| 2008-04-01 | vs TOR | 1 | W 3-2 | 1-0 | 1 | 55,112 | Chien-Ming Wang | Roy Halladay | Chien-Ming Wang | Roy Halladay | Mariano Rivera | 3 | 2 | 1 |
| 2008-04-02 | vs TOR | 2 | L 2-5 | 1-1 | 3 | 48,544 | Mike Mussina | A.J. Burnett | A.J. Burnett | Mike Mussina | Jeremy Accardo | 5 | 7 | -2 |
| 2008-04-03 | vs TOR | 3 | W 3-2 | 2-1 | 2 | 47,785 | Phil Hughes | Dustin McGowan | Joba Chamberlain | Brian Wolfe | Mariano Rivera | 8 | 9 | -1 |
| 2008-04-04 | vs TBA | 4 | L 4-13 | 2-2 | 4 | 49,255 | Ian Kennedy | Andy Sonnanstine | Andy Sonnanstine | Ian Kennedy | | 12 | 22 | -10 |
| 2008-04-05 | vs TBA | 5 | L 3-6 | 2-3 | 5 | 52,247 | Andy Pettitte | Edwin Jackson | Edwin Jackson | Andy Pettitte | Troy Percival | 15 | 28 | -13 |
| 2008-04-06 | vs TBA | 6 | W 2-0 | 3-3 | 4 | 51,279 | Chien-Ming Wang | James Shields | Chien-Ming Wang | James Shields | Mariano Rivera | 17 | 28 | -11 |
| 2008-04-07 | vs TBA | 7 | W 6-1 | 4-3 | 3 | 41,302 | Mike Mussina | Jason Hammel | Mike Mussina | Jason Hammel | | 23 | 29 | -6 |
| 2008-04-08 | @ KCA | 8 | L 2-5 | 4-4 | 4 | 37,296 | Phil Hughes | Brian Bannister | Brian Bannister | Phil Hughes | Joakim Soria | 25 | 34 | -9 |
| 2008-04-09 | @ KCA | 9 | L 0-4 | 4-5 | 4 | 19,007 | Brian Bruney | Zack Greinke | Zack Greinke | Kyle Farnsworth | Jimmy Gobble | 25 | 38 | -13 |
| 2008-04-10 | @ KCA | 10 | W 6-1 | 5-5 | 3 | 16,143 | Andy Pettitte | John Bale | Andy Pettitte | John Bale | | 31 | 39 | -8 |
| 2008-04-11 | @ BOS | 11 | W 4-1 | 6-5 | 2 | 37,624 | Chien-Ming Wang | Clay Buchholz | Chien-Ming Wang | Mike Timlin | | 35 | 40 | -5 |
| 2008-04-12 | @ BOS | 12 | L 3-4 | 6-6 | 4 | 37,461 | Mike Mussina | Josh Beckett | Josh Beckett | Mike Mussina | Jonathan Papelbon | 38 | 44 | -6 |
| 2008-04-13 | @ BOS | 13 | L 5-8 | 6-7 | 5 | 37,876 | Phil Hughes | Daisuke Matsuzaka | Daisuke Matsuzaka | Phil Hughes | | 43 | 52 | -9 |
| 2008-04-14 | @ TBA | 14 | W 8-7 | 7-7 | 4 | 18,872 | Ian Kennedy | Andy Sonnanstine | Brian Bruney | Alberto Reyes | Mariano Rivera | 51 | 59 | -8 |
| 2008-04-15 | @ TBA | 15 | W 5-3 | 8-7 | 4 | 20,923 | Andy Pettitte | Edwin Jackson | Andy Pettitte | Edwin Jackson | Mariano Rivera | 56 | 62 | -6 |
| 2008-04-16 | vs BOS | 16 | W 15-9 | 9-7 | 2 | 54,667 | Chien-Ming Wang | Clay Buchholz | LaTroy Hawkins | Julian Tavarez | Brian Bruney | 71 | 71 | 0 |
| 2008-04-17 | vs BOS | 17 | L 5-7 | 9-8 | 3 | 55,088 | Mike Mussina | Josh Beckett | Josh Beckett | Mike Mussina | | 76 | 78 | -2 |
| 2008-04-18 | @ BAL | 18 | L 2-8 | 9-9 | 3 | 40,653 | Phil Hughes | Daniel Cabrera | Daniel Cabrera | Phil Hughes | | 78 | 86 | -8 |
| 2008-04-19 | @ BAL | 19 | L 0-6 | 9-10 | 4 | 41,776 | Ian Kennedy | Brian Burres | Brian Burres | Ian Kennedy | Jim Johnson | 78 | 92 | -14 |
| 2008-04-20 | @ BAL | 20 | W 7-1 | 10-10 | 4 | 37,501 | Andy Pettitte | Steve Trachsel | Andy Pettitte | Steve Trachsel | | 85 | 93 | -8 |
| 2008-04-22 | @ CHA | 21 | W 9-5 | 11-10 | 3 | 25,012 | Chien-Ming Wang | Jose Contreras | Chien-Ming Wang | Jose Contreras | | 94 | 98 | -4 |
