05-11 | vs CHA | 39 | W 6-3 | 15-24 | 4 | 30,346 | Miguel Batista | Gavin Floyd | Miguel Batista | Gavin Floyd | J.J. Putz | 153 | 176 | -23 |
| 2008-05-12 | @ TEX | 40 | L 12-13 | 15-25 | 4 | 18,509 | Erik Bedard | Vicente Padilla | Doug Mathis | Brandon Morrow | | 165 | 189 | -24 |
| 2008-05-13 | @ TEX | 41 | L 2-5 | 15-26 | 4 | 15,766 | Felix Hernandez | Kason Gabbard | Josh Rupe | Felix Hernandez | Eddie Guardado | 167 | 194 | -27 |
| 2008-05-14 | @ TEX | 42 | W 4-3 | 16-26 | 4 | 22,934 | Carlos Silva | Scott Feldman | J.J. Putz | Franklyn German | Jarrod Washburn | 171 | 197 | -26 |
| 2008-05-16 | vs SDN | 43 | L 4-6 | 16-27 | 4 | 35,586 | Miguel Batista | Chris Young | Chris Young | Miguel Batista | Trevor Hoffman | 175 | 203 | -28 |
| 2008-05-17 | vs SDN | 44 | W 4-2 | 17-27 | 4 | 32,290 | Erik Bedard | Randy Wolf | Erik Bedard | Randy Wolf | J.J. Putz | 179 | 205 | -26 |
| 2008-05-18 | vs SDN | 45 | W 3-2 | 18-27 | 4 | 35,483 | Felix Hernandez | Shawn Estes | Arthur Rhodes | Heath Bell | J.J. Putz | 182 | 207 | -25 |
| 2008-05-20 | @ DET | 46 | L 8-12 | 18-28 | 4 | 39,463 | Carlos Silva | Justin Verlander | Justin Verlander | Carlos Silva | Todd Jones | 190 | 219 | -29 |
| 2008-05-21 | @ DET | 47 | L 4-9 | 18-29 | 4 | 36,495 | Jarrod Washburn | Kenny Rogers | Kenny Rogers | Jarrod Washburn | | 194 | 228 | -34 |
| 2008-05-22 | @ DET | 48 | L 2-9 | 18-30 | 4 | 40,166 | Miguel Batista | Jeremy Bonderman | Jeremy Bonderman | Miguel Batista | Freddy Dolsi | 196 | 237 | -41 |
| 2008-05-23 | @ NYA | 49 | L 2-13 | 18-31 | 4 | 52,005 | Erik Bedard | Andy Pettitte | Andy Pettitte | Erik Bedard | | 198 | 250 | -52 |
| 2008-05-24 | @ NYA | 50 | L 6-12 | 18-32 | 4 | 53,512 | Carlos Silva | Mike Mussina | Mike Mussina | Carlos Silva | | 204 | 262 | -58 |
| 2008-05-25 | @ NYA | 51 | L 5-6 | 18-33 | 4 | 54,269 | Jarrod Washburn | Chien-Ming Wang | Edwar Ramirez | J.J. Putz | Mariano Rivera | 209 | 268 | -59 |
| 2008-05-26 | vs BOS | 52 | L 3-5 | 18-34 | 4 | 35,818 | Felix Hernandez | Bartolo Colon | Bartolo Colon | Felix Hernandez | | 212 | 273 | -61 |
| 2008-05-27 | vs BOS | 53 | W 4-3 | 19-34 | 4 | 30,758 | Miguel Batista | Daisuke Matsuzaka | J.J. Putz | Mike Timlin | | 216 | 276 | -60 |
| 2008-05-28 | vs BOS | 54 | W 1-0 | 20-34 | 4 | 30,752 | Erik Bedard | Tim Wakefield | Erik Bedard | Tim Wakefield | J.J. Putz | 217 | 276 | -59 |
| 2008-05-30 | vs DET | 55 | L 4-7 | 20-35 | 4 | 34,019 | Carlos Silva | Nate Robertson | Nate Robertson | Carlos Silva | Todd Jones | 221 | 283 | -62 |
| 2008-05-31 | vs DET | 56 | W 5-0 | 21-35 | 4 | 33,441 | Felix Hernandez | Justin Verlander | Felix Hernandez | Justin Verlander | | 226 | 283 | -57 |
