| 2008-03-31 | @ SDN | 1 | L 0-4 | - | | 44,965 | Roy Oswalt | Jake Peavy | Jake Peavy | Roy Oswalt | | 0 | 4 | -4 |
| 2008-04-01 | @ SDN | 2 | L 1-2 | - | | 20,825 | Brandon Backe | Chris Young | Chris Young | Brandon Backe | Trevor Hoffman | 1 | 6 | -5 |
| 2008-04-02 | @ SDN | 3 | W 9-6 | - | | 18,714 | Wandy Rodriguez | Greg Maddux | Jose Valverde | Trevor Hoffman | | 10 | 12 | -2 |
| 2008-04-03 | @ SDN | 4 | L 2-3 | - | | 24,432 | Shawn Chacon | Randy Wolf | Enrique Gonzalez | Oscar Villarreal | Trevor Hoffman | 12 | 15 | -3 |
| 2008-04-04 | @ CHN | 5 | W 4-3 | - | | 37,812 | Chris Sampson | Rich Hill | Wesley Wright | Jon Lieber | Jose Valverde | 16 | 18 | -2 |
| 2008-04-05 | @ CHN | 6 | L 7-9 | - | | 40,707 | Roy Oswalt | Jason Marquis | Kevin Hart | Roy Oswalt | Kerry Wood | 23 | 27 | -4 |
| 2008-04-06 | @ CHN | 7 | L 2-3 | - | | 40,929 | Brandon Backe | Carlos Zambrano | Carlos Zambrano | Oscar Villarreal | Kerry Wood | 25 | 30 | -5 |
| 2008-04-07 | vs SLN | 8 | W 5-3 | - | | 43,483 | Wandy Rodriguez | Todd Wellemeyer | Jose Valverde | Kyle McClellan | | 30 | 33 | -3 |
| 2008-04-08 | vs SLN | 9 | L 3-5 | - | | 30,184 | Shawn Chacon | Brad Thompson | Anthony Reyes | Geoff Geary | Jason Isringhausen | 33 | 38 | -5 |
| 2008-04-09 | vs SLN | 10 | L 4-6 | - | | 29,187 | Chris Sampson | Braden Looper | Braden Looper | Chris Sampson | Jason Isringhausen | 37 | 44 | -7 |
| 2008-04-11 | vs FLO | 11 | L 6-10 | - | | 34,191 | Roy Oswalt | Ricky Nolasco | Ricky Nolasco | Roy Oswalt | | 43 | 54 | -11 |
| 2008-04-12 | vs FLO | 12 | W 5-0 | - | | 34,336 | Brandon Backe | Andrew Miller | Brandon Backe | Andrew Miller | | 48 | 54 | -6 |
| 2008-04-13 | vs FLO | 13 | W 5-1 | - | | 29,766 | Wandy Rodriguez | Burke Badenhop | Wandy Rodriguez | Burke Badenhop | | 53 | 55 | -2 |
| 2008-04-15 | @ PHI | 14 | L 3-4 | - | | 34,609 | Shawn Chacon | Adam Eaton | Rudy Seanez | Jose Valverde | | 56 | 59 | -3 |
| 2008-04-16 | @ PHI | 15 | W 2-1 | - | | 31,644 | Roy Oswalt | Kyle Kendrick | Roy Oswalt | Kyle Kendrick | Doug Brocail | 58 | 60 | -2 |
| 2008-04-17 | @ PHI | 16 | L 2-10 | - | | 33,526 | Brandon Backe | Brett Myers | Brett Myers | Brandon Backe | | 60 | 70 | -10 |
| 2008-04-18 | vs COL | 17 | L 5-11 | - | | 34,272 | Chris Sampson | Franklin Morales | Franklin Morales | Chris Sampson | | 65 | 81 | -16 |
| 2008-04-19 | vs COL | 18 | L 2-3 | - | | 34,540 | Wandy Rodriguez | Aaron Cook | Aaron Cook | Oscar Villarreal | Manuel Corpas | 67 | 84 | -17 |
| 2008-04-20 | vs COL | 19 | W 6-4 | - | | 35,286 | Shawn Chacon | Ubaldo Jimenez | Wesley Wright | Brian Fuentes | Jose Valverde | 73 | 88 | -15 |
| 2008-04-21 | vs SDN | 20 | W 10-3 | - | | 28,600 | Roy Oswalt | Justin Germano | Roy Oswalt | Justin Germano | | 83 | 91 | -8 |