| 2008-04-23 | @ CHA | 22 | W 6-4 | 12-10 | 3 | 27,751 | Mike Mussina | Javier Vazquez | Mike Mussina | Javier Vazquez | Mariano Rivera | 100 | 102 | -2 |
| 2008-04-24 | @ CHA | 23 | L 6-7 | 12-11 | 3 | 27,243 | Phil Hughes | Gavin Floyd | Bobby Jenks | Joba Chamberlain | | 106 | 109 | -3 |
| 2008-04-25 | @ CLE | 24 | L 4-6 | 12-12 | 4 | 31,467 | Andy Pettitte | Paul Byrd | Paul Byrd | Andy Pettitte | Rafael Betancourt | 110 | 115 | -5 |
| 2008-04-26 | @ CLE | 25 | L 3-4 | 12-13 | 4 | 35,765 | Ian Kennedy | Jeremy Sowers | Masahide Kobayashi | Ross Ohlendorf | | 113 | 119 | -6 |
| 2008-04-27 | @ CLE | 26 | W 1-0 | 13-13 | 4 | 31,598 | Chien-Ming Wang | CC Sabathia | Chien-Ming Wang | CC Sabathia | Mariano Rivera | 114 | 119 | -5 |
| 2008-04-28 | @ CLE | 27 | W 5-2 | 14-13 | 4 | 20,689 | Mike Mussina | Aaron Laffey | Mike Mussina | Aaron Laffey | Mariano Rivera | 119 | 121 | -2 |
| 2008-04-29 | vs DET | 28 | L 4-6 | 14-14 | 4 | 49,194 | Phil Hughes | Kenny Rogers | Kenny Rogers | Phil Hughes | Todd Jones | 123 | 127 | -4 |
| 2008-04-30 | vs DET | 29 | L 2-6 | 14-15 | 4 | 49,513 | Andy Pettitte | Jeremy Bonderman | Jeremy Bonderman | Andy Pettitte | | 125 | 133 | -8 |
| 2008-05-01 | vs DET | 30 | L 4-8 | 14-16 | 4 | 50,993 | Ian Kennedy | Nate Robertson | Nate Robertson | Jonathan Albaladejo | | 129 | 141 | -12 |
| 2008-05-02 | vs SEA | 31 | W 5-1 | 15-16 | 4 | 52,199 | Chien-Ming Wang | Erik Bedard | Chien-Ming Wang | Erik Bedard | | 134 | 142 | -8 |
| 2008-05-03 | vs SEA | 32 | W 6-1 | 16-16 | 4 | 52,810 | Mike Mussina | Felix Hernandez | Mike Mussina | Felix Hernandez | | 140 | 143 | -3 |
| 2008-05-04 | vs SEA | 33 | W 8-2 | 17-16 | 4 | 53,542 | Darrell Rasner | Carlos Silva | Darrell Rasner | Carlos Silva | | 148 | 145 | 3 |
| 2008-05-06 | vs CLE | 34 | L 3-5 | 17-17 | 4 | 50,713 | Andy Pettitte | Fausto Carmona | Rafael Perez | Joba Chamberlain | Rafael Betancourt | 151 | 150 | 1 |
| 2008-05-07 | vs CLE | 35 | L 0-3 | 17-18 | 4 | 50,199 | Chien-Ming Wang | Cliff Lee | Cliff Lee | Chien-Ming Wang | Rafael Betancourt | 151 | 153 | -2 |
| 2008-05-08 | vs CLE | 36 | W 6-3 | 18-18 | 4 | 53,227 | Mike Mussina | Paul Byrd | Mike Mussina | Paul Byrd | Mariano Rivera | 157 | 156 | 1 |
| 2008-05-09 | @ DET | 37 | L 5-6 | 18-19 | 4 | 44,062 | Kei Igawa | Kenny Rogers | Kenny Rogers | Kei Igawa | | 162 | 162 | 0 |
| 2008-05-10 | @ DET | 38 | W 5-2 | 19-19 | 4 | 44,580 | Darrell Rasner | Jeremy Bonderman | Darrell Rasner | Jeremy Bonderman | Mariano Rivera | 167 | 164 | 3 |
| 2008-05-12 | @ TBA | 39 | L 1-7 | 19-20 | 4 | 13,932 | Andy Pettitte | Matt Garza | Matt Garza | Andy Pettitte | | 168 | 171 | -3 |
| 2008-05-13 | @ TBA | 40 | L 1-2 | 19-21 | 4 | 16,558 | Chien-Ming Wang | Edwin Jackson | J.P. Howell | Mariano Rivera | | 169 | 173 | -4 |
| 2008-05-14 | @ TBA | 41 | W 2-1 | 20-21 | 4 | 20,936 | Mike Mussina | James Shields | Mike Mussina | James Shields | Mariano Rivera | 171 | 174 | -3 |
