| 2008-03-31 | vs HOU | 1 | W 4-0 | 1-0 | 3 | 44,965 | Jake Peavy | Roy Oswalt | Jake Peavy | Roy Oswalt | | 4 | 0 | 4 |
| 2008-04-01 | vs HOU | 2 | W 2-1 | 2-0 | 4 | 20,825 | Chris Young | Brandon Backe | Chris Young | Brandon Backe | Trevor Hoffman | 6 | 1 | 5 |
| 2008-04-02 | vs HOU | 3 | L 6-9 | 2-1 | 2 | 18,714 | Greg Maddux | Wandy Rodriguez | Jose Valverde | Trevor Hoffman | | 12 | 10 | 2 |
| 2008-04-03 | vs HOU | 4 | W 3-2 | 3-1 | 1 | 24,432 | Randy Wolf | Shawn Chacon | Enrique Gonzalez | Oscar Villarreal | Trevor Hoffman | 15 | 12 | 3 |
| 2008-04-04 | vs LAN | 5 | L 1-7 | 3-2 | 2 | 42,474 | Justin Germano | Hiroki Kuroda | Hiroki Kuroda | Joe Thatcher | | 16 | 19 | -3 |
| 2008-04-05 | vs LAN | 6 | W 4-1 | 4-2 | 1 | 38,819 | Jake Peavy | Brad Penny | Jake Peavy | Brad Penny | | 20 | 20 | 0 |
| 2008-04-06 | vs LAN | 7 | L 2-3 | 4-3 | 3 | 44,165 | Chris Young | Derek Lowe | Jonathan Broxton | Trevor Hoffman | Takashi Saito | 22 | 23 | -1 |
| 2008-04-07 | @ SFN | 8 | W 8-4 | 5-3 | 2 | 42,861 | Greg Maddux | Matt Cain | Greg Maddux | Matt Cain | | 30 | 27 | 3 |
| 2008-04-08 | @ SFN | 9 | L 2-3 | 5-4 | 2 | 35,795 | Randy Wolf | Tim Lincecum | Brad Hennessey | Cla Meredith | | 32 | 30 | 2 |
| 2008-04-09 | @ SFN | 10 | L 0-1 | 5-5 | 2 | 30,310 | Justin Germano | Jonathan Sanchez | Tyler Walker | Heath Bell | | 32 | 31 | 1 |
| 2008-04-11 | @ LAN | 11 | W 7-5 | 6-5 | 2 | 54,052 | Jake Peavy | Brad Penny | Jake Peavy | Brad Penny | Trevor Hoffman | 39 | 36 | 3 |
| 2008-04-12 | @ LAN | 12 | L 1-11 | 6-6 | 2 | 54,955 | Chris Young | Derek Lowe | Derek Lowe | Chris Young | | 40 | 47 | -7 |
| 2008-04-13 | @ LAN | 13 | W 1-0 | 7-6 | 2 | 47,357 | Greg Maddux | Chad Billingsley | Greg Maddux | Chad Billingsley | Trevor Hoffman | 41 | 47 | -6 |
| 2008-04-15 | vs COL | 14 | W 6-0 | 8-6 | 2 | 24,439 | Randy Wolf | Ubaldo Jimenez | Randy Wolf | Ubaldo Jimenez | | 47 | 47 | 0 |
| 2008-04-16 | vs COL | 15 | L 2-10 | 8-7 | 2 | 21,730 | Justin Germano | Mark Redman | Mark Redman | Justin Germano | | 49 | 57 | -8 |
| 2008-04-17 | vs COL | 16 | L 1-2 | 8-8 | 2 | 25,984 | Jake Peavy | Jeff Francis | Kip Wells | Glendon Rusch | | 50 | 59 | -9 |
| 2008-04-18 | @ ARI | 17 | L 0-9 | 8-9 | 3 | 26,783 | Greg Maddux | Dan Haren | Dan Haren | Greg Maddux | | 50 | 68 | -18 |
| 2008-04-19 | @ ARI | 18 | L 3-10 | 8-10 | 3 | 39,726 | Chris Young | Edgar Gonzalez | Juan Cruz | Joe Thatcher | | 53 | 78 | -25 |
| 2008-04-20 | @ ARI | 19 | W 9-4 | 9-10 | 3 | 28,090 | Randy Wolf | Randy Johnson | Randy Wolf | Randy Johnson | | 62 | 82 | -20 |
| 2008-04-21 | @ HOU | 20 | L 3-10 | 9-11 | 3 | 28,600 | Justin Germano | Roy Oswalt | Roy Oswalt | Justin Germano | | 65 | 92 | -27 |
| 2008-04-22 | @ HOU | 21 | L 7-11 | 9-12 | 3 | 33,434 | Jake Peavy | Brandon Backe | Jose Valverde | Heath Bell | | 72 | 103 | -31 |
| 2008-04-23 | vs SFN | 22 | L 2-3 | 9-13 | 4 | 25,506 | Greg Maddux | Matt Cain | Keiichi Yabu | Glendon Rusch | Brian Wilson | 74 | 106 | -32 |