| 2008-04-22 | vs SDN | 21 | W 11-7 | - | | 33,434 | Brandon Backe | Jake Peavy | Jose Valverde | Heath Bell | | 94 | 98 | -4 |
| 2008-04-23 | @ CIN | 22 | W 9-3 | - | | 16,017 | Chris Sampson | Bronson Arroyo | Chris Sampson | Bronson Arroyo | | 103 | 101 | 2 |
| 2008-04-24 | @ CIN | 23 | W 5-3 | - | | 17,403 | Jack Cassel | Johnny Cueto | Jack Cassel | Johnny Cueto | Jose Valverde | 108 | 104 | 4 |
| 2008-04-25 | @ SLN | 24 | W 3-2 | - | | 41,193 | Shawn Chacon | Braden Looper | Wesley Wright | Jason Isringhausen | Jose Valverde | 111 | 106 | 5 |
| 2008-04-26 | @ SLN | 25 | L 3-4 | - | | 43,040 | Roy Oswalt | Adam Wainwright | Adam Wainwright | Dave Borkowski | | 114 | 110 | 4 |
| 2008-04-27 | @ SLN | 26 | L 1-5 | - | | 44,222 | Brandon Backe | Kyle Lohse | Kyle Lohse | Brandon Backe | Kyle McClellan | 115 | 115 | 0 |
| 2008-04-28 | @ ARI | 27 | L 3-5 | - | | 19,868 | Chris Sampson | Dan Haren | Dan Haren | Chris Sampson | Brandon Lyon | 118 | 120 | -2 |
| 2008-04-29 | @ ARI | 28 | W 6-4 | - | | 20,241 | Jack Cassel | Edgar Gonzalez | Doug Brocail | Edgar Gonzalez | Jose Valverde | 124 | 124 | 0 |
| 2008-04-30 | @ ARI | 29 | L 7-8 | - | | 21,519 | Shawn Chacon | Randy Johnson | Brandon Medders | Dave Borkowski | Brandon Lyon | 131 | 132 | -1 |
| 2008-05-02 | vs MIL | 30 | W 7-4 | - | | 39,715 | Roy Oswalt | Carlos Villanueva | Roy Oswalt | Carlos Villanueva | Jose Valverde | 138 | 136 | 2 |
| 2008-05-03 | vs MIL | 31 | W 6-2 | - | | 35,002 | Brandon Backe | Manny Parra | Brandon Backe | Manny Parra | | 144 | 138 | 6 |
| 2008-05-04 | vs MIL | 32 | W 8-6 | - | | 38,301 | Chris Sampson | Ben Sheets | Tim Byrdak | Mitch Stetter | | 152 | 144 | 8 |
| 2008-05-06 | vs WAS | 33 | W 6-5 | - | | 30,335 | Shawn Chacon | Shawn Hill | Doug Brocail | Luis Ayala | Jose Valverde | 158 | 149 | 9 |
| 2008-05-07 | vs WAS | 34 | W 4-3 | - | | 30,432 | Roy Oswalt | Odalis Perez | Jose Valverde | Joel Hanrahan | | 162 | 152 | 10 |
| 2008-05-08 | vs WAS | 35 | L 3-8 | - | | 33,433 | Brandon Backe | John Lannan | John Lannan | Brandon Backe | | 165 | 160 | 5 |
| 2008-05-09 | @ LAN | 36 | W 7-1 | - | | 52,658 | Brian Moehler | Derek Lowe | Brian Moehler | Derek Lowe | | 172 | 161 | 11 |
| 2008-05-10 | @ LAN | 37 | W 5-0 | - | | 45,212 | Chris Sampson | Chad Billingsley | Chris Sampson | Chad Billingsley | | 177 | 161 | 16 |
| 2008-05-11 | @ LAN | 38 | W 8-5 | - | | 40,217 | Shawn Chacon | Hiroki Kuroda | Geoff Geary | Jonathan Broxton | Jose Valverde | 185 | 166 | 19 |
| 2008-05-12 | @ SFN | 39 | W 7-3 | - | | 30,165 | Roy Oswalt | Barry Zito | Roy Oswalt | Vinnie Chulk | Jose Valverde | 192 | 169 | 23 |
| 2008-05-13 | @ SFN | 40 | L 2-4 | - | | 30,858 | Brandon Backe | Matt Cain | Matt Cain | Brandon Backe | Brian Wilson | 194 | 173 | 21 |
| 2008-05-14 | @ SFN | 41 | W 6-3 | - | | 33,070 | Brian Moehler | Pat Misch | Oscar Villarreal | Jack Taschner | Jose Valverde | 200 | 176 | 24 |