| 2008-05-15 | @ TBA | 42 | L 2-5 | 20-22 | 5 | 19,976 | Ian Kennedy | Scott Kazmir | Scott Kazmir | Ian Kennedy | Troy Percival | 173 | 179 | -6 |
| 2008-05-17 | vs NYN | 43 | L 4-7 | 20-23 | 5 | 55,093 | Andy Pettitte | Johan Santana | Johan Santana | Andy Pettitte | Billy Wagner | 177 | 186 | -9 |
| 2008-05-18 | vs NYN | 44 | L 2-11 | 20-24 | 5 | 55,012 | Chien-Ming Wang | Oliver Perez | Oliver Perez | Chien-Ming Wang | | 179 | 197 | -18 |
| 2008-05-20 | vs BAL | 45 | L 2-12 | 20-25 | 5 | 51,617 | Mike Mussina | Daniel Cabrera | Daniel Cabrera | Mike Mussina | | 181 | 209 | -28 |
| 2008-05-21 | vs BAL | 46 | W 8-0 | 21-25 | 5 | 50,682 | Darrell Rasner | Garrett Olson | Darrell Rasner | Garrett Olson | | 189 | 209 | -20 |
| 2008-05-22 | vs BAL | 47 | W 2-1 | 22-25 | 5 | 49,452 | Ian Kennedy | Brian Burres | Mariano Rivera | Jim Johnson | | 191 | 210 | -19 |
| 2008-05-23 | vs SEA | 48 | W 13-2 | 23-25 | 5 | 52,005 | Andy Pettitte | Erik Bedard | Andy Pettitte | Erik Bedard | | 204 | 212 | -8 |
| 2008-05-24 | vs SEA | 49 | W 12-6 | 24-25 | 5 | 53,512 | Mike Mussina | Carlos Silva | Mike Mussina | Carlos Silva | | 216 | 218 | -2 |
| 2008-05-25 | vs SEA | 50 | W 6-5 | 25-25 | 5 | 54,269 | Chien-Ming Wang | Jarrod Washburn | Edwar Ramirez | J.J. Putz | Mariano Rivera | 222 | 223 | -1 |
| 2008-05-26 | @ BAL | 51 | L 1-6 | 25-26 | 5 | 34,928 | Darrell Rasner | Garrett Olson | Garrett Olson | Darrell Rasner | | 223 | 229 | -6 |
| 2008-05-27 | @ BAL | 52 | L 9-10 | 25-27 | 5 | 24,030 | Ian Kennedy | Brian Burres | Matt Albers | LaTroy Hawkins | | 232 | 239 | -7 |
| 2008-05-28 | @ BAL | 53 | W 4-2 | 26-27 | 5 | 24,791 | Andy Pettitte | Jeremy Guthrie | Andy Pettitte | Jeremy Guthrie | Mariano Rivera | 236 | 241 | -5 |
| 2008-05-30 | @ MIN | 54 | W 6-5 | 27-27 | 5 | 30,188 | Mike Mussina | Glen Perkins | Mike Mussina | Glen Perkins | Mariano Rivera | 242 | 246 | -4 |
| 2008-05-31 | @ MIN | 55 | W 7-6 | 28-27 | 4 | 36,441 | Chien-Ming Wang | Boof Bonser | Ross Ohlendorf | Juan Rincon | Mariano Rivera | 249 | 252 | -3 |
| 2008-06-01 | @ MIN | 56 | L 1-5 | 28-28 | 4 | 27,479 | Darrell Rasner | Nick Blackburn | Brian Bass | Darrell Rasner | | 250 | 257 | -7 |
| 2008-06-02 | @ MIN | 57 | L 5-6 | 28-29 | 5 | 20,168 | Andy Pettitte | Livan Hernandez | Matt Guerrier | Kyle Farnsworth | Joe Nathan | 255 | 263 | -8 |
| 2008-06-03 | vs TOR | 58 | L 3-9 | 28-30 | 5 | 53,629 | Joba Chamberlain | Roy Halladay | Roy Halladay | Dan Giese | | 258 | 272 | -14 |
| 2008-06-04 | vs TOR | 59 | W 5-1 | 29-30 | 5 | 51,151 | Mike Mussina | Jesse Litsch | Mike Mussina | Jesse Litsch | | 263 | 273 | -10 |
| 2008-06-05 | vs TOR | 60 | W 9-8 | 30-30 | 5 | 53,571 | Chien-Ming Wang | Dustin McGowan | Kyle Farnsworth | B.J. Ryan | | 272 | 281 | -9 |
| 2008-06-06 | vs KCA | 61 | L 1-2 | 30-31 | 5 | 52,187 | Darrell Rasner | Kyle Davies | Kyle Davies | Darrell Rasner | Joakim Soria | 273 | 283 | -10 |