| 2008-06-01 | vs DET | 57 | L 5-7 | 21-36 | 4 | 38,610 | Miguel Batista | Jeremy Bonderman | Zach Miner | J.J. Putz | | 231 | 290 | -59 |
| 2008-06-02 | vs ANA | 58 | L 2-4 | 21-37 | 4 | 22,110 | Jarrod Washburn | Ervin Santana | Ervin Santana | Jarrod Washburn | Francisco Rodriguez | 233 | 294 | -61 |
| 2008-06-03 | vs ANA | 59 | L 4-5 | 21-38 | 4 | 23,534 | Erik Bedard | Joe Saunders | Joe Saunders | Erik Bedard | Francisco Rodriguez | 237 | 299 | -62 |
| 2008-06-04 | vs ANA | 60 | L 4-5 | 21-39 | 4 | 32,774 | Carlos Silva | Jered Weaver | Jered Weaver | Carlos Silva | Francisco Rodriguez | 241 | 304 | -63 |
| 2008-06-06 | @ BOS | 61 | W 8-0 | 22-39 | 4 | 37,757 | Felix Hernandez | Bartolo Colon | Felix Hernandez | Bartolo Colon | | 249 | 304 | -55 |
| 2008-06-07 | @ BOS | 62 | L 3-11 | 22-40 | 4 | 37,443 | Miguel Batista | Tim Wakefield | Tim Wakefield | Miguel Batista | | 252 | 315 | -63 |
| 2008-06-08 | @ BOS | 63 | L 1-2 | 22-41 | 4 | 37,198 | Erik Bedard | Justin Masterson | Justin Masterson | Sean Green | Jonathan Papelbon | 253 | 317 | -64 |
| 2008-06-09 | @ TOR | 64 | W 3-2 | 23-41 | 4 | 20,073 | Jarrod Washburn | Jesse Litsch | R.A. Dickey | Jason Frasor | J.J. Putz | 256 | 319 | -63 |
| 2008-06-10 | @ TOR | 65 | L 1-3 | 23-42 | 4 | 36,170 | Carlos Silva | Dustin McGowan | Dustin McGowan | Carlos Silva | | 257 | 322 | -65 |
| 2008-06-11 | @ TOR | 66 | W 2-1 | 24-42 | 4 | 35,702 | Felix Hernandez | Shaun Marcum | Felix Hernandez | B.J. Ryan | Brandon Morrow | 259 | 323 | -64 |
| 2008-06-13 | vs WAS | 67 | L 6-7 | 24-43 | 4 | 35,941 | R.A. Dickey | Shawn Hill | Shawn Hill | R.A. Dickey | Jon Rauch | 265 | 330 | -65 |
| 2008-06-14 | vs WAS | 68 | L 2-5 | 24-44 | 4 | 32,145 | Erik Bedard | Tyler Clippard | Tyler Clippard | Miguel Batista | Jon Rauch | 267 | 335 | -68 |
| 2008-06-15 | vs WAS | 69 | L 2-6 | 24-45 | 4 | 38,548 | Jarrod Washburn | Tim Redding | Jesus Colome | Mark Lowe | | 269 | 341 | -72 |
| 2008-06-16 | vs FLO | 70 | L 1-6 | 24-46 | 4 | 21,609 | Carlos Silva | Andrew Miller | Andrew Miller | Carlos Silva | | 270 | 347 | -77 |
| 2008-06-17 | vs FLO | 71 | W 5-4 | 25-46 | 4 | 20,214 | Felix Hernandez | Scott Olsen | Felix Hernandez | Scott Olsen | Brandon Morrow | 275 | 351 | -76 |
| 2008-06-18 | vs FLO | 72 | L 3-8 | 25-47 | 4 | 24,163 | R.A. Dickey | Ryan Tucker | Ryan Tucker | R.A. Dickey | | 278 | 359 | -81 |
| 2008-06-20 | @ ATL | 73 | W 10-2 | 26-47 | 4 | 40,268 | Erik Bedard | Jorge Campillo | Ryan Rowland-Smith | Jorge Campillo | | 288 | 361 | -73 |
| 2008-06-21 | @ ATL | 74 | L 4-5 | 26-48 | 4 | 47,158 | Jarrod Washburn | Jair Jurrjens | Blaine Boyer | Miguel Batista | | 292 | 366 | -74 |
