| 2008-04-01 | @ SLN | 1 | W 2-1 | 1-0 | 2 | 45,996 | Kip Wells | Kyle Lohse | Taylor Buchholz | Ryan Franklin | Manuel Corpas | 2 | 1 | 1 |
| 2008-04-02 | @ SLN | 2 | L 3-8 | 1-1 | 4 | 39,915 | Aaron Cook | Todd Wellemeyer | Todd Wellemeyer | Aaron Cook | | 5 | 9 | -4 |
| 2008-04-03 | @ SLN | 3 | L 0-3 | 1-2 | 4 | 33,748 | Ubaldo Jimenez | Brad Thompson | Brad Thompson | Ubaldo Jimenez | Jason Isringhausen | 5 | 12 | -7 |
| 2008-04-04 | vs ARI | 4 | L 1-8 | 1-3 | 4 | 49,233 | Mark Redman | Micah Owings | Micah Owings | Mark Redman | | 6 | 20 | -14 |
| 2008-04-05 | vs ARI | 5 | L 2-7 | 1-4 | 4 | 43,124 | Jeff Francis | Brandon Webb | Brandon Webb | Jeff Francis | | 8 | 27 | -19 |
| 2008-04-06 | vs ARI | 6 | L 2-5 | 1-5 | 4 | 42,865 | Franklin Morales | Edgar Gonzalez | Brandon Lyon | Micah Bowie | Chad Qualls | 10 | 32 | -22 |
| 2008-04-07 | vs ATL | 7 | W 2-1 | 2-5 | 4 | 24,304 | Aaron Cook | Tom Glavine | Matt Herges | Blaine Boyer | Manuel Corpas | 12 | 33 | -21 |
| 2008-04-08 | vs ATL | 8 | W 4-3 | 3-5 | 4 | 24,640 | Ubaldo Jimenez | Jair Jurrjens | Ubaldo Jimenez | Jair Jurrjens | Manuel Corpas | 16 | 36 | -20 |
| 2008-04-09 | vs ATL | 9 | W 12-6 | 4-5 | 3 | 23,210 | Mark Redman | Chuck James | Mark Redman | Chuck James | | 28 | 42 | -14 |
| 2008-04-11 | @ ARI | 10 | L 2-8 | 4-6 | 3 | 31,732 | Jeff Francis | Brandon Webb | Brandon Webb | Jeff Francis | | 30 | 50 | -20 |
| 2008-04-12 | @ ARI | 11 | L 3-10 | 4-7 | 4 | 29,256 | Franklin Morales | Dan Haren | Dan Haren | Franklin Morales | | 33 | 60 | -27 |
| 2008-04-13 | @ ARI | 12 | W 13-5 | 5-7 | 3 | 31,321 | Aaron Cook | Edgar Gonzalez | Aaron Cook | Edgar Gonzalez | | 46 | 65 | -19 |
| 2008-04-15 | @ SDN | 13 | L 0-6 | 5-8 | 5 | 24,439 | Ubaldo Jimenez | Randy Wolf | Randy Wolf | Ubaldo Jimenez | | 46 | 71 | -25 |
| 2008-04-16 | @ SDN | 14 | W 10-2 | 6-8 | 4 | 21,730 | Mark Redman | Justin Germano | Mark Redman | Justin Germano | | 56 | 73 | -17 |
| 2008-04-17 | @ SDN | 15 | W 2-1 | 7-8 | 3 | 25,984 | Jeff Francis | Jake Peavy | Kip Wells | Glendon Rusch | | 58 | 74 | -16 |
| 2008-04-18 | @ HOU | 16 | W 11-5 | 8-8 | 2 | 34,272 | Franklin Morales | Chris Sampson | Franklin Morales | Chris Sampson | | 69 | 79 | -10 |
| 2008-04-19 | @ HOU | 17 | W 3-2 | 9-8 | 2 | 34,540 | Aaron Cook | Wandy Rodriguez | Aaron Cook | Oscar Villarreal | Manuel Corpas | 72 | 81 | -9 |
| 2008-04-20 | @ HOU | 18 | L 4-6 | 9-9 | 2 | 35,286 | Ubaldo Jimenez | Shawn Chacon | Wesley Wright | Brian Fuentes | Jose Valverde | 76 | 87 | -11 |
| 2008-04-21 | vs PHI | 19 | L 5-9 | 9-10 | 2 | 24,886 | Mark Redman | Kyle Kendrick | Rudy Seanez | Taylor Buchholz | | 81 | 96 | -15 |
| 2008-04-22 | vs PHI | 20 | L 6-8 | 9-11 | 2 | 26,665 | Jeff Francis | Brett Myers | Ryan Madson | Manuel Corpas | Brad Lidge | 87 | 104 | -17 |
| 2008-04-23 | vs CHN | 21 | L 6-7 | 9-12 | 2 | 36,864 | Franklin Morales | Rich Hill | Kerry Wood | Kip Wells | Carlos Marmol | 93 | 111 | -18 |