| 2008-05-15 | @ SFN | 42 | W 8-7 | - | | 33,771 | Chris Sampson | Tim Lincecum | Tim Byrdak | Vinnie Chulk | Jose Valverde | 208 | 183 | 25 |
| 2008-05-16 | @ TEX | 43 | L 8-16 | - | | 32,117 | Shawn Chacon | Sidney Ponson | Jamey Wright | Wesley Wright | | 216 | 199 | 17 |
| 2008-05-17 | @ TEX | 44 | L 2-6 | - | | 38,534 | Roy Oswalt | Vicente Padilla | Vicente Padilla | Roy Oswalt | | 218 | 205 | 13 |
| 2008-05-18 | @ TEX | 45 | W 5-4 | - | | 33,561 | Brandon Backe | Kason Gabbard | Brandon Backe | Kason Gabbard | Jose Valverde | 223 | 209 | 14 |
| 2008-05-19 | vs CHN | 46 | L 2-7 | - | | 32,458 | Brian Moehler | Ted Lilly | Ted Lilly | Brian Moehler | | 225 | 216 | 9 |
| 2008-05-20 | vs CHN | 47 | W 4-2 | - | | 33,339 | Chris Sampson | Ryan Dempster | Chris Sampson | Ryan Dempster | Jose Valverde | 229 | 218 | 11 |
| 2008-05-21 | vs CHN | 48 | W 5-3 | - | | 33,251 | Shawn Chacon | Sean Gallagher | Shawn Chacon | Sean Gallagher | Jose Valverde | 234 | 221 | 13 |
| 2008-05-22 | vs PHI | 49 | L 5-7 | - | | 29,263 | Roy Oswalt | Kyle Kendrick | Chad Durbin | Wesley Wright | Brad Lidge | 239 | 228 | 11 |
| 2008-05-23 | vs PHI | 50 | W 4-3 | - | | 41,152 | Brandon Backe | Adam Eaton | Brandon Backe | Adam Eaton | Jose Valverde | 243 | 231 | 12 |
| 2008-05-24 | vs PHI | 51 | W 4-3 | - | | 42,660 | Brian Moehler | Brett Myers | Brian Moehler | Brett Myers | Doug Brocail | 247 | 234 | 13 |
| 2008-05-25 | vs PHI | 52 | L 6-15 | - | | 43,079 | Chris Sampson | Cole Hamels | Rudy Seanez | Fernando Nieve | | 253 | 249 | 4 |
| 2008-05-27 | @ SLN | 53 | W 8-2 | - | | 41,104 | Shawn Chacon | Braden Looper | Shawn Chacon | Braden Looper | | 261 | 251 | 10 |
| 2008-05-28 | @ SLN | 54 | L 1-6 | - | | 41,115 | Wandy Rodriguez | Adam Wainwright | Adam Wainwright | Wandy Rodriguez | | 262 | 257 | 5 |
| 2008-05-29 | @ SLN | 55 | L 2-3 | - | | 41,786 | Roy Oswalt | Kyle Lohse | Kyle Lohse | Roy Oswalt | Ryan Franklin | 264 | 260 | 4 |
| 2008-05-30 | @ MIL | 56 | L 1-5 | - | | 32,039 | Brandon Backe | Manny Parra | Manny Parra | Brandon Backe | | 265 | 265 | 0 |
| 2008-05-31 | @ MIL | 57 | L 1-4 | - | | 42,913 | Brian Moehler | Ben Sheets | Ben Sheets | Brian Moehler | Salomon Torres | 266 | 269 | -3 |
| 2008-06-01 | @ MIL | 58 | L 1-10 | - | | 44,613 | Shawn Chacon | David Bush | David Bush | Shawn Chacon | | 267 | 279 | -12 |
| 2008-06-03 | @ PIT | 59 | W 2-0 | - | | 13,183 | Wandy Rodriguez | Phil Dumatrait | Wandy Rodriguez | Phil Dumatrait | Jose Valverde | 269 | 279 | -10 |
| 2008-06-04 | @ PIT | 60 | L 2-5 | - | | 9,392 | Roy Oswalt | Zach Duke | Zach Duke | Roy Oswalt | Matt Capps | 271 | 284 | -13 |
| 2008-06-05 | @ PIT | 61 | L 3-4 | - | | 10,728 | Brandon Backe | Paul Maholm | Paul Maholm | Brandon Backe | Matt Capps | 274 | 288 | -14 |