| 2008-04-24 | vs SFN | 23 | L 0-1 | 9-14 | 5 | 26,789 | Chris Young | Tim Lincecum | Tim Lincecum | Chris Young | Brian Wilson | 74 | 107 | -33 |
| 2008-04-25 | vs ARI | 24 | L 1-5 | 9-15 | 5 | 31,340 | Randy Wolf | Randy Johnson | Randy Johnson | Randy Wolf | | 75 | 112 | -37 |
| 2008-04-26 | vs ARI | 25 | W 8-7 | 10-15 | 5 | 31,295 | Justin Germano | Micah Owings | Glendon Rusch | Yusmeiro Petit | | 83 | 119 | -36 |
| 2008-04-27 | vs ARI | 26 | L 1-2 | 10-16 | 5 | 40,074 | Jake Peavy | Brandon Webb | Brandon Webb | Jake Peavy | Brandon Lyon | 84 | 121 | -37 |
| 2008-04-29 | @ PHI | 27 | L 4-7 | 10-17 | 5 | 34,207 | Greg Maddux | Cole Hamels | Cole Hamels | Greg Maddux | | 88 | 128 | -40 |
| 2008-04-30 | @ PHI | 28 | W 4-2 | 11-17 | 5 | 36,648 | Chris Young | Jamie Moyer | Chris Young | Jamie Moyer | Trevor Hoffman | 92 | 130 | -38 |
| 2008-05-01 | @ PHI | 29 | L 2-3 | 11-18 | 5 | 33,001 | Randy Wolf | Adam Eaton | Tom Gordon | Joe Thatcher | Brad Lidge | 94 | 133 | -39 |
| 2008-05-02 | @ FLO | 30 | L 4-6 | 11-19 | 5 | 14,562 | Justin Germano | Mark Hendrickson | Mark Hendrickson | Justin Germano | Kevin Gregg | 98 | 139 | -41 |
| 2008-05-03 | @ FLO | 31 | W 7-2 | 12-19 | 4 | 37,689 | Jake Peavy | Ricky Nolasco | Jake Peavy | Ricky Nolasco | | 105 | 141 | -36 |
| 2008-05-04 | @ FLO | 32 | L 3-10 | 12-20 | 5 | 11,422 | Greg Maddux | Andrew Miller | Andrew Miller | Greg Maddux | | 108 | 151 | -43 |
| 2008-05-06 | @ ATL | 33 | L 3-5 | 12-21 | 5 | 21,657 | Chris Young | Jair Jurrjens | Jair Jurrjens | Chris Young | Jeff Bennett | 111 | 156 | -45 |
| 2008-05-07 | @ ATL | 34 | L 2-5 | 12-22 | 5 | 25,194 | Randy Wolf | Tim Hudson | Tim Hudson | Randy Wolf | | 113 | 161 | -48 |
| 2008-05-08 | @ ATL | 35 | L 4-5 | 12-23 | 5 | 28,337 | Wil Ledezma | Jo-Jo Reyes | Manny Acosta | Joe Thatcher | | 117 | 166 | -49 |
| 2008-05-09 | vs COL | 36 | L 2-4 | 12-24 | 5 | 31,057 | Jake Peavy | Aaron Cook | Aaron Cook | Jake Peavy | Brian Fuentes | 119 | 170 | -51 |
| 2008-05-10 | vs COL | 37 | W 3-2 | 13-24 | 5 | 34,117 | Greg Maddux | Ubaldo Jimenez | Greg Maddux | Ubaldo Jimenez | Trevor Hoffman | 122 | 172 | -50 |
| 2008-05-11 | vs COL | 38 | W 6-1 | 14-24 | 5 | 28,624 | Chris Young | Greg Reynolds | Chris Young | Greg Reynolds | | 128 | 173 | -45 |
| 2008-05-12 | @ CHN | 39 | L 3-12 | 14-25 | 5 | 39,528 | Randy Wolf | Carlos Zambrano | Carlos Zambrano | Randy Wolf | | 131 | 185 | -54 |
| 2008-05-13 | @ CHN | 40 | W 4-3 | 15-25 | 5 | 40,028 | Shawn Estes | Jason Marquis | Shawn Estes | Jason Marquis | Trevor Hoffman | 135 | 188 | -53 |
| 2008-05-14 | @ CHN | 41 | L 5-8 | 15-26 | 5 | 39,650 | Jake Peavy | Ted Lilly | Ted Lilly | Jake Peavy | | 140 | 196 | -56 |
| 2008-05-15 | @ CHN | 42 | L 0-4 | 15-27 | 5 | 40,629 | Greg Maddux | Ryan Dempster | Ryan Dempster | Greg Maddux | Kerry Wood | 140 | 200 | -60 |