| 2008-04-24 | vs CHN | 22 | W 4-2 | 10-12 | 2 | 32,791 | Aaron Cook | Jason Marquis | Aaron Cook | Kevin Hart | Brian Fuentes | 97 | 113 | -16 |
| 2008-04-25 | @ LAN | 23 | L 7-8 | 10-13 | 3 | 53,205 | Ubaldo Jimenez | Hiroki Kuroda | Chan Ho Park | Taylor Buchholz | | 104 | 121 | -17 |
| 2008-04-26 | @ LAN | 24 | L 3-11 | 10-14 | 4 | 50,469 | Mark Redman | Brad Penny | Brad Penny | Mark Redman | | 107 | 132 | -25 |
| 2008-04-27 | @ LAN | 25 | L 2-3 | 10-15 | 4 | 50,670 | Jeff Francis | Esteban Loaiza | Joe Beimel | Manuel Corpas | | 109 | 135 | -26 |
| 2008-04-28 | @ SFN | 26 | L 0-4 | 10-16 | 4 | 30,153 | Franklin Morales | Matt Cain | Matt Cain | Franklin Morales | | 109 | 139 | -30 |
| 2008-04-29 | @ SFN | 27 | W 3-2 | 11-16 | 4 | 32,176 | Aaron Cook | Tim Lincecum | Aaron Cook | Tim Lincecum | Brian Fuentes | 112 | 141 | -29 |
| 2008-04-30 | @ SFN | 28 | L 2-3 | 11-17 | 4 | 30,509 | Ubaldo Jimenez | Jonathan Sanchez | Merkin Valdez | Ryan Speier | Brian Wilson | 114 | 144 | -30 |
| 2008-05-02 | vs LAN | 29 | L 6-11 | 11-18 | 4 | 30,291 | Jeff Francis | Brad Penny | Brad Penny | Jeff Francis | | 120 | 155 | -35 |
| 2008-05-03 | vs LAN | 30 | L 7-12 | 11-19 | 5 | 38,597 | Jorge de la Rosa | Esteban Loaiza | Hong-Chih Kuo | Jorge de la Rosa | | 127 | 167 | -40 |
| 2008-05-04 | vs LAN | 31 | W 7-2 | 12-19 | 4 | 43,726 | Aaron Cook | Derek Lowe | Aaron Cook | Derek Lowe | Taylor Buchholz | 134 | 169 | -35 |
| 2008-05-05 | vs SLN | 32 | L 5-6 | 12-20 | 4 | 28,183 | Ubaldo Jimenez | Joel Pineiro | Randy Flores | Brian Fuentes | Jason Isringhausen | 139 | 175 | -36 |
| 2008-05-06 | vs SLN | 33 | L 5-6 | 12-21 | 4 | 25,460 | Mark Redman | Braden Looper | Braden Looper | Mark Redman | Ryan Franklin | 144 | 181 | -37 |
| 2008-05-07 | vs SLN | 34 | W 4-3 | 13-21 | 4 | 25,432 | Jeff Francis | Adam Wainwright | Ryan Speier | Jason Isringhausen | Brian Fuentes | 148 | 184 | -36 |
| 2008-05-08 | vs SLN | 35 | W 9-3 | 14-21 | 3 | 25,376 | Jorge de la Rosa | Kyle Lohse | Jorge de la Rosa | Kyle Lohse | | 157 | 187 | -30 |
| 2008-05-09 | @ SDN | 36 | W 4-2 | 15-21 | 3 | 31,057 | Aaron Cook | Jake Peavy | Aaron Cook | Jake Peavy | Brian Fuentes | 161 | 189 | -28 |
| 2008-05-10 | @ SDN | 37 | L 2-3 | 15-22 | 3 | 34,117 | Ubaldo Jimenez | Greg Maddux | Greg Maddux | Ubaldo Jimenez | Trevor Hoffman | 163 | 192 | -29 |
| 2008-05-11 | @ SDN | 38 | L 1-6 | 15-23 | 4 | 28,624 | Greg Reynolds | Chris Young | Chris Young | Greg Reynolds | | 164 | 198 | -34 |
| 2008-05-13 | @ ARI | 39 | L 4-8 | 15-24 | 4 | 27,292 | Jeff Francis | Randy Johnson | Randy Johnson | Jeff Francis | | 168 | 206 | -38 |
| 2008-05-14 | @ ARI | 40 | L 3-4 | 15-25 | 4 | 23,127 | Jorge de la Rosa | Micah Owings | Micah Owings | Jorge de la Rosa | Brandon Lyon | 171 | 210 | -39 |
| 2008-05-15 | @ ARI | 41 | L 5-8 | 15-26 | 4 | 21,447 | Aaron Cook | Brandon Webb | Brandon Webb | Aaron Cook | Brandon Lyon | 176 | 218 | -42 |