| 2008-06-06 | vs SLN | 62 | W 6-1 | - | | 38,596 | Brian Moehler | Braden Looper | Brian Moehler | Braden Looper | | 280 | 289 | -9 |
| 2008-06-07 | vs SLN | 63 | L 4-8 | - | | 39,811 | Shawn Chacon | Adam Wainwright | Adam Wainwright | Shawn Chacon | | 284 | 297 | -13 |
| 2008-06-08 | vs SLN | 64 | L 4-5 | - | | 39,923 | Wandy Rodriguez | Kyle Lohse | Kyle Lohse | Wandy Rodriguez | Ryan Franklin | 288 | 302 | -14 |
| 2008-06-10 | vs MIL | 65 | W 6-1 | - | | 35,058 | Roy Oswalt | Seth McClung | Roy Oswalt | Seth McClung | | 294 | 303 | -9 |
| 2008-06-11 | vs MIL | 66 | L 6-10 | - | | 33,806 | Brandon Backe | Manny Parra | Manny Parra | Brandon Backe | | 300 | 313 | -13 |
| 2008-06-12 | vs MIL | 67 | L 6-9 | - | | 35,709 | Brian Moehler | Ben Sheets | Ben Sheets | Brian Moehler | | 306 | 322 | -16 |
| 2008-06-13 | vs NYA | 68 | L 1-2 | - | | 43,095 | Shawn Chacon | Joba Chamberlain | Jose Veras | Doug Brocail | Kyle Farnsworth | 307 | 324 | -17 |
| 2008-06-14 | vs NYA | 69 | L 4-8 | - | | 43,409 | Wandy Rodriguez | Mike Mussina | Mike Mussina | Wandy Rodriguez | | 311 | 332 | -21 |
| 2008-06-15 | vs NYA | 70 | L 0-13 | - | | 43,165 | Roy Oswalt | Chien-Ming Wang | Chien-Ming Wang | Roy Oswalt | | 311 | 345 | -34 |
| 2008-06-17 | @ BAL | 71 | L 5-6 | - | | 21,535 | Brandon Backe | Garrett Olson | Jim Johnson | Doug Brocail | George Sherrill | 316 | 351 | -35 |
| 2008-06-18 | @ BAL | 72 | L 1-2 | - | | 21,112 | Brian Moehler | Jeremy Guthrie | Chad Bradford | Jose Valverde | | 317 | 353 | -36 |
| 2008-06-19 | @ BAL | 73 | L 5-7 | - | | 31,480 | Shawn Chacon | Brian Burres | Brian Burres | Shawn Chacon | George Sherrill | 322 | 360 | -38 |
| 2008-06-20 | @ TBA | 74 | W 4-3 | - | | 14,741 | Roy Oswalt | Matt Garza | Roy Oswalt | Matt Garza | Jose Valverde | 326 | 363 | -37 |
| 2008-06-21 | @ TBA | 75 | L 3-4 | - | | 29,953 | Wandy Rodriguez | Edwin Jackson | Dan Wheeler | Doug Brocail | | 329 | 367 | -38 |
| 2008-06-22 | @ TBA | 76 | W 3-2 | - | | 19,778 | Brandon Backe | Scott Kazmir | Brandon Backe | Scott Kazmir | Jose Valverde | 332 | 369 | -37 |
| 2008-06-24 | vs TEX | 77 | W 4-3 | - | | 40,052 | Brian Moehler | Eric Hurley | Brian Moehler | Eric Hurley | Jose Valverde | 336 | 372 | -36 |
| 2008-06-25 | vs TEX | 78 | L 2-3 | - | | 32,567 | Roy Oswalt | Scott Feldman | Luis Mendoza | Roy Oswalt | C.J. Wilson | 338 | 375 | -37 |
| 2008-06-26 | vs TEX | 79 | W 7-2 | - | | 36,506 | Wandy Rodriguez | Kevin Millwood | Wandy Rodriguez | Kevin Millwood | | 345 | 377 | -32 |
| 2008-06-27 | vs BOS | 80 | L 1-6 | - | | 42,327 | Runelvys Hernandez | Daisuke Matsuzaka | Daisuke Matsuzaka | Runelvys Hernandez | Jonathan Papelbon | 346 | 383 | -37 |
| 2008-06-28 | vs BOS | 81 | W 11-10 | - | | 43,073 | Brandon Backe | Jon Lester | Doug Brocail | Manny Delcarmen | Jose Valverde | 357 | 393 | -36 |