| 2008-06-07 | vs KCA | 62 | W 12-11 | 31-31 | 4 | 53,611 | Andy Pettitte | Brian Bannister | Mariano Rivera | Joakim Soria | | 285 | 294 | -9 |
| 2008-06-08 | vs KCA | 63 | W 6-3 | 32-31 | 4 | 54,213 | Joba Chamberlain | Zack Greinke | Dan Giese | Zack Greinke | Mariano Rivera | 291 | 297 | -6 |
| 2008-06-09 | vs KCA | 64 | L 2-3 | 32-32 | 4 | 53,633 | Mike Mussina | Luke Hochevar | Yasuhiko Yabuta | Mariano Rivera | Joakim Soria | 293 | 300 | -7 |
| 2008-06-10 | @ OAK | 65 | W 3-1 | 33-32 | 4 | 26,402 | Chien-Ming Wang | Dana Eveland | Chien-Ming Wang | Dana Eveland | Mariano Rivera | 296 | 301 | -5 |
| 2008-06-11 | @ OAK | 66 | L 4-8 | 33-33 | 4 | 27,292 | Darrell Rasner | Justin Duchscherer | Justin Duchscherer | Darrell Rasner | | 300 | 309 | -9 |
| 2008-06-12 | @ OAK | 67 | W 4-1 | 34-33 | 3 | 28,658 | Andy Pettitte | Joe Blanton | Andy Pettitte | Joe Blanton | Mariano Rivera | 304 | 310 | -6 |
| 2008-06-13 | @ HOU | 68 | W 2-1 | 35-33 | 3 | 43,095 | Joba Chamberlain | Shawn Chacon | Jose Veras | Doug Brocail | Kyle Farnsworth | 306 | 311 | -5 |
| 2008-06-14 | @ HOU | 69 | W 8-4 | 36-33 | 3 | 43,409 | Mike Mussina | Wandy Rodriguez | Mike Mussina | Wandy Rodriguez | | 314 | 315 | -1 |
| 2008-06-15 | @ HOU | 70 | W 13-0 | 37-33 | 3 | 43,165 | Chien-Ming Wang | Roy Oswalt | Chien-Ming Wang | Roy Oswalt | | 327 | 315 | 12 |
| 2008-06-17 | vs SDN | 71 | W 8-0 | 38-33 | 3 | 52,306 | Andy Pettitte | Randy Wolf | Andy Pettitte | Randy Wolf | | 335 | 315 | 20 |
| 2008-06-18 | vs SDN | 72 | W 8-5 | 39-33 | 3 | 52,628 | Darrell Rasner | Jake Peavy | Darrell Rasner | Jake Peavy | Mariano Rivera | 343 | 320 | 23 |
| 2008-06-19 | vs SDN | 73 | W 2-1 | 40-33 | 3 | 54,362 | Joba Chamberlain | Josh Banks | Jose Veras | Josh Banks | Mariano Rivera | 345 | 321 | 24 |
| 2008-06-20 | vs CIN | 74 | L 2-4 | 40-34 | 3 | 53,421 | Mike Mussina | Edinson Volquez | Edinson Volquez | Mike Mussina | Francisco Cordero | 347 | 325 | 22 |
| 2008-06-21 | vs CIN | 75 | L 0-6 | 40-35 | 3 | 54,509 | Dan Giese | Daryl Thompson | Bill Bray | Dan Giese | | 347 | 331 | 16 |
| 2008-06-22 | vs CIN | 76 | W 4-1 | 41-35 | 3 | 54,234 | Andy Pettitte | Johnny Cueto | Andy Pettitte | Johnny Cueto | Mariano Rivera | 351 | 332 | 19 |
| 2008-06-24 | @ PIT | 77 | L 5-12 | 41-36 | 3 | 38,867 | Darrell Rasner | Tom Gorzelanny | Tom Gorzelanny | Darrell Rasner | | 356 | 344 | 12 |
| 2008-06-25 | @ PIT | 78 | W 10-0 | 42-36 | 3 | 38,952 | Joba Chamberlain | Zach Duke | Joba Chamberlain | Zach Duke | | 366 | 344 | 22 |
| 2008-06-27 | @ NYN | 79 | W 9-0 | 43-37 | 3 | 56,308 | Sidney Ponson | Pedro Martinez | Sidney Ponson | Pedro Martinez | | 375 | 344 | 31 |
| 2008-06-27 | vs NYN | 80 | L 6-15 | 43-37 | 3 | 54,978 | Dan Giese | Mike Pelfrey | Mike Pelfrey | Dan Giese | | 381 | 359 | 22 |
| 2008-06-28 | @ NYN | 81 | W 3-2 | 44-37 | 3 | 56,172 | Andy Pettitte | Johan Santana | Andy Pettitte | Johan Santana | Mariano Rivera | 384 | 361 | 23 |