| 2008-05-16 | vs MIN | 42 | L 2-4 | 15-27 | 5 | 35,336 | Ubaldo Jimenez | Nick Blackburn | Nick Blackburn | Ubaldo Jimenez | Joe Nathan | 178 | 222 | -44 |
| 2008-05-17 | vs MIN | 43 | W 3-2 | 16-27 | 4 | 43,149 | Greg Reynolds | Livan Hernandez | Matt Herges | Livan Hernandez | Brian Fuentes | 181 | 224 | -43 |
| 2008-05-18 | vs MIN | 44 | W 6-2 | 17-27 | 3 | 40,326 | Jeff Francis | Kevin Slowey | Jeff Francis | Kevin Slowey | | 187 | 226 | -39 |
| 2008-05-19 | vs SFN | 45 | W 4-3 | 18-27 | 3 | 28,362 | Jorge de la Rosa | Pat Misch | Jason Grilli | Vinnie Chulk | Brian Fuentes | 191 | 229 | -38 |
| 2008-05-20 | vs SFN | 46 | L 5-6 | 18-28 | 3 | 28,361 | Aaron Cook | Tim Lincecum | Tim Lincecum | Aaron Cook | Brian Wilson | 196 | 235 | -39 |
| 2008-05-21 | vs SFN | 47 | L 2-3 | 18-29 | 4 | 27,081 | Ubaldo Jimenez | Jonathan Sanchez | Tyler Walker | Matt Herges | Brian Wilson | 198 | 238 | -40 |
| 2008-05-23 | vs NYN | 48 | W 6-5 | 19-29 | 4 | 33,341 | Greg Reynolds | Oliver Perez | Taylor Buchholz | Aaron Heilman | | 204 | 243 | -39 |
| 2008-05-24 | vs NYN | 49 | L 2-9 | 19-30 | 4 | 38,142 | Jeff Francis | Claudio Vargas | Claudio Vargas | Jeff Francis | | 206 | 252 | -46 |
| 2008-05-25 | vs NYN | 50 | W 4-1 | 20-30 | 3 | 42,123 | Aaron Cook | John Maine | Aaron Cook | John Maine | | 210 | 253 | -43 |
| 2008-05-26 | @ PHI | 51 | L 5-20 | 20-31 | 3 | 44,764 | Jorge de la Rosa | Jamie Moyer | Jamie Moyer | Jorge de la Rosa | | 215 | 273 | -58 |
| 2008-05-27 | @ PHI | 52 | L 4-7 | 20-32 | 4 | 34,716 | Ubaldo Jimenez | Kyle Kendrick | Kyle Kendrick | Ubaldo Jimenez | | 219 | 280 | -61 |
| 2008-05-28 | @ PHI | 53 | L 1-6 | 20-33 | 4 | 39,845 | Greg Reynolds | Adam Eaton | Adam Eaton | Greg Reynolds | | 220 | 286 | -66 |
| 2008-05-29 | @ CHN | 54 | L 4-8 | 20-34 | 5 | 39,851 | Jeff Francis | Jason Marquis | Michael Wuertz | Matt Herges | | 224 | 294 | -70 |
| 2008-05-30 | @ CHN | 55 | L 9-10 | 20-35 | 5 | 39,686 | Aaron Cook | Ted Lilly | Scott Eyre | Manuel Corpas | Kerry Wood | 233 | 304 | -71 |
| 2008-05-31 | @ CHN | 56 | L 4-5 | 20-36 | 5 | 41,529 | Glendon Rusch | Ryan Dempster | Ryan Dempster | Glendon Rusch | Carlos Marmol | 237 | 309 | -72 |
| 2008-06-01 | @ CHN | 57 | L 3-5 | 20-37 | 5 | 41,730 | Ubaldo Jimenez | Sean Gallagher | Sean Gallagher | Ubaldo Jimenez | Kerry Wood | 240 | 314 | -74 |
| 2008-06-02 | @ LAN | 58 | L 2-8 | 20-38 | 5 | 39,098 | Greg Reynolds | Derek Lowe | Derek Lowe | Greg Reynolds | | 242 | 322 | -80 |
| 2008-06-03 | @ LAN | 59 | W 3-0 | 21-38 | 5 | 38,548 | Jeff Francis | Brad Penny | Jeff Francis | Brad Penny | Brian Fuentes | 245 | 322 | -77 |
| 2008-06-04 | @ LAN | 60 | W 2-1 | 22-38 | 5 | 36,393 | Aaron Cook | Clayton Kershaw | Aaron Cook | Clayton Kershaw | Brian Fuentes | 247 | 323 | -76 |
| 2008-06-06 | vs MIL | 61 | W 6-4 | 23-38 | 5 | 30,558 | Ubaldo Jimenez | Ben Sheets | Manuel Corpas | Guillermo Mota | Brian Fuentes | 253 | 327 | -74 |