| 2008-06-29 | vs BOS | 82 | W 3-2 | - | | 42,066 | Brian Moehler | Josh Beckett | Doug Brocail | David Aardsma | Jose Valverde | 360 | 395 | -35 |
| 2008-06-30 | vs LAN | 83 | W 4-1 | - | | 28,827 | Roy Oswalt | Eric Stults | Roy Oswalt | Eric Stults | Jose Valverde | 364 | 396 | -32 |
| 2008-07-01 | vs LAN | 84 | L 6-7 | - | | 31,914 | Wandy Rodriguez | Clayton Kershaw | Chan Ho Park | Wesley Wright | Takashi Saito | 370 | 403 | -33 |
| 2008-07-02 | vs LAN | 85 | L 1-4 | - | | 34,058 | Runelvys Hernandez | Hiroki Kuroda | Hiroki Kuroda | Runelvys Hernandez | | 371 | 407 | -36 |
| 2008-07-03 | vs LAN | 86 | L 2-5 | - | | 35,696 | Brandon Backe | Chad Billingsley | Chad Billingsley | Brandon Backe | Takashi Saito | 373 | 412 | -39 |
| 2008-07-04 | @ ATL | 87 | L 2-6 | - | | 48,045 | Brian Moehler | Tim Hudson | Tim Hudson | Brian Moehler | | 375 | 418 | -43 |
| 2008-07-05 | @ ATL | 88 | W 6-1 | - | | 37,049 | Chris Sampson | Jo-Jo Reyes | Chris Sampson | Jo-Jo Reyes | | 381 | 419 | -38 |
| 2008-07-06 | @ ATL | 89 | L 6-7 | - | | 24,169 | Wandy Rodriguez | Charlie Morton | Royce Ring | Tim Byrdak | | 387 | 426 | -39 |
| 2008-07-07 | @ PIT | 90 | L 7-10 | - | | 13,323 | Runelvys Hernandez | Phil Dumatrait | Denny Bautista | Runelvys Hernandez | Damaso Marte | 394 | 436 | -42 |
| 2008-07-08 | @ PIT | 91 | L 3-4 | - | | 17,867 | Brandon Backe | Ian Snell | John Grabow | Doug Brocail | Damaso Marte | 397 | 440 | -43 |
| 2008-07-09 | @ PIT | 92 | W 6-4 | - | | 13,884 | Brian Moehler | John Van Benschoten | Brian Moehler | Sean Burnett | Jose Valverde | 403 | 444 | -41 |
| 2008-07-11 | @ WAS | 93 | L 0-10 | - | | 33,653 | Roy Oswalt | Tim Redding | Tim Redding | Chad Paronto | Steven Shell | 403 | 454 | -51 |
| 2008-07-12 | @ WAS | 94 | W 6-4 | - | | 30,682 | Wandy Rodriguez | Collin Balester | Wandy Rodriguez | Collin Balester | Jose Valverde | 409 | 458 | -49 |
| 2008-07-13 | @ WAS | 95 | W 5-0 | - | | 31,463 | Brandon Backe | Odalis Perez | Brandon Backe | Odalis Perez | | 414 | 458 | -44 |
| 2008-07-18 | vs CHN | 96 | W 2-1 | - | | 42,368 | Brian Moehler | Ted Lilly | Geoff Geary | Bob Howry | | 416 | 459 | -43 |
| 2008-07-19 | vs CHN | 97 | W 4-1 | - | | 43,129 | Wandy Rodriguez | Carlos Zambrano | Wandy Rodriguez | Carlos Zambrano | Jose Valverde | 420 | 460 | -40 |
| 2008-07-20 | vs CHN | 98 | L 0-9 | - | | 41,461 | Brandon Backe | Ryan Dempster | Ryan Dempster | Brandon Backe | | 420 | 469 | -49 |
| 2008-07-21 | vs PIT | 99 | L 3-9 | - | | 34,624 | Runelvys Hernandez | John Van Benschoten | Tyler Yates | Jose Valverde | | 423 | 478 | -55 |
| 2008-07-22 | vs PIT | 100 | L 2-8 | - | | 33,996 | Jack Cassel | Paul Maholm | Paul Maholm | Jack Cassel | | 425 | 486 | -61 |
| 2008-07-23 | vs PIT | 101 | L 7-8 | - | | 36,091 | Brian Moehler | Ian Snell | Franquelis Osoria | Geoff Geary | Damaso Marte | 432 | 494 | -62 |