| 2008-06-29 | @ NYN | 82 | L 1-3 | 44-38 | 3 | 56,277 | Darrell Rasner | Oliver Perez | Oliver Perez | Darrell Rasner | Billy Wagner | 385 | 364 | 21 |
| 2008-06-30 | vs TEX | 83 | L 1-2 | 44-39 | 3 | 53,045 | Mike Mussina | Scott Feldman | Scott Feldman | Mike Mussina | C.J. Wilson | 386 | 366 | 20 |
| 2008-07-01 | vs TEX | 84 | L 2-3 | 44-40 | 3 | 53,223 | Joba Chamberlain | Kevin Millwood | Frank Francisco | Mariano Rivera | C.J. Wilson | 388 | 369 | 19 |
| 2008-07-02 | vs TEX | 85 | W 18-7 | 45-40 | 3 | 52,659 | Sidney Ponson | Luis Mendoza | Edwar Ramirez | Warner Madrigal | | 406 | 376 | 30 |
| 2008-07-03 | vs BOS | 86 | L 0-7 | 45-41 | 3 | 54,677 | Andy Pettitte | Jon Lester | Jon Lester | Andy Pettitte | | 406 | 383 | 23 |
| 2008-07-04 | vs BOS | 87 | L 4-6 | 45-42 | 4 | 55,130 | Darrell Rasner | Josh Beckett | Josh Beckett | Darrell Rasner | Jonathan Papelbon | 410 | 389 | 21 |
| 2008-07-05 | vs BOS | 88 | W 2-1 | 46-42 | 3 | 54,990 | Mike Mussina | Justin Masterson | Mike Mussina | Justin Masterson | Mariano Rivera | 412 | 390 | 22 |
| 2008-07-06 | vs BOS | 89 | W 5-4 | 47-42 | 3 | 54,922 | Joba Chamberlain | Tim Wakefield | Mariano Rivera | Jonathan Papelbon | | 417 | 394 | 23 |
| 2008-07-08 | vs TBA | 90 | W 5-0 | 48-42 | 3 | 53,089 | Andy Pettitte | Scott Kazmir | Andy Pettitte | Scott Kazmir | | 422 | 394 | 28 |
| 2008-07-09 | vs TBA | 91 | W 2-1 | 49-42 | 3 | 53,552 | Sidney Ponson | Edwin Jackson | Mariano Rivera | Grant Balfour | | 424 | 395 | 29 |
| 2008-07-10 | @ PIT | 92 | L 2-4 | 49-43 | 3 | 39,081 | Mike Mussina | Paul Maholm | Paul Maholm | Jose Veras | Damaso Marte | 426 | 399 | 27 |
| 2008-07-11 | @ TOR | 93 | L 0-5 | 49-44 | 3 | 43,078 | Joba Chamberlain | Roy Halladay | Roy Halladay | Joba Chamberlain | | 426 | 404 | 22 |
| 2008-07-12 | @ TOR | 94 | W 9-4 | 50-44 | 3 | 44,363 | Darrell Rasner | Jesse Litsch | Darrell Rasner | Jesse Litsch | | 435 | 408 | 27 |
| 2008-07-13 | @ TOR | 95 | L 1-4 | 50-45 | 3 | 43,854 | Andy Pettitte | A.J. Burnett | A.J. Burnett | Andy Pettitte | B.J. Ryan | 436 | 412 | 24 |
| 2008-07-18 | vs OAK | 96 | W 7-1 | 51-45 | 3 | 54,145 | Mike Mussina | Greg Smith | Mike Mussina | Greg Smith | | 443 | 413 | 30 |
| 2008-07-19 | vs OAK | 97 | W 4-3 | 52-45 | 3 | 54,183 | Joba Chamberlain | Sean Gallagher | David Robertson | Lenny DiNardo | | 447 | 416 | 31 |
| 2008-07-20 | vs OAK | 98 | W 2-1 | 53-45 | 3 | 54,366 | Andy Pettitte | Justin Duchscherer | Andy Pettitte | Justin Duchscherer | Mariano Rivera | 449 | 417 | 32 |
| 2008-07-21 | vs MIN | 99 | W 12-4 | 54-45 | 3 | 53,484 | Sidney Ponson | Nick Blackburn | Sidney Ponson | Nick Blackburn | | 461 | 421 | 40 |
| 2008-07-22 | vs MIN | 100 | W 8-2 | 55-45 | 3 | 53,406 | Darrell Rasner | Kevin Slowey | David Robertson | Kevin Slowey | | 469 | 423 | 46 |
| 2008-07-23 | vs MIN | 101 | W 5-1 | 56-45 | 3 | 54,114 | Mike Mussina | Glen Perkins | Mike Mussina | Glen Perkins | Mariano Rivera | 474 | 424 | 50 |