| 2008-06-22 | @ ATL | 75 | L 3-8 | 26-49 | 4 | 30,965 | Carlos Silva | Tim Hudson | Tim Hudson | Carlos Silva | | 295 | 374 | -79 |
| 2008-06-23 | @ NYN | 76 | W 5-2 | 27-49 | 4 | 49,789 | Felix Hernandez | Johan Santana | Ryan Rowland-Smith | Johan Santana | Arthur Rhodes | 300 | 376 | -76 |
| 2008-06-24 | @ NYN | 77 | W 11-0 | 28-49 | 4 | 49,386 | R.A. Dickey | Oliver Perez | R.A. Dickey | Oliver Perez | | 311 | 376 | -65 |
| 2008-06-25 | @ NYN | 78 | L 2-8 | 28-50 | 4 | 52,154 | Miguel Batista | John Maine | John Maine | Miguel Batista | | 313 | 384 | -71 |
| 2008-06-27 | @ SDN | 79 | W 5-2 | 29-50 | 4 | 28,640 | Jarrod Washburn | Randy Wolf | Jarrod Washburn | Randy Wolf | Brandon Morrow | 318 | 386 | -68 |
| 2008-06-28 | @ SDN | 80 | W 4-2 | 30-50 | 4 | 36,396 | Carlos Silva | Cha-Seung Baek | Carlos Silva | Cha-Seung Baek | Brandon Morrow | 322 | 388 | -66 |
| 2008-06-29 | @ SDN | 81 | W 9-2 | 31-50 | 4 | 29,966 | Erik Bedard | Jake Peavy | Erik Bedard | Jake Peavy | | 331 | 390 | -59 |
| 2008-06-30 | vs TOR | 82 | L 0-2 | 31-51 | 4 | 30,179 | R.A. Dickey | Roy Halladay | Roy Halladay | R.A. Dickey | | 331 | 392 | -61 |
| 2008-07-01 | vs TOR | 83 | W 7-6 | 32-51 | 4 | 24,586 | Ryan Rowland-Smith | Jesse Litsch | Brandon Morrow | Scott Downs | | 338 | 398 | -60 |
| 2008-07-02 | vs TOR | 84 | W 4-2 | 33-51 | 4 | 23,283 | Jarrod Washburn | Dustin McGowan | Jarrod Washburn | Dustin McGowan | Brandon Morrow | 342 | 400 | -58 |
| 2008-07-03 | vs DET | 85 | L 4-8 | 33-52 | 4 | 22,523 | Carlos Silva | Justin Verlander | Justin Verlander | Carlos Silva | Fernando Rodney | 346 | 408 | -62 |
| 2008-07-04 | vs DET | 86 | W 4-1 | 34-52 | 4 | 30,564 | Erik Bedard | Kenny Rogers | Erik Bedard | Kenny Rogers | Brandon Morrow | 350 | 409 | -59 |
| 2008-07-05 | vs DET | 87 | W 3-2 | 35-52 | 4 | 30,373 | R.A. Dickey | Armando Galarraga | Miguel Batista | Fernando Rodney | Brandon Morrow | 353 | 411 | -58 |
| 2008-07-06 | vs DET | 88 | L 1-2 | 35-53 | 4 | 29,083 | Ryan Rowland-Smith | Nate Robertson | Aquilino Lopez | Jamie Burke | Todd Jones | 354 | 413 | -59 |
| 2008-07-07 | @ OAK | 89 | L 3-4 | 35-54 | 4 | 11,129 | Jarrod Washburn | Dana Eveland | Dana Eveland | Jarrod Washburn | Huston Street | 357 | 417 | -60 |
| 2008-07-08 | @ OAK | 90 | L 0-2 | 35-55 | 4 | 12,543 | Carlos Silva | Justin Duchscherer | Justin Duchscherer | Carlos Silva | | 357 | 419 | -62 |
| 2008-07-09 | @ OAK | 91 | W 6-4 | 36-55 | 4 | 21,128 | Miguel Batista | Joe Blanton | Roy Corcoran | Joe Blanton | Brandon Morrow | 363 | 423 | -60 |
| 2008-07-10 | @ OAK | 92 | L 2-3 | 36-56 | 4 | 15,187 | R.A. Dickey | Greg Smith | Huston Street | Cesar Jimenez | | 365 | 426 | -61 |