| 2008-06-07 | vs MIL | 62 | W 7-2 | 24-38 | 5 | 37,283 | Greg Reynolds | David Bush | Greg Reynolds | David Bush | | 260 | 329 | -69 |
| 2008-06-08 | vs MIL | 63 | L 2-3 | 24-39 | 5 | 32,256 | Jeff Francis | Jeff Suppan | Jeff Suppan | Jeff Francis | Salomon Torres | 262 | 332 | -70 |
| 2008-06-10 | vs SFN | 64 | W 10-5 | 25-39 | 5 | 28,359 | Aaron Cook | Pat Misch | Aaron Cook | Pat Misch | | 272 | 337 | -65 |
| 2008-06-11 | vs SFN | 65 | W 1-0 | 26-39 | 5 | 26,235 | Ubaldo Jimenez | Tim Lincecum | Brian Fuentes | Keiichi Yabu | | 273 | 337 | -64 |
| 2008-06-12 | vs SFN | 66 | L 7-10 | 26-40 | 5 | 30,376 | Greg Reynolds | Jonathan Sanchez | Jonathan Sanchez | Greg Reynolds | Brian Wilson | 280 | 347 | -67 |
| 2008-06-13 | @ CHA | 67 | L 4-5 | 26-41 | 5 | 30,143 | Jeff Francis | Gavin Floyd | Matt Thornton | Matt Herges | Bobby Jenks | 284 | 352 | -68 |
| 2008-06-14 | @ CHA | 68 | W 2-0 | 27-41 | 5 | 35,663 | Jorge de la Rosa | John Danks | Jason Grilli | Octavio Dotel | Brian Fuentes | 286 | 352 | -66 |
| 2008-06-15 | @ CHA | 69 | W 5-3 | 28-41 | 5 | 32,004 | Aaron Cook | Jose Contreras | Aaron Cook | Jose Contreras | Brian Fuentes | 291 | 355 | -64 |
| 2008-06-16 | vs ATL | 70 | L 1-7 | 28-42 | 5 | 25,120 | Ubaldo Jimenez | Jair Jurrjens | Jair Jurrjens | Ubaldo Jimenez | | 292 | 362 | -70 |
| 2008-06-17 | vs CLE | 71 | W 10-2 | 29-42 | 5 | 28,146 | Greg Reynolds | Paul Byrd | Greg Reynolds | Paul Byrd | | 302 | 364 | -62 |
| 2008-06-18 | vs CLE | 72 | W 4-2 | 30-42 | 5 | 28,339 | Jeff Francis | Aaron Laffey | Jeff Francis | Aaron Laffey | Brian Fuentes | 306 | 366 | -60 |
| 2008-06-19 | vs CLE | 73 | W 6-3 | 31-42 | 3 | 33,174 | Jorge de la Rosa | Jeremy Sowers | Jorge de la Rosa | Jeremy Sowers | Brian Fuentes | 312 | 369 | -57 |
| 2008-06-20 | vs NYN | 74 | L 2-7 | 31-43 | 5 | 30,411 | Aaron Cook | John Maine | John Maine | Aaron Cook | | 314 | 376 | -62 |
| 2008-06-21 | vs NYN | 75 | W 7-1 | 32-43 | 3 | 35,637 | Ubaldo Jimenez | Pedro Martinez | Ubaldo Jimenez | Pedro Martinez | | 321 | 377 | -56 |
| 2008-06-22 | vs NYN | 76 | L 1-3 | 32-44 | 3 | 45,019 | Greg Reynolds | Mike Pelfrey | Mike Pelfrey | Greg Reynolds | Billy Wagner | 322 | 380 | -58 |
| 2008-06-23 | @ KCA | 77 | L 4-8 | 32-45 | 4 | 12,260 | Jeff Francis | Brian Bannister | Brian Bannister | Jeff Francis | | 326 | 388 | -62 |
| 2008-06-24 | @ KCA | 78 | L 3-7 | 32-46 | 4 | 19,169 | Jorge de la Rosa | Zack Greinke | Zack Greinke | Jorge de la Rosa | | 329 | 395 | -66 |
| 2008-06-25 | @ KCA | 79 | L 2-4 | 32-47 | 4 | 16,615 | Aaron Cook | Luke Hochevar | Luke Hochevar | Aaron Cook | Joakim Soria | 331 | 399 | -68 |
| 2008-06-27 | @ DET | 80 | L 1-7 | 32-48 | 4 | 40,842 | Ubaldo Jimenez | Eddie Bonine | Eddie Bonine | Ubaldo Jimenez | | 332 | 406 | -74 |
| 2008-06-28 | @ DET | 81 | L 6-7 | 32-49 | 4 | 42,729 | Jeff Francis | Justin Verlander | Freddy Dolsi | Brian Fuentes | | 338 | 413 | -75 |
| 2008-06-29 | @ DET | 82 | L 3-4 | 32-50 | 4 | 41,305 | Greg Reynolds | Kenny Rogers | Kenny Rogers | Greg Reynolds | Todd Jones | 341 | 417 | -76 |