| 2008-05-16 | @ SEA | 43 | W 6-4 | 16-27 | 4 | 35,586 | Chris Young | Miguel Batista | Chris Young | Miguel Batista | Trevor Hoffman | 146 | 204 | -58 |
| 2008-05-17 | @ SEA | 44 | L 2-4 | 16-28 | 5 | 32,290 | Randy Wolf | Erik Bedard | Erik Bedard | Randy Wolf | J.J. Putz | 148 | 208 | -60 |
| 2008-05-18 | @ SEA | 45 | L 2-3 | 16-29 | 5 | 35,483 | Shawn Estes | Felix Hernandez | Arthur Rhodes | Heath Bell | J.J. Putz | 150 | 211 | -61 |
| 2008-05-19 | vs SLN | 46 | L 2-8 | 16-30 | 5 | 22,638 | Wil Ledezma | Todd Wellemeyer | Todd Wellemeyer | Wil Ledezma | | 152 | 219 | -67 |
| 2008-05-20 | vs SLN | 47 | W 3-2 | 17-30 | 5 | 27,181 | Greg Maddux | Joel Pineiro | Bryan Corey | Joel Pineiro | Trevor Hoffman | 155 | 221 | -66 |
| 2008-05-21 | vs SLN | 48 | L 3-11 | 17-31 | 5 | 21,011 | Chris Young | Braden Looper | Braden Looper | Chris Young | | 158 | 232 | -74 |
| 2008-05-22 | vs CIN | 49 | W 8-2 | 18-31 | 5 | 22,047 | Randy Wolf | Aaron Harang | Randy Wolf | Aaron Harang | | 166 | 234 | -68 |
| 2008-05-23 | vs CIN | 50 | L 2-3 | 18-32 | 5 | 26,422 | Shawn Estes | Edinson Volquez | David Weathers | Trevor Hoffman | Francisco Cordero | 168 | 237 | -69 |
| 2008-05-24 | vs CIN | 51 | L 2-7 | 18-33 | 5 | 27,499 | Wil Ledezma | Bronson Arroyo | Bronson Arroyo | Wil Ledezma | | 170 | 244 | -74 |
| 2008-05-25 | vs CIN | 52 | W 12-9 | 19-33 | 5 | 36,508 | Greg Maddux | Matt Belisle | Josh Banks | Edinson Volquez | | 182 | 253 | -71 |
| 2008-05-27 | vs WAS | 53 | W 4-2 | 20-33 | 5 | 18,774 | Randy Wolf | Shawn Hill | Heath Bell | Charlie Manning | Trevor Hoffman | 186 | 255 | -69 |
| 2008-05-28 | vs WAS | 54 | L 4-6 | 20-34 | 5 | 19,201 | Shawn Estes | Odalis Perez | Odalis Perez | Shawn Estes | Jon Rauch | 190 | 261 | -71 |
| 2008-05-29 | vs WAS | 55 | W 5-2 | 21-34 | 4 | 25,021 | Wil Ledezma | John Lannan | Heath Bell | Saul Rivera | Trevor Hoffman | 195 | 263 | -68 |
| 2008-05-30 | @ SFN | 56 | W 7-3 | 22-34 | 4 | 37,178 | Greg Maddux | Matt Cain | Cha-Seung Baek | Billy Sadler | | 202 | 266 | -64 |
| 2008-05-31 | @ SFN | 57 | W 5-1 | 23-34 | 4 | 34,921 | Josh Banks | Pat Misch | Josh Banks | Pat Misch | | 207 | 267 | -60 |
| 2008-06-01 | @ SFN | 58 | L 3-4 | 23-35 | 4 | 33,867 | Randy Wolf | Tim Lincecum | Alex Hinshaw | Trevor Hoffman | | 210 | 271 | -61 |
| 2008-06-02 | vs CHN | 59 | L 6-7 | 23-36 | 4 | 30,259 | Cha-Seung Baek | Carlos Zambrano | Carlos Zambrano | Cha-Seung Baek | Kerry Wood | 216 | 278 | -62 |
| 2008-06-03 | vs CHN | 60 | L 6-9 | 23-37 | 4 | 24,477 | Wil Ledezma | Jason Marquis | Jason Marquis | Bryan Corey | Kerry Wood | 222 | 287 | -65 |
| 2008-06-04 | vs CHN | 61 | W 2-1 | 24-37 | 4 | 25,258 | Greg Maddux | Ted Lilly | Heath Bell | Ted Lilly | Trevor Hoffman | 224 | 288 | -64 |
| 2008-06-05 | vs NYN | 62 | W 2-1 | 25-37 | 4 | 28,867 | Josh Banks | Mike Pelfrey | Trevor Hoffman | Scott Schoeneweis | | 226 | 289 | -63 |