| 2008-07-25 | @ BOS | 102 | W 1-0 | 57-45 | 3 | 37,744 | Joba Chamberlain | Josh Beckett | Joba Chamberlain | Josh Beckett | Mariano Rivera | 475 | 424 | 51 |
| 2008-07-26 | @ BOS | 103 | W 10-3 | 58-45 | 3 | 37,225 | Andy Pettitte | Tim Wakefield | Andy Pettitte | Tim Wakefield | | 485 | 427 | 58 |
| 2008-07-27 | @ BOS | 104 | L 2-9 | 58-46 | 3 | 37,688 | Sidney Ponson | Jon Lester | Jon Lester | Sidney Ponson | | 487 | 436 | 51 |
| 2008-07-28 | vs BAL | 105 | L 4-13 | 58-47 | 3 | 54,120 | Mike Mussina | Jeremy Guthrie | Jeremy Guthrie | Mike Mussina | | 491 | 449 | 42 |
| 2008-07-29 | vs BAL | 106 | L 6-7 | 58-48 | 3 | 54,241 | Darrell Rasner | Daniel Cabrera | Daniel Cabrera | Darrell Rasner | | 497 | 456 | 41 |
| 2008-07-30 | vs BAL | 107 | W 13-3 | 59-48 | 3 | 54,296 | Joba Chamberlain | Dennis Sarfate | Joba Chamberlain | Dennis Sarfate | | 510 | 459 | 51 |
| 2008-07-31 | vs ANA | 108 | L 6-12 | 59-49 | 3 | 53,405 | Andy Pettitte | Jon Garland | Jon Garland | Andy Pettitte | | 516 | 471 | 45 |
| 2008-08-01 | vs ANA | 109 | L 0-1 | 59-50 | 3 | 53,997 | Sidney Ponson | Ervin Santana | Ervin Santana | Mariano Rivera | Francisco Rodriguez | 516 | 472 | 44 |
| 2008-08-02 | vs ANA | 110 | W 8-2 | 60-50 | 3 | 54,170 | Mike Mussina | Jered Weaver | Mike Mussina | Jered Weaver | | 524 | 474 | 50 |
| 2008-08-03 | vs ANA | 111 | W 14-9 | 61-50 | 3 | 54,204 | Darrell Rasner | John Lackey | Edwar Ramirez | Scot Shields | | 538 | 483 | 55 |
| 2008-08-04 | @ TEX | 112 | L 5-9 | 61-51 | 3 | 33,813 | Joba Chamberlain | Vicente Padilla | Eddie Guardado | Damaso Marte | | 543 | 492 | 51 |
| 2008-08-05 | @ TEX | 113 | L 6-8 | 61-52 | 3 | 34,473 | Andy Pettitte | Matt Harrison | Matt Harrison | Andy Pettitte | Eddie Guardado | 549 | 500 | 49 |
| 2008-08-06 | @ TEX | 114 | W 5-3 | 62-52 | 3 | 38,638 | Sidney Ponson | Tommy Hunter | Sidney Ponson | Tommy Hunter | Mariano Rivera | 554 | 503 | 51 |
| 2008-08-07 | @ TEX | 115 | W 3-0 | 63-52 | 3 | 44,603 | Mike Mussina | Scott Feldman | Mike Mussina | Scott Feldman | Mariano Rivera | 557 | 503 | 54 |
| 2008-08-08 | @ ANA | 116 | L 5-10 | 63-53 | 3 | 44,158 | Ian Kennedy | Jered Weaver | Jered Weaver | Ian Kennedy | | 562 | 513 | 49 |
| 2008-08-09 | @ ANA | 117 | L 4-11 | 63-54 | 3 | 43,919 | Dan Giese | John Lackey | Scot Shields | Edwar Ramirez | | 566 | 524 | 42 |
| 2008-08-10 | @ ANA | 118 | L 3-4 | 63-55 | 3 | 44,138 | Andy Pettitte | Joe Saunders | Francisco Rodriguez | Damaso Marte | | 569 | 528 | 41 |
| 2008-08-11 | @ MIN | 119 | L 0-4 | 63-56 | 3 | 30,126 | Sidney Ponson | Glen Perkins | Glen Perkins | Sidney Ponson | | 569 | 532 | 37 |
| 2008-08-12 | @ MIN | 120 | W 9-6 | 64-56 | 3 | 33,036 | Mike Mussina | Nick Blackburn | Jose Veras | Matt Guerrier | Edwar Ramirez | 578 | 538 | 40 |
| 2008-08-13 | @ MIN | 121 | L 2-4 | 64-57 | 3 | 35,187 | Darrell Rasner | Kevin Slowey | Kevin Slowey | Darrell Rasner | Joe Nathan | 580 | 542 | 38 |