| 2008-06-30 | vs SDN | 83 | L 8-15 | 32-51 | 5 | 43,248 | Jorge de la Rosa | Greg Maddux | Heath Bell | Brian Fuentes | | 349 | 432 | -83 |
| 2008-07-01 | vs SDN | 84 | W 4-0 | 33-51 | 4 | 26,221 | Aaron Cook | Josh Banks | Aaron Cook | Josh Banks | | 353 | 432 | -79 |
| 2008-07-02 | vs SDN | 85 | W 8-1 | 34-51 | 4 | 28,377 | Ubaldo Jimenez | Randy Wolf | Ubaldo Jimenez | Randy Wolf | | 361 | 433 | -72 |
| 2008-07-03 | vs FLO | 86 | W 6-5 | 35-51 | 4 | 48,084 | Mark Redman | Andrew Miller | Matt Herges | Kevin Gregg | | 367 | 438 | -71 |
| 2008-07-04 | vs FLO | 87 | W 18-17 | 36-51 | 4 | 48,691 | Greg Reynolds | Scott Olsen | Taylor Buchholz | Kevin Gregg | | 385 | 455 | -70 |
| 2008-07-05 | vs FLO | 88 | W 12-6 | 37-51 | 4 | 35,137 | Jorge de la Rosa | Ryan Tucker | Jorge de la Rosa | Ryan Tucker | | 397 | 461 | -64 |
| 2008-07-06 | vs FLO | 89 | L 5-10 | 37-52 | 4 | 27,168 | Aaron Cook | Mark Hendrickson | Chris Volstad | Aaron Cook | | 402 | 471 | -69 |
| 2008-07-07 | @ MIL | 90 | W 4-3 | 38-52 | 4 | 35,161 | Ubaldo Jimenez | Seth McClung | Ubaldo Jimenez | Seth McClung | Brian Fuentes | 406 | 474 | -68 |
| 2008-07-08 | @ MIL | 91 | L 3-7 | 38-53 | 4 | 42,533 | Mark Redman | CC Sabathia | CC Sabathia | Mark Redman | | 409 | 481 | -72 |
| 2008-07-09 | @ MIL | 92 | W 8-3 | 39-53 | 4 | 37,092 | Glendon Rusch | Ben Sheets | Glendon Rusch | Ben Sheets | | 417 | 484 | -67 |
| 2008-07-10 | @ MIL | 93 | L 1-11 | 39-54 | 4 | 43,389 | Jorge de la Rosa | David Bush | David Bush | Jorge de la Rosa | | 418 | 495 | -77 |
| 2008-07-11 | @ NYN | 94 | L 1-2 | 39-55 | 4 | 49,016 | Aaron Cook | Oliver Perez | Pedro Feliciano | Taylor Buchholz | Billy Wagner | 419 | 497 | -78 |
| 2008-07-12 | @ NYN | 95 | L 0-3 | 39-56 | 4 | 54,137 | Ubaldo Jimenez | Pedro Martinez | Carlos Muniz | Ubaldo Jimenez | Billy Wagner | 419 | 500 | -81 |
| 2008-07-13 | @ NYN | 96 | L 0-7 | 39-57 | 4 | 51,293 | Mark Redman | Mike Pelfrey | Mike Pelfrey | Mark Redman | | 419 | 507 | -88 |
| 2008-07-17 | vs PIT | 97 | W 5-3 | 40-57 | 4 | 30,584 | Ubaldo Jimenez | Paul Maholm | Ubaldo Jimenez | Paul Maholm | Brian Fuentes | 424 | 510 | -86 |
| 2008-07-18 | vs PIT | 98 | W 5-2 | 41-57 | 3 | 37,114 | Glendon Rusch | Ian Snell | Glendon Rusch | Ian Snell | Brian Fuentes | 429 | 512 | -83 |
| 2008-07-19 | vs PIT | 99 | W 7-1 | 42-57 | 3 | 44,565 | Jorge de la Rosa | Yoslan Herrera | Jorge de la Rosa | Yoslan Herrera | | 436 | 513 | -77 |
| 2008-07-20 | vs PIT | 100 | W 11-3 | 43-57 | 3 | 30,488 | Aaron Cook | Zach Duke | Aaron Cook | Zach Duke | | 447 | 516 | -69 |
| 2008-07-21 | vs LAN | 101 | L 10-16 | 43-58 | 3 | 38,291 | Kip Wells | Eric Stults | Brian Falkenborg | Kip Wells | | 457 | 532 | -75 |
| 2008-07-22 | vs LAN | 102 | W 10-1 | 44-58 | 3 | 41,567 | Ubaldo Jimenez | Clayton Kershaw | Ubaldo Jimenez | Clayton Kershaw | | 467 | 533 | -66 |