| 2008-07-11 | @ KCA | 93 | L 1-3 | 36-57 | 4 | 25,345 | Felix Hernandez | Luke Hochevar | Luke Hochevar | Felix Hernandez | Joakim Soria | 366 | 429 | -63 |
| 2008-07-12 | @ KCA | 94 | L 4-5 | 36-58 | 4 | 23,792 | Jarrod Washburn | Gil Meche | Horacio Ramirez | Brandon Morrow | | 370 | 434 | -64 |
| 2008-07-13 | @ KCA | 95 | W 4-3 | 37-58 | 4 | 21,421 | Carlos Silva | Kyle Davies | Sean Green | Joakim Soria | Brandon Morrow | 374 | 437 | -63 |
| 2008-07-18 | vs CLE | 96 | W 8-2 | 38-58 | 4 | 42,570 | Felix Hernandez | Aaron Laffey | Felix Hernandez | Aaron Laffey | | 382 | 439 | -57 |
| 2008-07-19 | vs CLE | 97 | L 6-9 | 38-59 | 4 | 37,869 | Miguel Batista | Jeremy Sowers | Jeremy Sowers | Miguel Batista | | 388 | 448 | -60 |
| 2008-07-20 | vs CLE | 98 | L 2-6 | 38-60 | 4 | 32,230 | Carlos Silva | Cliff Lee | Cliff Lee | Carlos Silva | | 390 | 454 | -64 |
| 2008-07-21 | vs BOS | 99 | L 0-4 | 38-61 | 4 | 37,861 | Jarrod Washburn | Jon Lester | Jon Lester | Jarrod Washburn | Jonathan Papelbon | 390 | 458 | -68 |
| 2008-07-22 | vs BOS | 100 | L 2-4 | 38-62 | 4 | 38,425 | R.A. Dickey | Daisuke Matsuzaka | Daisuke Matsuzaka | R.A. Dickey | Jonathan Papelbon | 392 | 462 | -70 |
| 2008-07-23 | vs BOS | 101 | L 3-6 | 38-63 | 4 | 43,231 | Felix Hernandez | Clay Buchholz | Jonathan Papelbon | Sean Green | Craig Hansen | 395 | 468 | -73 |
| 2008-07-25 | @ TOR | 102 | L 4-5 | 38-64 | 4 | 28,463 | Miguel Batista | John Parrish | Jesse Carlson | Mark Lowe | | 399 | 473 | -74 |
| 2008-07-26 | @ TOR | 103 | L 3-8 | 38-65 | 4 | 33,041 | R.A. Dickey | David Purcey | David Purcey | R.A. Dickey | | 402 | 481 | -79 |
| 2008-07-27 | @ TOR | 104 | W 5-1 | 39-65 | 4 | 33,367 | Jarrod Washburn | Shaun Marcum | Jarrod Washburn | Shaun Marcum | | 407 | 482 | -75 |
| 2008-07-28 | @ TEX | 105 | W 7-5 | 40-65 | 4 | 21,742 | Felix Hernandez | Scott Feldman | Sean Green | Frank Francisco | Brandon Morrow | 414 | 487 | -73 |
| 2008-07-29 | @ TEX | 106 | L 10-11 | 40-66 | 4 | 17,618 | Carlos Silva | Luis Mendoza | C.J. Wilson | J.J. Putz | | 424 | 498 | -74 |
| 2008-07-30 | @ TEX | 107 | L 3-4 | 40-67 | 4 | 23,894 | Miguel Batista | Vicente Padilla | Eddie Guardado | Arthur Rhodes | C.J. Wilson | 427 | 502 | -75 |
| 2008-07-31 | @ TEX | 108 | W 8-5 | 41-67 | 4 | 17,839 | R.A. Dickey | Matt Harrison | R.A. Dickey | Matt Harrison | | 435 | 507 | -72 |
| 2008-08-01 | vs BAL | 109 | L 5-10 | 41-68 | 4 | 28,114 | Jarrod Washburn | Garrett Olson | Garrett Olson | Jarrod Washburn | | 440 | 517 | -77 |
| 2008-08-02 | vs BAL | 110 | L 1-3 | 41-69 | 4 | 30,502 | Felix Hernandez | Jeremy Guthrie | Jeremy Guthrie | Felix Hernandez | | 441 | 520 | -79 |