| 2008-08-15 | vs KCA | 122 | L 3-4 | 64-58 | 3 | 53,067 | Andy Pettitte | Gil Meche | Leo Nunez | Mariano Rivera | Joakim Soria | 583 | 546 | 37 |
| 2008-08-16 | vs KCA | 123 | W 3-2 | 65-58 | 3 | 54,180 | Sidney Ponson | Zack Greinke | David Robertson | Jeff Fulchino | | 586 | 548 | 38 |
| 2008-08-17 | vs KCA | 124 | W 15-6 | 66-58 | 3 | 54,114 | Mike Mussina | Brian Bannister | Mike Mussina | Brian Bannister | | 601 | 554 | 47 |
| 2008-08-19 | @ TOR | 125 | L 1-2 | 66-59 | 3 | 37,221 | Darrell Rasner | A.J. Burnett | A.J. Burnett | Jose Veras | B.J. Ryan | 602 | 556 | 46 |
| 2008-08-20 | @ TOR | 126 | W 5-1 | 67-59 | 3 | 34,910 | Andy Pettitte | David Purcey | Andy Pettitte | David Purcey | | 607 | 557 | 50 |
| 2008-08-21 | @ TOR | 127 | L 3-14 | 67-60 | 3 | 37,037 | Sidney Ponson | Roy Halladay | Roy Halladay | Sidney Ponson | | 610 | 571 | 39 |
| 2008-08-22 | @ BAL | 128 | W 9-4 | 68-60 | 3 | 43,543 | Mike Mussina | Radhames Liz | Jose Veras | Jamie Walker | Mariano Rivera | 619 | 575 | 44 |
| 2008-08-23 | @ BAL | 129 | W 5-3 | 69-60 | 3 | 48,817 | Carl Pavano | Jeremy Guthrie | Carl Pavano | Jeremy Guthrie | Mariano Rivera | 624 | 578 | 46 |
| 2008-08-24 | @ BAL | 130 | W 8-7 | 70-60 | 3 | 42,746 | Darrell Rasner | Daniel Cabrera | Edwar Ramirez | Jamie Walker | Mariano Rivera | 632 | 585 | 47 |
| 2008-08-26 | vs BOS | 131 | L 3-7 | 70-61 | 3 | 55,058 | Andy Pettitte | Tim Wakefield | Tim Wakefield | Andy Pettitte | Jonathan Papelbon | 635 | 592 | 43 |
| 2008-08-27 | vs BOS | 132 | L 3-11 | 70-62 | 3 | 55,027 | Sidney Ponson | Paul Byrd | Paul Byrd | Sidney Ponson | | 638 | 603 | 35 |
| 2008-08-28 | vs BOS | 133 | W 3-2 | 71-62 | 3 | 55,092 | Mike Mussina | Jon Lester | Mariano Rivera | Justin Masterson | | 641 | 605 | 36 |
| 2008-08-29 | vs TOR | 134 | W 2-1 | 72-62 | 3 | 53,088 | Carl Pavano | A.J. Burnett | Carl Pavano | A.J. Burnett | Mariano Rivera | 643 | 606 | 37 |
| 2008-08-30 | vs TOR | 135 | L 6-7 | 72-63 | 3 | 53,273 | Darrell Rasner | John Parrish | Brandon League | Damaso Marte | B.J. Ryan | 649 | 613 | 36 |
| 2008-08-31 | vs TOR | 136 | L 2-6 | 72-64 | 3 | 53,634 | Andy Pettitte | Roy Halladay | Roy Halladay | Andy Pettitte | | 651 | 619 | 32 |
| 2008-09-01 | @ DET | 137 | W 13-9 | 73-64 | 3 | 44,336 | Sidney Ponson | Justin Verlander | Brian Bruney | Justin Verlander | | 664 | 628 | 36 |
| 2008-09-02 | @ TBA | 138 | W 7-2 | 74-64 | 3 | 21,629 | Mike Mussina | Matt Garza | Mike Mussina | Matt Garza | | 671 | 630 | 41 |
| 2008-09-03 | @ TBA | 139 | W 8-4 | 75-64 | 3 | 25,215 | Carl Pavano | Edwin Jackson | Edwar Ramirez | Edwin Jackson | | 679 | 634 | 45 |
| 2008-09-04 | @ TBA | 140 | L 5-7 | 75-65 | 3 | 26,080 | Darrell Rasner | Scott Kazmir | Scott Kazmir | Darrell Rasner | Dan Wheeler | 684 | 641 | 43 |
| 2008-09-05 | @ SEA | 141 | L 1-3 | 75-66 | 3 | 39,518 | Andy Pettitte | Brandon Morrow | Brandon Morrow | Andy Pettitte | J.J. Putz | 685 | 644 | 41 |
| 2008-09-06 | @ SEA | 142 | W 7-4 | 76-66 | 3 | 44,473 | Sidney Ponson | Ryan Rowland-Smith | Sidney Ponson | Sean Green | Mariano Rivera | 692 | 648 | 44 |