| 2008-06-06 | vs NYN | 63 | W 2-1 | 26-37 | 4 | 27,749 | Randy Wolf | Johan Santana | Randy Wolf | Johan Santana | Trevor Hoffman | 228 | 290 | -62 |
| 2008-06-07 | vs NYN | 64 | W 2-1 | 27-37 | 4 | 38,972 | Cha-Seung Baek | Oliver Perez | Mike Adams | Pedro Feliciano | | 230 | 291 | -61 |
| 2008-06-08 | vs NYN | 65 | W 8-6 | 28-37 | 4 | 31,992 | Wil Ledezma | Pedro Martinez | Carlos Guevara | Billy Wagner | Trevor Hoffman | 238 | 297 | -59 |
| 2008-06-10 | vs LAN | 66 | L 2-7 | 28-38 | 4 | 26,860 | Greg Maddux | Clayton Kershaw | Scott Proctor | Justin Hampson | | 240 | 304 | -64 |
| 2008-06-11 | vs LAN | 67 | W 4-1 | 29-38 | 4 | 29,218 | Randy Wolf | Chad Billingsley | Randy Wolf | Chad Billingsley | Trevor Hoffman | 244 | 305 | -61 |
| 2008-06-12 | vs LAN | 68 | W 9-0 | 30-38 | 4 | 39,354 | Jake Peavy | Hiroki Kuroda | Jake Peavy | Hiroki Kuroda | | 253 | 305 | -52 |
| 2008-06-13 | @ CLE | 69 | L 5-9 | 30-39 | 4 | 31,399 | Josh Banks | Jeremy Sowers | Rafael Betancourt | Cla Meredith | Masahide Kobayashi | 258 | 314 | -56 |
| 2008-06-14 | @ CLE | 70 | W 8-3 | 31-39 | 3 | 37,484 | Cha-Seung Baek | Cliff Lee | Heath Bell | Edward Mujica | | 266 | 317 | -51 |
| 2008-06-15 | @ CLE | 71 | L 3-7 | 31-40 | 3 | 33,017 | Greg Maddux | CC Sabathia | CC Sabathia | Greg Maddux | | 269 | 324 | -55 |
| 2008-06-17 | @ NYA | 72 | L 0-8 | 31-41 | 3 | 52,306 | Randy Wolf | Andy Pettitte | Andy Pettitte | Randy Wolf | | 269 | 332 | -63 |
| 2008-06-18 | @ NYA | 73 | L 5-8 | 31-42 | 3 | 52,628 | Jake Peavy | Darrell Rasner | Darrell Rasner | Jake Peavy | Mariano Rivera | 274 | 340 | -66 |
| 2008-06-19 | @ NYA | 74 | L 1-2 | 31-43 | 5 | 54,362 | Josh Banks | Joba Chamberlain | Jose Veras | Josh Banks | Mariano Rivera | 275 | 342 | -67 |
| 2008-06-20 | vs DET | 75 | W 6-2 | 32-43 | 4 | 40,683 | Greg Maddux | Eddie Bonine | Heath Bell | Fernando Rodney | | 281 | 344 | -63 |
| 2008-06-21 | vs DET | 76 | L 5-7 | 32-44 | 5 | 34,749 | Cha-Seung Baek | Nate Robertson | Nate Robertson | Cha-Seung Baek | Todd Jones | 286 | 351 | -65 |
| 2008-06-22 | vs DET | 77 | L 3-5 | 32-45 | 5 | 28,779 | Randy Wolf | Justin Verlander | Justin Verlander | Randy Wolf | Todd Jones | 289 | 356 | -67 |
| 2008-06-24 | vs MIN | 78 | L 1-3 | 32-46 | 5 | 36,948 | Jake Peavy | Kevin Slowey | Dennys Reyes | Trevor Hoffman | Joe Nathan | 290 | 359 | -69 |
| 2008-06-25 | vs MIN | 79 | L 3-9 | 32-47 | 5 | 22,324 | Greg Maddux | Glen Perkins | Glen Perkins | Greg Maddux | | 293 | 368 | -75 |
| 2008-06-26 | vs MIN | 80 | L 3-4 | 32-48 | 5 | 28,789 | Josh Banks | Scott Baker | Scott Baker | Josh Banks | Joe Nathan | 296 | 372 | -76 |
| 2008-06-27 | vs SEA | 81 | L 2-5 | 32-49 | 5 | 28,640 | Randy Wolf | Jarrod Washburn | Jarrod Washburn | Randy Wolf | Brandon Morrow | 298 | 377 | -79 |
| 2008-06-28 | vs SEA | 82 | L 2-4 | 32-50 | 5 | 36,396 | Cha-Seung Baek | Carlos Silva | Carlos Silva | Cha-Seung Baek | Brandon Morrow | 300 | 381 | -81 |