| 2008-07-25 | @ MIL | 102 | W 3-1 | - | | 41,357 | Wandy Rodriguez | Manny Parra | Wandy Rodriguez | Manny Parra | Jose Valverde | 435 | 495 | -60 |
| 2008-07-26 | @ MIL | 103 | L 4-6 | - | | 43,489 | Brandon Backe | David Bush | Eric Gagne | Doug Brocail | Salomon Torres | 439 | 501 | -62 |
| 2008-07-27 | @ MIL | 104 | W 11-6 | - | | 41,565 | Randy Wolf | Jeff Suppan | Chris Sampson | Jeff Suppan | | 450 | 507 | -57 |
| 2008-07-28 | vs CIN | 105 | W 5-4 | - | | 31,783 | Roy Oswalt | Johnny Cueto | Roy Oswalt | Johnny Cueto | Jose Valverde | 455 | 511 | -56 |
| 2008-07-29 | vs CIN | 106 | W 6-2 | - | | 34,015 | Brian Moehler | Bronson Arroyo | Brian Moehler | Bronson Arroyo | Wesley Wright | 461 | 513 | -52 |
| 2008-07-30 | vs CIN | 107 | L 5-9 | - | | 30,272 | Wandy Rodriguez | Edinson Volquez | Edinson Volquez | Wandy Rodriguez | | 466 | 522 | -56 |
| 2008-08-01 | vs NYN | 108 | W 7-3 | - | | 41,083 | Brandon Backe | Pedro Martinez | Doug Brocail | Aaron Heilman | | 473 | 525 | -52 |
| 2008-08-02 | vs NYN | 109 | W 5-4 | - | | 39,152 | Roy Oswalt | Johan Santana | Jose Valverde | Aaron Heilman | | 478 | 529 | -51 |
| 2008-08-03 | vs NYN | 110 | W 4-0 | - | | 38,602 | Randy Wolf | Oliver Perez | Randy Wolf | Oliver Perez | | 482 | 529 | -47 |
| 2008-08-04 | @ CHN | 111 | W 2-0 | - | | 40,867 | Brian Moehler | Ryan Dempster | Brian Moehler | Ryan Dempster | LaTroy Hawkins | 484 | 529 | -45 |
| 2008-08-05 | @ CHN | 112 | L 7-11 | - | | 40,416 | Wandy Rodriguez | Rich Harden | Bob Howry | Chris Sampson | | 491 | 540 | -49 |
| 2008-08-06 | @ CHN | 113 | L 4-11 | - | | 41,107 | Brandon Backe | Jason Marquis | Jason Marquis | Brandon Backe | | 495 | 551 | -56 |
| 2008-08-07 | @ CIN | 114 | W 7-4 | - | | 27,378 | Roy Oswalt | Josh Fogg | Roy Oswalt | Josh Fogg | | 502 | 555 | -53 |
| 2008-08-08 | @ CIN | 115 | W 9-5 | - | | 25,652 | Randy Wolf | Johnny Cueto | Chris Sampson | Francisco Cordero | | 511 | 560 | -49 |
| 2008-08-09 | @ CIN | 116 | W 3-1 | - | | 26,044 | Brian Moehler | Bronson Arroyo | Brian Moehler | Bronson Arroyo | Jose Valverde | 514 | 561 | -47 |
| 2008-08-10 | @ CIN | 117 | W 13-4 | - | | 30,789 | Wandy Rodriguez | Aaron Harang | Wandy Rodriguez | Aaron Harang | | 527 | 565 | -38 |
| 2008-08-11 | vs SFN | 118 | W 3-1 | - | | 28,220 | Brandon Backe | Jonathan Sanchez | Brandon Backe | Jonathan Sanchez | Jose Valverde | 530 | 566 | -36 |
| 2008-08-12 | vs SFN | 119 | W 12-4 | - | | 29,451 | Roy Oswalt | Tim Lincecum | Roy Oswalt | Tyler Walker | | 542 | 570 | -28 |
| 2008-08-13 | vs SFN | 120 | W 6-2 | - | | 30,330 | Randy Wolf | Barry Zito | Randy Wolf | Barry Zito | | 548 | 572 | -24 |
| 2008-08-14 | vs SFN | 121 | W 7-4 | - | | 33,612 | Brian Moehler | Kevin Correia | LaTroy Hawkins | Keiichi Yabu | Jose Valverde | 555 | 576 | -21 |