| 2008-08-03 | vs BAL | 111 | W 8-4 | 42-69 | 4 | 33,334 | Carlos Silva | Daniel Cabrera | J.J. Putz | Daniel Cabrera | | 449 | 524 | -75 |
| 2008-08-04 | vs MIN | 112 | W 11-6 | 43-69 | 4 | 27,758 | Miguel Batista | Glen Perkins | Roy Corcoran | Brian Bass | | 460 | 530 | -70 |
| 2008-08-05 | vs MIN | 113 | W 8-7 | 44-69 | 4 | 26,083 | R.A. Dickey | Scott Baker | J.J. Putz | Matt Guerrier | | 468 | 537 | -69 |
| 2008-08-06 | vs MIN | 114 | L 3-7 | 44-70 | 4 | 30,441 | Jarrod Washburn | Nick Blackburn | Nick Blackburn | Jarrod Washburn | | 471 | 544 | -73 |
| 2008-08-07 | vs TBA | 115 | W 2-1 | 45-70 | 4 | 25,423 | Felix Hernandez | Andy Sonnanstine | J.J. Putz | Dan Wheeler | | 473 | 545 | -72 |
| 2008-08-08 | vs TBA | 116 | L 3-5 | 45-71 | 4 | 30,220 | Carlos Silva | James Shields | James Shields | Carlos Silva | Troy Percival | 476 | 550 | -74 |
| 2008-08-09 | vs TBA | 117 | L 7-8 | 45-72 | 4 | 27,905 | Ryan Rowland-Smith | Matt Garza | Chad Bradford | Miguel Batista | Troy Percival | 483 | 558 | -75 |
| 2008-08-10 | vs TBA | 118 | L 3-11 | 45-73 | 4 | 30,336 | R.A. Dickey | Edwin Jackson | Edwin Jackson | R.A. Dickey | | 486 | 569 | -83 |
| 2008-08-12 | @ ANA | 119 | L 3-7 | 45-74 | 4 | 42,086 | Jarrod Washburn | Jon Garland | Jon Garland | Jarrod Washburn | Francisco Rodriguez | 489 | 576 | -87 |
| 2008-08-13 | @ ANA | 120 | W 10-7 | 46-74 | 4 | 42,754 | Felix Hernandez | Ervin Santana | Roy Corcoran | Justin Speier | | 499 | 583 | -84 |
| 2008-08-15 | @ MIN | 121 | L 3-9 | 46-75 | 4 | 32,208 | Carlos Silva | Francisco Liriano | Francisco Liriano | Carlos Silva | | 502 | 592 | -90 |
| 2008-08-16 | @ MIN | 122 | L 6-7 | 46-76 | 4 | 36,316 | Ryan Rowland-Smith | Scott Baker | Dennys Reyes | Cesar Jimenez | | 508 | 599 | -91 |
| 2008-08-17 | @ MIN | 123 | L 8-11 | 46-77 | 4 | 35,478 | Ryan Feierabend | Glen Perkins | Glen Perkins | Ryan Feierabend | Joe Nathan | 516 | 610 | -94 |
| 2008-08-18 | @ CHA | 124 | L 5-13 | 46-78 | 4 | 39,002 | Jarrod Washburn | Mark Buehrle | Mark Buehrle | Jarrod Washburn | | 521 | 623 | -102 |
| 2008-08-19 | @ CHA | 125 | L 0-5 | 46-79 | 4 | 26,414 | Felix Hernandez | Clayton Richard | Clayton Richard | Felix Hernandez | | 521 | 628 | -107 |
| 2008-08-20 | @ CHA | 126 | L 3-15 | 46-80 | 4 | 27,000 | R.A. Dickey | Gavin Floyd | Gavin Floyd | R.A. Dickey | | 524 | 643 | -119 |
| 2008-08-21 | vs OAK | 127 | L 0-2 | 46-81 | 4 | 25,611 | Ryan Rowland-Smith | Greg Smith | Greg Smith | Ryan Rowland-Smith | Brad Ziegler | 524 | 645 | -121 |
| 2008-08-22 | vs OAK | 128 | W 7-5 | 47-81 | 4 | 26,603 | Ryan Feierabend | Gio Gonzalez | Roy Corcoran | Jerry Blevins | J.J. Putz | 531 | 650 | -119 |