| 2008-09-07 | @ SEA | 143 | L 2-5 | 76-67 | 4 | 42,677 | Mike Mussina | Ryan Feierabend | Ryan Feierabend | Mike Mussina | J.J. Putz | 694 | 653 | 41 |
| 2008-09-08 | @ ANA | 144 | L 1-12 | 76-68 | 4 | 41,025 | Carl Pavano | Jon Garland | Jon Garland | Carl Pavano | | 695 | 665 | 30 |
| 2008-09-09 | @ ANA | 145 | W 7-1 | 77-68 | 4 | 43,042 | Alfredo Aceves | Ervin Santana | Alfredo Aceves | Ervin Santana | | 702 | 666 | 36 |
| 2008-09-10 | @ ANA | 146 | L 2-4 | 77-69 | 4 | 39,783 | Andy Pettitte | Dustin Moseley | Dustin Moseley | Andy Pettitte | Francisco Rodriguez | 704 | 670 | 34 |
| 2008-09-13 | vs TBA | 147 | L 1-7 | 78-70 | 4 | 54,088 | Mike Mussina | James Shields | James Shields | Mike Mussina | | 705 | 677 | 28 |
| 2008-09-13 | vs TBA | 148 | W 6-5 | 78-70 | 4 | 53,568 | Sidney Ponson | Matt Garza | Damaso Marte | J.P. Howell | Mariano Rivera | 711 | 682 | 29 |
| 2008-09-14 | vs TBA | 149 | W 8-4 | 79-70 | 4 | 54,279 | Carl Pavano | Edwin Jackson | Carl Pavano | Edwin Jackson | Mariano Rivera | 719 | 686 | 33 |
| 2008-09-15 | vs CHA | 150 | W 4-2 | 80-70 | 3 | 53,236 | Alfredo Aceves | Mark Buehrle | Phil Coke | Ehren Wassermann | Mariano Rivera | 723 | 688 | 35 |
| 2008-09-16 | vs CHA | 151 | L 2-6 | 80-71 | 3 | 52,558 | Andy Pettitte | Gavin Floyd | Gavin Floyd | Andy Pettitte | | 725 | 694 | 31 |
| 2008-09-17 | vs CHA | 152 | W 5-1 | 81-71 | 3 | 52,671 | Phil Hughes | Clayton Richard | Brian Bruney | Clayton Richard | | 730 | 695 | 35 |
| 2008-09-18 | vs CHA | 153 | W 9-2 | 82-71 | 3 | 53,152 | Mike Mussina | Javier Vazquez | Mike Mussina | Javier Vazquez | | 739 | 697 | 42 |
| 2008-09-19 | vs BAL | 154 | W 3-2 | 83-71 | 3 | 54,136 | Carl Pavano | Radhames Liz | Carl Pavano | Radhames Liz | Mariano Rivera | 742 | 699 | 43 |
| 2008-09-20 | vs BAL | 155 | W 1-0 | 84-71 | 3 | 54,662 | Alfredo Aceves | Brian Burres | Mariano Rivera | Jim Miller | | 743 | 699 | 44 |
| 2008-09-21 | vs BAL | 156 | W 7-3 | 85-71 | 3 | 54,610 | Andy Pettitte | Chris Waters | Andy Pettitte | Chris Waters | | 750 | 702 | 48 |
| 2008-09-23 | @ TOR | 157 | W 3-1 | 86-71 | 3 | 27,216 | Mike Mussina | Jesse Litsch | Mike Mussina | Jesse Litsch | Mariano Rivera | 753 | 703 | 50 |
| 2008-09-24 | @ TOR | 158 | W 6-2 | 87-71 | 3 | 28,701 | Phil Hughes | A.J. Burnett | Jose Veras | Jesse Carlson | | 759 | 705 | 54 |
| 2008-09-25 | @ TOR | 159 | L 2-8 | 87-72 | 3 | 44,346 | Carl Pavano | Roy Halladay | Roy Halladay | Carl Pavano | | 761 | 713 | 48 |
| 2008-09-26 | @ BOS | 160 | W 19-8 | 88-72 | 3 | 37,301 | Alfredo Aceves | David Pauley | David Robertson | David Pauley | | 780 | 721 | 59 |
| 2008-09-28 | @ BOS | 161 | W 6-2 | 89-73 | 3 | 37,091 | Mike Mussina | Daisuke Matsuzaka | Mike Mussina | Daisuke Matsuzaka | Mariano Rivera | 786 | 723 | 63 |
| 2008-09-28 | @ BOS | 162 | L 3-4 | 89-73 | 3 | 37,440 | Sidney Ponson | Tim Wakefield | Devern Hansack | Jose Veras | | 789 | 727 | 62 |