| 2008-08-15 | vs ARI | 122 | L 2-12 | - | | 36,035 | Wandy Rodriguez | Brandon Webb | Brandon Webb | Wandy Rodriguez | | 557 | 588 | -31 |
| 2008-08-16 | vs ARI | 123 | L 5-11 | - | | 39,501 | Brandon Backe | Yusmeiro Petit | Yusmeiro Petit | Brandon Backe | | 562 | 599 | -37 |
| 2008-08-17 | vs ARI | 124 | W 3-0 | - | | 42,619 | Roy Oswalt | Randy Johnson | Roy Oswalt | Randy Johnson | Jose Valverde | 565 | 599 | -34 |
| 2008-08-18 | @ MIL | 125 | L 3-9 | - | | 41,991 | Randy Wolf | CC Sabathia | CC Sabathia | Randy Wolf | | 568 | 608 | -40 |
| 2008-08-19 | @ MIL | 126 | W 5-2 | - | | 41,622 | Brian Moehler | Ben Sheets | Brian Moehler | Ben Sheets | Jose Valverde | 573 | 610 | -37 |
| 2008-08-20 | @ MIL | 127 | L 2-5 | - | | 41,419 | Wandy Rodriguez | Manny Parra | Manny Parra | Wandy Rodriguez | Salomon Torres | 575 | 615 | -40 |
| 2008-08-22 | @ NYN | 128 | L 0-3 | - | | 52,008 | Roy Oswalt | Johan Santana | Johan Santana | Roy Oswalt | Luis Ayala | 575 | 618 | -43 |
| 2008-08-23 | @ NYN | 129 | W 8-3 | - | | 51,766 | Brandon Backe | John Maine | Brandon Backe | John Maine | | 583 | 621 | -38 |
| 2008-08-24 | @ NYN | 130 | W 6-4 | - | | 49,758 | Randy Wolf | Oliver Perez | LaTroy Hawkins | Pedro Feliciano | Jose Valverde | 589 | 625 | -36 |
| 2008-08-25 | @ NYN | 131 | L 1-9 | - | | 49,791 | Brian Moehler | Mike Pelfrey | Mike Pelfrey | Brian Moehler | | 590 | 634 | -44 |
| 2008-08-26 | vs CIN | 132 | L 1-2 | - | | 30,395 | Wandy Rodriguez | Bronson Arroyo | Bronson Arroyo | Geoff Geary | | 591 | 636 | -45 |
| 2008-08-27 | vs CIN | 133 | W 4-1 | - | | 30,741 | Roy Oswalt | Josh Fogg | Roy Oswalt | Josh Fogg | Jose Valverde | 595 | 637 | -42 |
| 2008-08-28 | vs CIN | 134 | W 3-2 | - | | 30,028 | Brandon Backe | Aaron Harang | Brandon Backe | Aaron Harang | Jose Valverde | 598 | 639 | -41 |
| 2008-08-29 | vs SLN | 135 | W 3-2 | - | | 33,347 | Randy Wolf | Kyle Lohse | Doug Brocail | Russ Springer | | 601 | 641 | -40 |
| 2008-08-30 | vs SLN | 136 | W 8-5 | - | | 37,569 | Brian Moehler | Braden Looper | Brian Moehler | Braden Looper | Jose Valverde | 609 | 646 | -37 |
| 2008-08-31 | vs SLN | 137 | W 3-0 | - | | 35,638 | Wandy Rodriguez | Todd Wellemeyer | Wandy Rodriguez | Todd Wellemeyer | Jose Valverde | 612 | 646 | -34 |
| 2008-09-01 | @ CHN | 138 | W 3-0 | - | | 40,670 | Roy Oswalt | Jason Marquis | Roy Oswalt | Jason Marquis | Jose Valverde | 615 | 646 | -31 |
| 2008-09-02 | @ CHN | 139 | W 9-7 | - | | 39,846 | Brandon Backe | Carlos Zambrano | Wesley Wright | Kerry Wood | Jose Valverde | 624 | 653 | -29 |
| 2008-09-03 | @ CHN | 140 | W 4-0 | - | | 40,163 | Randy Wolf | Ryan Dempster | Randy Wolf | Ryan Dempster | | 628 | 653 | -25 |
| 2008-09-05 | @ COL | 141 | L 3-5 | - | | 26,163 | Brian Moehler | Ubaldo Jimenez | Ubaldo Jimenez | Brian Moehler | Brian Fuentes | 631 | 658 | -27 |