| 2008-07-23 | vs LAN | 103 | W 5-3 | 45-58 | 3 | 36,305 | Glendon Rusch | Hiroki Kuroda | Glendon Rusch | Hiroki Kuroda | Brian Fuentes | 472 | 536 | -64 |
| 2008-07-25 | @ CIN | 104 | W 7-2 | 46-58 | 3 | 27,501 | Aaron Cook | Edinson Volquez | Aaron Cook | Edinson Volquez | | 479 | 538 | -59 |
| 2008-07-26 | @ CIN | 105 | W 5-1 | 47-58 | 3 | 33,981 | Jorge de la Rosa | Homer Bailey | Jorge de la Rosa | Homer Bailey | | 484 | 539 | -55 |
| 2008-07-27 | @ CIN | 106 | W 11-0 | 48-58 | 3 | 28,246 | Ubaldo Jimenez | Josh Fogg | Ubaldo Jimenez | Josh Fogg | | 495 | 539 | -44 |
| 2008-07-28 | @ PIT | 107 | L 4-8 | 48-59 | 3 | 15,303 | Valerio de los Santos | Ian Snell | Ian Snell | Jason Grilli | | 499 | 547 | -48 |
| 2008-07-29 | @ PIT | 108 | L 4-6 | 48-60 | 3 | 17,507 | Glendon Rusch | Yoslan Herrera | Jason Davis | Matt Herges | Tyler Yates | 503 | 553 | -50 |
| 2008-07-30 | @ PIT | 109 | W 7-4 | 49-60 | 3 | 16,587 | Aaron Cook | Zach Duke | Aaron Cook | Zach Duke | Brian Fuentes | 510 | 557 | -47 |
| 2008-07-31 | @ FLO | 110 | L 2-12 | 49-61 | 3 | 13,634 | Jorge de la Rosa | Anibal Sanchez | Anibal Sanchez | Jorge de la Rosa | | 512 | 569 | -57 |
| 2008-08-01 | @ FLO | 111 | W 5-2 | 50-61 | 3 | 16,555 | Ubaldo Jimenez | Chris Volstad | Ubaldo Jimenez | Chris Volstad | Brian Fuentes | 517 | 571 | -54 |
| 2008-08-02 | @ FLO | 112 | L 3-5 | 50-62 | 3 | 22,324 | Valerio de los Santos | Ricky Nolasco | Ricky Nolasco | Valerio de los Santos | Kevin Gregg | 520 | 576 | -56 |
| 2008-08-03 | @ FLO | 113 | W 3-2 | 51-62 | 3 | 14,310 | Glendon Rusch | Scott Olsen | Taylor Buchholz | Joe Nelson | Brian Fuentes | 523 | 578 | -55 |
| 2008-08-04 | vs WAS | 114 | L 4-9 | 51-63 | 3 | 33,143 | Aaron Cook | Tim Redding | Tim Redding | Aaron Cook | | 527 | 587 | -60 |
| 2008-08-05 | vs WAS | 115 | W 8-2 | 52-63 | 3 | 27,483 | Jorge de la Rosa | John Lannan | Manuel Corpas | Luis Ayala | | 535 | 589 | -54 |
| 2008-08-07 | vs WAS | 116 | L 3-6 | 52-65 | 3 | 0 | Jeff Francis | Jason Bergmann | Jason Bergmann | Jeff Francis | Joel Hanrahan | 538 | 595 | -57 |
| 2008-08-07 | vs WAS | 117 | L 3-6 | 52-65 | 3 | 30,448 | Ubaldo Jimenez | Odalis Perez | Odalis Perez | Ubaldo Jimenez | Joel Hanrahan | 541 | 601 | -60 |
| 2008-08-08 | vs SDN | 118 | W 6-3 | 53-65 | 3 | 33,147 | Glendon Rusch | Jake Peavy | Glendon Rusch | Jake Peavy | Brian Fuentes | 547 | 604 | -57 |
| 2008-08-09 | vs SDN | 119 | L 3-8 | 53-66 | 3 | 41,640 | Aaron Cook | Greg Maddux | Greg Maddux | Aaron Cook | Trevor Hoffman | 550 | 612 | -62 |
| 2008-08-10 | vs SDN | 120 | L 7-16 | 53-67 | 3 | 45,660 | Livan Hernandez | Chris Young | Justin Hampson | Livan Hernandez | | 557 | 628 | -71 |
| 2008-08-12 | vs ARI | 121 | L 2-4 | 53-68 | 3 | 31,218 | Ubaldo Jimenez | Randy Johnson | Randy Johnson | Ubaldo Jimenez | Brandon Lyon | 559 | 632 | -73 |
| 2008-08-13 | vs ARI | 122 | W 6-5 | 54-68 | 3 | 30,247 | Jeff Francis | Doug Davis | Taylor Buchholz | Jon Rauch | Brian Fuentes | 565 | 637 | -72 |