| 2008-08-23 | vs OAK | 129 | L 1-5 | 47-82 | 4 | 34,145 | Jarrod Washburn | Dana Eveland | Dana Eveland | Jarrod Washburn | | 532 | 655 | -123 |
| 2008-08-24 | vs OAK | 130 | W 8-4 | 48-82 | 4 | 28,731 | Felix Hernandez | Dan Meyer | Felix Hernandez | Dan Meyer | J.J. Putz | 540 | 659 | -119 |
| 2008-08-25 | vs MIN | 131 | W 4-2 | 49-82 | 4 | 23,277 | Miguel Batista | Francisco Liriano | R.A. Dickey | Jesse Crain | | 544 | 661 | -117 |
| 2008-08-26 | vs MIN | 132 | W 3-2 | 50-82 | 4 | 26,292 | Ryan Rowland-Smith | Scott Baker | Ryan Rowland-Smith | Scott Baker | Roy Corcoran | 547 | 663 | -116 |
| 2008-08-27 | vs MIN | 133 | L 5-6 | 50-83 | 4 | 23,581 | Ryan Feierabend | Glen Perkins | Glen Perkins | Sean Green | Joe Nathan | 552 | 669 | -117 |
| 2008-08-29 | @ CLE | 134 | W 3-2 | 51-83 | 4 | 26,047 | Felix Hernandez | Jeremy Sowers | Felix Hernandez | Jeremy Sowers | J.J. Putz | 555 | 671 | -116 |
| 2008-08-30 | @ CLE | 135 | W 4-3 | 52-83 | 4 | 33,387 | Jarrod Washburn | Anthony Reyes | J.J. Putz | Jensen Lewis | Randy Messenger | 559 | 674 | -115 |
| 2008-08-31 | @ CLE | 136 | W 6-4 | 53-83 | 4 | 35,376 | Ryan Rowland-Smith | Zach Jackson | Ryan Rowland-Smith | Zach Jackson | Roy Corcoran | 565 | 678 | -113 |
| 2008-09-01 | @ TEX | 137 | W 12-6 | 54-83 | 4 | 16,171 | Carlos Silva | Matt Harrison | Sean Green | Luis Mendoza | | 577 | 684 | -107 |
| 2008-09-02 | @ TEX | 138 | L 4-6 | 54-84 | 4 | 14,521 | Ryan Feierabend | Brandon McCarthy | Brandon McCarthy | Ryan Feierabend | Frank Francisco | 581 | 690 | -109 |
| 2008-09-03 | @ TEX | 139 | L 0-1 | 54-85 | 4 | 12,882 | Felix Hernandez | Dustin Nippert | Dustin Nippert | Felix Hernandez | Frank Francisco | 581 | 691 | -110 |
| 2008-09-05 | vs NYA | 140 | W 3-1 | 55-85 | 4 | 39,518 | Brandon Morrow | Andy Pettitte | Brandon Morrow | Andy Pettitte | J.J. Putz | 584 | 692 | -108 |
| 2008-09-06 | vs NYA | 141 | L 4-7 | 55-86 | 4 | 44,473 | Ryan Rowland-Smith | Sidney Ponson | Sidney Ponson | Sean Green | Mariano Rivera | 588 | 699 | -111 |
| 2008-09-07 | vs NYA | 142 | W 5-2 | 56-86 | 4 | 42,677 | Ryan Feierabend | Mike Mussina | Ryan Feierabend | Mike Mussina | J.J. Putz | 593 | 701 | -108 |
| 2008-09-09 | vs TEX | 143 | L 3-7 | 56-87 | 4 | 22,704 | Felix Hernandez | Vicente Padilla | Vicente Padilla | Felix Hernandez | Warner Madrigal | 596 | 708 | -112 |
| 2008-09-10 | vs TEX | 144 | W 8-7 | 57-87 | 4 | 23,644 | Cesar Jimenez | Kevin Millwood | Roy Corcoran | Kevin Millwood | J.J. Putz | 604 | 715 | -111 |
| 2008-09-11 | @ ANA | 145 | L 4-7 | 57-88 | 4 | 38,205 | Brandon Morrow | Jered Weaver | Jered Weaver | Brandon Morrow | Francisco Rodriguez | 608 | 722 | -114 |