| 2008-09-06 | @ COL | 142 | W 2-0 | - | | 32,352 | Roy Oswalt | Jeff Francis | Roy Oswalt | Jeff Francis | | 633 | 658 | -25 |
| 2008-09-07 | @ COL | 143 | W 7-5 | - | | 30,509 | Wandy Rodriguez | Jorge de la Rosa | Doug Brocail | Taylor Buchholz | Jose Valverde | 640 | 663 | -23 |
| 2008-09-08 | vs PIT | 144 | W 3-2 | - | | 26,526 | Alberto Arias | Ian Snell | Alberto Arias | Ian Snell | Jose Valverde | 643 | 665 | -22 |
| 2008-09-09 | vs PIT | 145 | W 9-3 | - | | 30,034 | Randy Wolf | Ross Ohlendorf | Randy Wolf | Ross Ohlendorf | | 652 | 668 | -16 |
| 2008-09-10 | vs PIT | 146 | W 7-4 | - | | 26,859 | Brian Moehler | Tom Gorzelanny | Brian Moehler | Denny Bautista | Jose Valverde | 659 | 672 | -13 |
| 2008-09-11 | vs PIT | 147 | W 6-0 | - | | 31,101 | Roy Oswalt | Zach Duke | Roy Oswalt | Zach Duke | | 665 | 672 | -7 |
| 2008-09-14 | vs CHN | 148 | L 0-5 | - | | 23,441 | Randy Wolf | Carlos Zambrano | Carlos Zambrano | Randy Wolf | | 665 | 677 | -12 |
| 2008-09-15 | vs CHN | 149 | L 1-6 | - | | 15,158 | Brian Moehler | Ted Lilly | Ted Lilly | Brian Moehler | | 666 | 683 | -17 |
| 2008-09-16 | @ FLO | 150 | L 1-5 | - | | 12,232 | Roy Oswalt | Chris Volstad | Chris Volstad | Roy Oswalt | | 667 | 688 | -21 |
| 2008-09-17 | @ FLO | 151 | L 2-14 | - | | 14,124 | Brandon Backe | Ricky Nolasco | Ricky Nolasco | Brandon Backe | | 669 | 702 | -33 |
| 2008-09-18 | @ FLO | 152 | L 1-8 | - | | 14,219 | Alberto Arias | Scott Olsen | Scott Olsen | Alberto Arias | | 670 | 710 | -40 |
| 2008-09-19 | @ PIT | 153 | W 5-1 | - | | 26,301 | Randy Wolf | Ian Snell | Randy Wolf | Ian Snell | | 675 | 711 | -36 |
| 2008-09-20 | @ PIT | 154 | L 4-6 | - | | 36,621 | Brian Moehler | Jimmy Barthmaier | Jason Davis | Brian Moehler | Matt Capps | 679 | 717 | -38 |
| 2008-09-21 | @ PIT | 155 | W 6-2 | - | | 20,311 | Roy Oswalt | Ross Ohlendorf | Roy Oswalt | Ross Ohlendorf | | 685 | 719 | -34 |
| 2008-09-23 | vs CIN | 156 | L 1-2 | - | | 27,561 | Wandy Rodriguez | Edinson Volquez | Edinson Volquez | Wandy Rodriguez | Francisco Cordero | 686 | 721 | -35 |
| 2008-09-24 | vs CIN | 157 | W 5-0 | - | | 26,103 | Randy Wolf | Ramon Ramirez | Randy Wolf | Ramon Ramirez | | 691 | 721 | -30 |
| 2008-09-25 | vs CIN | 158 | W 8-6 | - | | 31,204 | Roy Oswalt | Johnny Cueto | Roy Oswalt | Johnny Cueto | Jose Valverde | 699 | 727 | -28 |
| 2008-09-26 | vs ATL | 159 | W 5-4 | - | | 33,477 | Brian Moehler | Jorge Campillo | Jose Valverde | Julian Tavarez | | 704 | 731 | -27 |
| 2008-09-27 | vs ATL | 160 | L 5-11 | - | | 37,491 | Brandon Backe | James Parr | Vladimir Nunez | Brandon Backe | | 709 | 742 | -33 |
| 2008-09-28 | vs ATL | 161 | W 3-1 | - | | 37,113 | Wandy Rodriguez | Mike Hampton | Wandy Rodriguez | Mike Hampton | Jose Valverde | 712 | 743 | -31 |