| 2008-08-14 | vs ARI | 123 | L 2-6 | 54-69 | 3 | 27,575 | Glendon Rusch | Dan Haren | Dan Haren | Glendon Rusch | | 567 | 643 | -76 |
| 2008-08-15 | @ WAS | 124 | W 4-3 | 55-69 | 3 | 27,965 | Jorge de la Rosa | Tim Redding | Jorge de la Rosa | Tim Redding | Brian Fuentes | 571 | 646 | -75 |
| 2008-08-16 | @ WAS | 125 | W 13-6 | 56-69 | 3 | 28,909 | Livan Hernandez | John Lannan | Livan Hernandez | John Lannan | | 584 | 652 | -68 |
| 2008-08-17 | @ WAS | 126 | W 7-2 | 57-69 | 3 | 31,467 | Aaron Cook | Odalis Perez | Aaron Cook | Odalis Perez | | 591 | 654 | -63 |
| 2008-08-19 | @ LAN | 127 | W 8-3 | 58-69 | 3 | 46,687 | Ubaldo Jimenez | Hiroki Kuroda | Ubaldo Jimenez | Hiroki Kuroda | | 599 | 657 | -58 |
| 2008-08-20 | @ LAN | 128 | W 4-3 | 59-69 | 3 | 48,183 | Jeff Francis | Chad Billingsley | Taylor Buchholz | Jonathan Broxton | Brian Fuentes | 603 | 660 | -57 |
| 2008-08-21 | @ LAN | 129 | L 1-3 | 59-70 | 3 | 44,885 | Jorge de la Rosa | Derek Lowe | Derek Lowe | Jorge de la Rosa | Jonathan Broxton | 604 | 663 | -59 |
| 2008-08-22 | vs CIN | 130 | L 5-8 | 59-71 | 3 | 30,337 | Livan Hernandez | Aaron Harang | Aaron Harang | Livan Hernandez | Francisco Cordero | 609 | 671 | -62 |
| 2008-08-23 | vs CIN | 131 | W 7-6 | 60-71 | 3 | 42,282 | Aaron Cook | Edinson Volquez | Luis Vizcaino | Mike Lincoln | Brian Fuentes | 616 | 677 | -61 |
| 2008-08-24 | vs CIN | 132 | W 4-3 | 61-71 | 3 | 31,173 | Ubaldo Jimenez | Johnny Cueto | Ryan Speier | Mike Lincoln | | 620 | 680 | -60 |
| 2008-08-25 | @ SFN | 133 | W 4-2 | 62-71 | 3 | 31,132 | Jeff Francis | Matt Cain | Jeff Francis | Matt Cain | Brian Fuentes | 624 | 682 | -58 |
| 2008-08-26 | @ SFN | 134 | W 7-2 | 63-71 | 3 | 32,695 | Jorge de la Rosa | Matt Palmer | Jorge de la Rosa | Matt Palmer | Jason Grilli | 631 | 684 | -53 |
| 2008-08-27 | @ SFN | 135 | L 1-4 | 63-72 | 3 | 31,627 | Livan Hernandez | Tim Lincecum | Tim Lincecum | Livan Hernandez | Brian Wilson | 632 | 688 | -56 |
| 2008-08-29 | @ SDN | 136 | W 9-4 | 64-72 | 3 | 25,274 | Aaron Cook | Dirk Hayhurst | Aaron Cook | Dirk Hayhurst | | 641 | 692 | -51 |
| 2008-08-30 | @ SDN | 137 | L 4-9 | 64-73 | 3 | 30,240 | Ubaldo Jimenez | Josh Geer | Josh Geer | Ubaldo Jimenez | | 645 | 701 | -56 |
| 2008-08-31 | @ SDN | 138 | L 1-2 | 64-74 | 3 | 26,395 | Jeff Francis | Jake Peavy | Trevor Hoffman | Taylor Buchholz | | 646 | 703 | -57 |
| 2008-09-01 | vs SFN | 139 | W 4-0 | 65-74 | 3 | 31,388 | Jorge de la Rosa | Jonathan Sanchez | Jorge de la Rosa | Jonathan Sanchez | | 650 | 703 | -53 |
| 2008-09-02 | vs SFN | 140 | W 6-5 | 66-74 | 3 | 23,710 | Livan Hernandez | Tim Lincecum | Jason Grilli | Keiichi Yabu | | 656 | 708 | -52 |
| 2008-09-03 | vs SFN | 141 | L 2-9 | 66-75 | 3 | 23,481 | Aaron Cook | Barry Zito | Barry Zito | Aaron Cook | | 658 | 717 | -59 |
| 2008-09-05 | vs HOU | 142 | W 5-3 | 67-75 | 3 | 26,163 | Ubaldo Jimenez | Brian Moehler | Ubaldo Jimenez | Brian Moehler | Brian Fuentes | 663 | 720 | -57 |