| 2008-09-12 | @ ANA | 146 | L 3-5 | 57-89 | 4 | 43,743 | Ryan Rowland-Smith | Joe Saunders | Jose Arredondo | Miguel Batista | | 611 | 727 | -116 |
| 2008-09-13 | @ ANA | 147 | L 2-5 | 57-90 | 4 | 43,757 | Ryan Feierabend | Jon Garland | Jon Garland | Ryan Feierabend | Francisco Rodriguez | 613 | 732 | -119 |
| 2008-09-14 | @ ANA | 148 | L 3-4 | 57-91 | 4 | 41,528 | Felix Hernandez | Ervin Santana | Jose Arredondo | Roy Corcoran | | 616 | 736 | -120 |
| 2008-09-15 | @ KCA | 149 | L 0-3 | 57-92 | 4 | 10,307 | Carlos Silva | Kyle Davies | Kyle Davies | Carlos Silva | Joakim Soria | 616 | 739 | -123 |
| 2008-09-16 | @ KCA | 150 | L 3-6 | 57-93 | 4 | 19,135 | Brandon Morrow | Brandon Duckworth | Brandon Duckworth | Brandon Morrow | Joakim Soria | 619 | 745 | -126 |
| 2008-09-17 | @ KCA | 151 | L 2-5 | 57-94 | 4 | 13,382 | Ryan Rowland-Smith | Gil Meche | Gil Meche | Roy Corcoran | Joakim Soria | 621 | 750 | -129 |
| 2008-09-18 | @ KCA | 152 | L 0-12 | 57-95 | 4 | 14,144 | Ryan Feierabend | Zack Greinke | Zack Greinke | Ryan Feierabend | | 621 | 762 | -141 |
| 2008-09-19 | @ OAK | 153 | L 0-2 | 57-96 | 4 | 30,149 | Felix Hernandez | Dana Eveland | Dana Eveland | Felix Hernandez | Brad Ziegler | 621 | 764 | -143 |
| 2008-09-20 | @ OAK | 154 | L 7-8 | 57-97 | 4 | 18,756 | Carlos Silva | Kirk Saarloos | Huston Street | Justin Thomas | Brad Ziegler | 628 | 772 | -144 |
| 2008-09-21 | @ OAK | 155 | L 3-5 | 57-98 | 4 | 18,707 | Brandon Morrow | Sean Gallagher | Brad Ziegler | Miguel Batista | Joey Devine | 631 | 777 | -146 |
| 2008-09-22 | vs ANA | 156 | L 1-2 | 57-99 | 4 | 19,717 | Ryan Rowland-Smith | Ervin Santana | Ervin Santana | Ryan Rowland-Smith | Francisco Rodriguez | 632 | 779 | -147 |
| 2008-09-23 | vs ANA | 157 | W 9-6 | 58-99 | 4 | 19,065 | Ryan Feierabend | Jered Weaver | Roy Corcoran | Kevin Jepsen | J.J. Putz | 641 | 785 | -144 |
| 2008-09-24 | vs ANA | 158 | L 5-6 | 58-100 | 4 | 19,015 | Felix Hernandez | Jon Garland | Darren Oliver | Mark Lowe | Francisco Rodriguez | 646 | 791 | -145 |
| 2008-09-25 | vs ANA | 159 | L 4-6 | 58-101 | 4 | 16,939 | Cesar Jimenez | Dustin Moseley | Jose Arredondo | J.J. Putz | Scot Shields | 650 | 797 | -147 |
| 2008-09-26 | vs OAK | 160 | W 10-8 | 59-101 | 4 | 24,662 | Brandon Morrow | Sean Gallagher | Brandon Morrow | Sean Gallagher | Roy Corcoran | 660 | 805 | -145 |
| 2008-09-27 | vs OAK | 161 | W 7-3 | 60-101 | 4 | 24,440 | Ryan Rowland-Smith | Greg Smith | Ryan Rowland-Smith | Greg Smith | Sean Green | 667 | 808 | -141 |
| 2008-09-28 | vs OAK | 162 | W 4-3 | 61-101 | 4 | 27,110 | R.A. Dickey | Josh Outman | R.A. Dickey | Josh Outman | J.J. Putz | 671 | 811 | -140 |