| 2008-06-29 | vs SEA | 83 | L 2-9 | 32-51 | 5 | 29,966 | Jake Peavy | Erik Bedard | Erik Bedard | Jake Peavy | | 302 | 390 | -88 |
| 2008-06-30 | @ COL | 84 | W 15-8 | 33-51 | 4 | 43,248 | Greg Maddux | Jorge de la Rosa | Heath Bell | Brian Fuentes | | 317 | 398 | -81 |
| 2008-07-01 | @ COL | 85 | L 0-4 | 33-52 | 5 | 26,221 | Josh Banks | Aaron Cook | Aaron Cook | Josh Banks | | 317 | 402 | -85 |
| 2008-07-02 | @ COL | 86 | L 1-8 | 33-53 | 5 | 28,377 | Randy Wolf | Ubaldo Jimenez | Ubaldo Jimenez | Randy Wolf | | 318 | 410 | -92 |
| 2008-07-04 | @ ARI | 87 | W 5-1 | 34-53 | 5 | 49,110 | Cha-Seung Baek | Dan Haren | Cha-Seung Baek | Dan Haren | | 323 | 411 | -88 |
| 2008-07-05 | @ ARI | 88 | W 4-2 | 35-53 | 5 | 40,976 | Jake Peavy | Doug Davis | Jake Peavy | Doug Davis | Trevor Hoffman | 327 | 413 | -86 |
| 2008-07-06 | @ ARI | 89 | L 2-3 | 35-54 | 5 | 28,246 | Josh Banks | Randy Johnson | Randy Johnson | Josh Banks | Brandon Lyon | 329 | 416 | -87 |
| 2008-07-07 | vs FLO | 90 | L 1-3 | 35-55 | 5 | 23,840 | Greg Maddux | Ricky Nolasco | Ricky Nolasco | Greg Maddux | Kevin Gregg | 330 | 419 | -89 |
| 2008-07-08 | vs FLO | 91 | W 10-1 | 36-55 | 5 | 24,762 | Randy Wolf | Andrew Miller | Randy Wolf | Andrew Miller | | 340 | 420 | -80 |
| 2008-07-09 | vs FLO | 92 | L 2-5 | 36-56 | 5 | 31,186 | Cha-Seung Baek | Scott Olsen | Scott Olsen | Cha-Seung Baek | Kevin Gregg | 342 | 425 | -83 |
| 2008-07-11 | vs ATL | 93 | W 4-0 | 37-56 | 5 | 40,232 | Jake Peavy | Jo-Jo Reyes | Jake Peavy | Jo-Jo Reyes | Trevor Hoffman | 346 | 425 | -79 |
| 2008-07-12 | vs ATL | 94 | L 1-4 | 37-57 | 5 | 42,438 | Greg Maddux | Charlie Morton | Charlie Morton | Greg Maddux | Mike Gonzalez | 347 | 429 | -82 |
| 2008-07-13 | vs ATL | 95 | L 3-12 | 37-58 | 5 | 31,347 | Randy Wolf | Jorge Campillo | Jorge Campillo | Randy Wolf | | 350 | 441 | -91 |
| 2008-07-17 | @ SLN | 96 | L 3-4 | 37-59 | 5 | 42,148 | Jake Peavy | Kyle Lohse | Kyle Lohse | Jake Peavy | Ryan Franklin | 353 | 445 | -92 |
| 2008-07-18 | @ SLN | 97 | L 7-11 | 37-60 | 5 | 44,398 | Greg Maddux | Braden Looper | Kyle McClellan | Heath Bell | | 360 | 456 | -96 |
| 2008-07-19 | @ SLN | 98 | L 5-6 | 37-61 | 5 | 45,399 | Randy Wolf | Todd Wellemeyer | Todd Wellemeyer | Randy Wolf | Ryan Franklin | 365 | 462 | -97 |
| 2008-07-20 | @ SLN | 99 | L 5-9 | 37-62 | 5 | 44,214 | Cha-Seung Baek | Jaime Garcia | Brad Thompson | Bryan Corey | | 370 | 471 | -101 |
| 2008-07-21 | @ CIN | 100 | W 6-4 | 38-62 | 5 | 18,177 | Josh Banks | Homer Bailey | Clay Hensley | Francisco Cordero | Trevor Hoffman | 376 | 475 | -99 |
| 2008-07-22 | @ CIN | 101 | L 3-4 | 38-63 | 5 | 21,233 | Jake Peavy | Johnny Cueto | Gary Majewski | Bryan Corey | | 379 | 479 | -100 |
| 2008-07-23 | @ CIN | 102 | L 5-9 | 38-64 | 5 | 22,970 | Greg Maddux | Bronson Arroyo | Bronson Arroyo | Cla Meredith | Francisco Cordero | 384 | 488 | -104 |