| 2008-09-06 | vs HOU | 143 | L 0-2 | 67-76 | 3 | 32,352 | Jeff Francis | Roy Oswalt | Roy Oswalt | Jeff Francis | | 663 | 722 | -59 |
| 2008-09-07 | vs HOU | 144 | L 5-7 | 67-77 | 3 | 30,509 | Jorge de la Rosa | Wandy Rodriguez | Doug Brocail | Taylor Buchholz | Jose Valverde | 668 | 729 | -61 |
| 2008-09-09 | @ ATL | 145 | L 4-5 | 67-78 | 3 | 21,821 | Aaron Cook | Jorge Campillo | Julian Tavarez | Taylor Buchholz | | 672 | 734 | -62 |
| 2008-09-10 | @ ATL | 146 | L 5-9 | 67-79 | 3 | 19,693 | Livan Hernandez | James Parr | Jeff Bennett | Luis Vizcaino | | 677 | 743 | -66 |
| 2008-09-11 | @ ATL | 147 | L 4-8 | 67-80 | 3 | 20,039 | Ubaldo Jimenez | Jair Jurrjens | Jair Jurrjens | Glendon Rusch | | 681 | 751 | -70 |
| 2008-09-12 | vs LAN | 148 | L 2-7 | 67-81 | 3 | 30,147 | Jeff Francis | Chad Billingsley | Chad Billingsley | Jeff Francis | | 683 | 758 | -75 |
| 2008-09-13 | vs LAN | 149 | L 1-5 | 67-82 | 4 | 40,291 | Jorge de la Rosa | Clayton Kershaw | Clayton Kershaw | Jorge de la Rosa | | 684 | 763 | -79 |
| 2008-09-14 | vs LAN | 150 | W 1-0 | 68-82 | 4 | 28,910 | Aaron Cook | Greg Maddux | Manuel Corpas | Hong-Chih Kuo | | 685 | 763 | -78 |
| 2008-09-15 | vs SDN | 151 | L 5-11 | 68-83 | 4 | 25,296 | Greg Reynolds | Wade LeBlanc | Wade LeBlanc | Greg Reynolds | | 690 | 774 | -84 |
| 2008-09-16 | vs SDN | 152 | W 10-3 | 69-83 | 3 | 25,507 | Ubaldo Jimenez | Shawn Estes | Ubaldo Jimenez | Shawn Estes | | 700 | 777 | -77 |
| 2008-09-17 | vs SDN | 153 | W 1-0 | 70-83 | 3 | 25,155 | Livan Hernandez | Josh Geer | Livan Hernandez | Josh Geer | Brian Fuentes | 701 | 777 | -76 |
| 2008-09-19 | vs ARI | 154 | W 3-2 | 71-83 | 3 | 43,137 | Jorge de la Rosa | Max Scherzer | Jorge de la Rosa | Max Scherzer | Brian Fuentes | 704 | 779 | -75 |
| 2008-09-20 | vs ARI | 155 | L 3-5 | 71-84 | 3 | 38,283 | Aaron Cook | Doug Davis | Tony Pena | Brian Fuentes | Chad Qualls | 707 | 784 | -77 |
| 2008-09-21 | vs ARI | 156 | L 4-13 | 71-85 | 3 | 32,915 | Greg Reynolds | Dan Haren | Dan Haren | Greg Reynolds | | 711 | 797 | -86 |
| 2008-09-23 | @ SFN | 157 | W 9-4 | 72-85 | 3 | 33,922 | Ubaldo Jimenez | Tim Lincecum | Ubaldo Jimenez | Tim Lincecum | | 720 | 801 | -81 |
| 2008-09-24 | @ SFN | 158 | W 15-6 | 73-85 | 3 | 31,942 | Livan Hernandez | Jonathan Sanchez | Livan Hernandez | Jonathan Sanchez | | 735 | 807 | -72 |
| 2008-09-25 | @ SFN | 159 | W 3-1 | 74-85 | 3 | 31,857 | Jorge de la Rosa | Barry Zito | Jorge de la Rosa | Barry Zito | Brian Fuentes | 738 | 808 | -70 |
| 2008-09-26 | @ ARI | 160 | L 4-6 | 74-86 | 3 | 34,590 | Jason Hirsh | Dan Haren | Juan Cruz | Jason Grilli | Chad Qualls | 742 | 814 | -72 |
| 2008-09-27 | @ ARI | 161 | L 4-6 | 74-87 | 3 | 33,234 | Glendon Rusch | Brandon Webb | Brandon Lyon | Manuel Corpas | Chad Qualls | 746 | 820 | -74 |
| 2008-09-28 | @ ARI | 162 | L 1-2 | 74-88 | 3 | 35,908 | Ubaldo Jimenez | Randy Johnson | Randy Johnson | Luis Vizcaino | | 747 | 822 | -75 |