| 2008-07-24 | @ PIT | 103 | L 1-9 | 38-65 | 5 | 17,916 | Clay Hensley | Yoslan Herrera | Yoslan Herrera | Clay Hensley | | 385 | 497 | -112 |
| 2008-07-25 | @ PIT | 104 | W 6-5 | 39-65 | 5 | 25,727 | Cha-Seung Baek | Zach Duke | Cha-Seung Baek | Zach Duke | Trevor Hoffman | 391 | 502 | -111 |
| 2008-07-26 | @ PIT | 105 | W 9-6 | 40-65 | 5 | 27,794 | Josh Banks | John Van Benschoten | Josh Banks | John Van Benschoten | Trevor Hoffman | 400 | 508 | -108 |
| 2008-07-27 | @ PIT | 106 | W 3-1 | 41-65 | 5 | 21,721 | Jake Peavy | Paul Maholm | Jake Peavy | John Grabow | Trevor Hoffman | 403 | 509 | -106 |
| 2008-07-28 | vs ARI | 107 | W 8-5 | 42-65 | 5 | 29,302 | Greg Maddux | Micah Owings | Greg Maddux | Micah Owings | Trevor Hoffman | 411 | 514 | -103 |
| 2008-07-29 | vs ARI | 108 | L 0-3 | 42-66 | 5 | 29,131 | Chris Young | Doug Davis | Doug Davis | Clay Hensley | Brandon Lyon | 411 | 517 | -106 |
| 2008-07-30 | vs ARI | 109 | L 3-7 | 42-67 | 5 | 31,755 | Cha-Seung Baek | Dan Haren | Dan Haren | Cha-Seung Baek | | 414 | 524 | -110 |
| 2008-08-01 | vs SFN | 110 | L 2-3 | 42-68 | 5 | 33,926 | Josh Banks | Tim Lincecum | Sergio Romo | Trevor Hoffman | Brian Wilson | 416 | 527 | -111 |
| 2008-08-02 | vs SFN | 111 | L 0-2 | 42-69 | 5 | 41,688 | Jake Peavy | Barry Zito | Barry Zito | Jake Peavy | Brian Wilson | 416 | 529 | -113 |
| 2008-08-03 | vs SFN | 112 | W 4-1 | 43-69 | 5 | 33,060 | Greg Maddux | Kevin Correia | Greg Maddux | Kevin Correia | Trevor Hoffman | 420 | 530 | -110 |
| 2008-08-05 | @ NYN | 113 | L 5-6 | 43-70 | 5 | 52,130 | Chris Young | Mike Pelfrey | Mike Pelfrey | Mike Adams | Scott Schoeneweis | 425 | 536 | -111 |
| 2008-08-06 | @ NYN | 114 | W 4-2 | 44-70 | 5 | 48,018 | Cha-Seung Baek | Pedro Martinez | Cha-Seung Baek | Pedro Martinez | Trevor Hoffman | 429 | 538 | -109 |
| 2008-08-07 | @ NYN | 115 | L 3-5 | 44-71 | 5 | 49,352 | Josh Banks | Johan Santana | Aaron Heilman | Heath Bell | | 432 | 543 | -111 |
| 2008-08-08 | @ COL | 116 | L 3-6 | 44-72 | 5 | 33,147 | Jake Peavy | Glendon Rusch | Glendon Rusch | Jake Peavy | Brian Fuentes | 435 | 549 | -114 |
| 2008-08-09 | @ COL | 117 | W 8-3 | 45-72 | 5 | 41,640 | Greg Maddux | Aaron Cook | Greg Maddux | Aaron Cook | Trevor Hoffman | 443 | 552 | -109 |
| 2008-08-10 | @ COL | 118 | W 16-7 | 46-72 | 5 | 45,660 | Chris Young | Livan Hernandez | Justin Hampson | Livan Hernandez | | 459 | 559 | -100 |
| 2008-08-12 | vs MIL | 119 | L 2-5 | 46-73 | 5 | 28,373 | Cha-Seung Baek | Jeff Suppan | Jeff Suppan | Cha-Seung Baek | Salomon Torres | 461 | 564 | -103 |
| 2008-08-13 | vs MIL | 120 | L 1-7 | 46-74 | 5 | 32,771 | Josh Banks | CC Sabathia | CC Sabathia | Josh Banks | | 462 | 571 | -109 |
| 2008-08-14 | vs MIL | 121 | W 3-2 | 47-74 | 5 | 30,145 | Jake Peavy | Ben Sheets | Jake Peavy | Ben Sheets | Trevor Hoffman | 465 | 573 | -108 |
| 2008-08-15 | vs PHI | 122 | L 0-1 | 47-75 | 5 | 37,558 | Greg Maddux | Jamie Moyer | Jamie Moyer | Greg Maddux | Brad Lidge | 465 | 574 | -109 |
| 2008-08-16 | vs PHI | 123 | W 8-3 | 48-75 | 5 | 33,956 | Chad Reineke | Kyle Kendrick | Chad Reineke | Kyle Kendrick | | 473 | 577 | -104 |
| 2008-08-17 | vs PHI | 124 | L 1-2 | 48-76 | 5 | 34,756 | Cha-Seung Baek | Cole Hamels | Cole Hamels | Cha-Seung Baek | Brad Lidge | 474 | 579 | -105 |
| 2008-08-19 | @ ARI | 125 | L 6-7 | 48-77 | 5 | 24,739 | Josh Banks | Doug Davis | Doug Davis | Josh Banks | Tony Pena | 480 | 586 | -106 |
| 2008-08-20 | @ ARI | 126 | L 6-8 | 48-78 | 5 | 26,518 | Jake Peavy | Dan Haren | Dan Haren | Jake Peavy | Jon Rauch | 486 | 594 | -108 |
| 2008-08-21 | @ ARI | 127 | L 1-4 | 48-79 | 5 | 25,611 | Chad Reineke | Brandon Webb | Brandon Webb | Chad Reineke | | 487 | 598 | -111 |
| 2008-08-22 | @ SFN | 128 | L 0-5 | 48-80 | 5 | 33,615 | Cha-Seung Baek | Tim Lincecum | Tim Lincecum | Cha-Seung Baek | | 487 | 603 | -116 |
| 2008-08-23 | @ SFN | 129 | L 3-4 | 48-81 | 5 | 37,081 | Dirk Hayhurst | Barry Zito | Barry Zito | Mike Adams | Brian Wilson | 490 | 607 | -117 |
| 2008-08-24 | @ SFN | 130 | L 4-7 | 48-82 | 5 | 37,174 | Josh Banks | Kevin Correia | Kevin Correia | Mike Adams | Brian Wilson | 494 | 614 | -120 |
| 2008-08-25 | vs ARI | 131 | W 4-2 | 49-82 | 5 | 29,197 | Jake Peavy | Dan Haren | Trevor Hoffman | Jon Rauch | | 498 | 616 | -118 |
| 2008-08-26 | vs ARI | 132 | W 9-2 | 50-82 | 5 | 32,104 | Chad Reineke | Brandon Webb | Chad Reineke | Brandon Webb | | 507 | 618 | -111 |
| 2008-08-27 | vs ARI | 133 | W 5-4 | 51-82 | 5 | 24,563 | Cha-Seung Baek | Randy Johnson | Mike Adams | Chad Qualls | Trevor Hoffman | 512 | 622 | -110 |
| 2008-08-29 | vs COL | 134 | L 4-9 | 51-83 | 5 | 25,274 | Dirk Hayhurst | Aaron Cook | Aaron Cook | Dirk Hayhurst | | 516 | 631 | -115 |
| 2008-08-30 | vs COL | 135 | W 9-4 | 52-83 | 5 | 30,240 | Josh Geer | Ubaldo Jimenez | Josh Geer | Ubaldo Jimenez | | 525 | 635 | -110 |
| 2008-08-31 | vs COL | 136 | W 2-1 | 53-83 | 5 | 26,395 | Jake Peavy | Jeff Francis | Trevor Hoffman | Taylor Buchholz | | 527 | 636 | -109 |
| 2008-09-01 | @ LAN | 137 | L 2-5 | 53-84 | 5 | 44,087 | Chris Young | Greg Maddux | Greg Maddux | Chris Young | Jonathan Broxton | 529 | 641 | -112 |
| 2008-09-02 | @ LAN | 138 | L 4-8 | 53-85 | 5 | 39,330 | Cha-Seung Baek | Clayton Kershaw | Clayton Kershaw | Cha-Seung Baek | | 533 | 649 | -116 |
| 2008-09-03 | @ LAN | 139 | L 4-6 | 53-86 | 5 | 48,822 | Wade LeBlanc | Hiroki Kuroda | Hiroki Kuroda | Wade LeBlanc | Jonathan Broxton | 537 | 655 | -118 |
| 2008-09-04 | @ MIL | 140 | W 5-2 | 54-86 | 5 | 33,182 | Shawn Estes | Jeff Suppan | Shawn Estes | Jeff Suppan | Trevor Hoffman | 542 | 657 | -115 |
| 2008-09-05 | @ MIL | 141 | L 2-3 | 54-87 | 5 | 41,519 | Josh Geer | CC Sabathia | Brian Shouse | Brian Falkenborg | | 544 | 660 | -116 |
| 2008-09-06 | @ MIL | 142 | L 0-1 | 54-88 | 5 | 42,667 | Jake Peavy | Ben Sheets | Ben Sheets | Jake Peavy | | 544 | 661 | -117 |
| 2008-09-07 | @ MIL | 143 | W 10-1 | 55-88 | 5 | 44,568 | Chris Young | Manny Parra | Chris Young | Manny Parra | | 554 | 662 | -108 |
| 2008-09-08 | vs LAN | 144 | W 4-0 | 56-88 | 5 | 25,942 | Cha-Seung Baek | Greg Maddux | Cha-Seung Baek | Greg Maddux | | 558 | 662 | -104 |
| 2008-09-09 | vs LAN | 145 | L 2-6 | 56-89 | 5 | 26,614 | Wade LeBlanc | Hiroki Kuroda | Joe Beimel | Heath Bell | | 560 | 668 | -108 |
| 2008-09-10 | vs LAN | 146 | L 2-7 | 56-90 | 5 | 27,208 | Shawn Estes | Derek Lowe | Derek Lowe | Shawn Estes | | 562 | 675 | -113 |
| 2008-09-11 | vs SFN | 147 | W 11-3 | 57-90 | 5 | 30,497 | Josh Geer | Matt Cain | Josh Geer | Matt Cain | | 573 | 678 | -105 |
| 2008-09-12 | vs SFN | 148 | L 2-5 | 57-91 | 5 | 24,610 | Jake Peavy | Jonathan Sanchez | Jonathan Sanchez | Jake Peavy | Brian Wilson | 575 | 683 | -108 |
| 2008-09-13 | vs SFN | 149 | L 0-7 | 57-92 | 5 | 31,015 | Chris Young | Tim Lincecum | Tim Lincecum | Chris Young | | 575 | 690 | -115 |
| 2008-09-14 | vs SFN | 150 | L 6-8 | 57-93 | 5 | 25,476 | Cha-Seung Baek | Barry Zito | Sergio Romo | Dirk Hayhurst | Brian Wilson | 581 | 698 | -117 |
| 2008-09-15 | @ COL | 151 | W 11-5 | 58-93 | 5 | 25,296 | Wade LeBlanc | Greg Reynolds | Wade LeBlanc | Greg Reynolds | | 592 | 703 | -111 |
| 2008-09-16 | @ COL | 152 | L 3-10 | 58-94 | 5 | 25,507 | Shawn Estes | Ubaldo Jimenez | Ubaldo Jimenez | Shawn Estes | | 595 | 713 | -118 |
| 2008-09-17 | @ COL | 153 | L 0-1 | 58-95 | 5 | 25,155 | Josh Geer | Livan Hernandez | Livan Hernandez | Josh Geer | Brian Fuentes | 595 | 714 | -119 |
| 2008-09-19 | @ WAS | 154 | W 11-6 | 59-95 | 5 | 28,600 | Dirk Hayhurst | Collin Balester | Justin Hampson | Levale Speigner | | 606 | 720 | -114 |
| 2008-09-20 | @ WAS | 155 | W 6-1 | 60-95 | 5 | 27,474 | Chris Young | John Lannan | Chris Young | John Lannan | | 612 | 721 | -109 |
| 2008-09-21 | @ WAS | 156 | W 6-2 | 61-95 | 5 | 29,608 | Cha-Seung Baek | Odalis Perez | Cha-Seung Baek | Odalis Perez | | 618 | 723 | -105 |
| 2008-09-23 | @ LAN | 157 | L 1-10 | 61-96 | 5 | 48,905 | Wade LeBlanc | Chad Billingsley | Chad Billingsley | Wade LeBlanc | | 619 | 733 | -114 |
| 2008-09-24 | @ LAN | 158 | L 4-12 | 61-97 | 5 | 44,776 | Shawn Estes | Clayton Kershaw | Clayton Kershaw | Mike Ekstrom | | 623 | 745 | -122 |
| 2008-09-25 | @ LAN | 159 | W 7-5 | 62-97 | 5 | 52,569 | Jake Peavy | Eric Stults | Jake Peavy | Eric Stults | Trevor Hoffman | 630 | 750 | -120 |
| 2008-09-26 | vs PIT | 160 | L 3-6 | 62-98 | 5 | 27,227 | Josh Geer | Ian Snell | Ian Snell | Mike Ekstrom | Matt Capps | 633 | 756 | -123 |
| 2008-09-27 | vs PIT | 161 | W 3-2 | 63-98 | 5 | 29,825 | Chris Young | Jimmy Barthmaier | Chris Young | Jimmy Barthmaier | Trevor Hoffman | 636 | 758 | -122 |
| 2008-09-28 | vs PIT | 162 | L 1-6 | 63-99 | 5 | 29,191 | Cha-Seung Baek | Ross Ohlendorf | Tyler Yates | Wade LeBlanc | | 637 | 764 | -127 |