| 2006-04-02 | @ CHA | 1 | L 4-10 | 0-1 | 2 | 38,802 | CC Sabathia | Mark Buehrle | Brandon McCarthy | Fernando Cabrera | | 4 | 10 | -6 |
| 2006-04-04 | @ CHA | 2 | W 8-2 | 1-1 | 3 | 37,591 | Jake Westbrook | Freddy Garcia | Jake Westbrook | Freddy Garcia | | 12 | 12 | 0 |
| 2006-04-05 | @ CHA | 3 | W 4-3 | 2-1 | 2 | 33,586 | Cliff Lee | Jose Contreras | Danny Graves | Neal Cotts | Bob Wickman | 16 | 15 | 1 |
| 2006-04-07 | vs MIN | 4 | W 11-6 | 3-1 | 2 | 42,445 | Paul Byrd | Kyle Lohse | Paul Byrd | Kyle Lohse | | 27 | 21 | 6 |
| 2006-04-08 | vs MIN | 5 | W 3-0 | 4-1 | 2 | 25,107 | Jason Johnson | Scott Baker | Jason Johnson | Scott Baker | Bob Wickman | 30 | 21 | 9 |
| 2006-04-09 | vs MIN | 6 | W 3-2 | 5-1 | 1 | 23,311 | Jake Westbrook | Johan Santana | Jake Westbrook | Johan Santana | Bob Wickman | 33 | 23 | 10 |
| 2006-04-11 | vs SEA | 7 | W 9-5 | 6-1 | 1 | 17,559 | Cliff Lee | Jarrod Washburn | Cliff Lee | Jarrod Washburn | | 42 | 28 | 14 |
| 2006-04-12 | vs SEA | 8 | L 9-11 | 6-2 | 1 | 14,773 | Paul Byrd | Gil Meche | Jake Woods | Paul Byrd | Eddie Guardado | 51 | 39 | 12 |
| 2006-04-13 | vs SEA | 9 | L 5-9 | 6-3 | 1 | 24,638 | Jason Johnson | Felix Hernandez | Julio Mateo | Scott Sauerbeck | J.J. Putz | 56 | 48 | 8 |
| 2006-04-14 | @ DET | 10 | L 1-5 | 6-4 | 1 | 27,358 | Jake Westbrook | Kenny Rogers | Kenny Rogers | Jake Westbrook | | 57 | 53 | 4 |
| 2006-04-15 | @ DET | 11 | W 7-2 | 7-4 | 1 | 30,107 | Fausto Carmona | Jeremy Bonderman | Fausto Carmona | Jeremy Bonderman | | 64 | 55 | 9 |
| 2006-04-16 | @ DET | 12 | L 0-1 | 7-5 | 2 | 14,303 | Cliff Lee | Mike Maroth | Mike Maroth | Cliff Lee | Fernando Rodney | 64 | 56 | 8 |
| 2006-04-17 | @ DET | 13 | W 10-2 | 8-5 | 2 | 19,126 | Paul Byrd | Nate Robertson | Paul Byrd | Nate Robertson | | 74 | 58 | 16 |
| 2006-04-18 | @ BAL | 14 | W 15-1 | 9-5 | 2 | 17,354 | Jason Johnson | Bruce Chen | Jason Johnson | Bruce Chen | | 89 | 59 | 30 |
| 2006-04-19 | @ BAL | 15 | L 9-18 | 9-6 | 2 | 19,510 | Jake Westbrook | Rodrigo Lopez | John Halama | Jake Westbrook | | 98 | 77 | 21 |
| 2006-04-20 | @ BAL | 16 | L 4-9 | 9-7 | 2 | 22,031 | Fausto Carmona | Erik Bedard | Erik Bedard | Fausto Carmona | | 102 | 86 | 16 |
| 2006-04-21 | @ KCA | 17 | W 6-5 | 10-7 | 2 | 16,791 | Cliff Lee | Mark Redman | Danny Graves | Elmer Dessens | Bob Wickman | 108 | 91 | 17 |
| 2006-04-22 | @ KCA | 18 | L 5-11 | 10-8 | 3 | 19,645 | Paul Byrd | Joe Mays | Mike Wood | Paul Byrd | | 113 | 102 | 11 |
| 2006-04-23 | @ KCA | 19 | L 1-5 | 10-9 | 3 | 12,194 | Jason Johnson | Jeremy Affeldt | Jeremy Affeldt | Jason Johnson | | 114 | 107 | 7 |
| 2006-04-25 | vs BOS | 20 | L 6-8 | 10-10 | 3 | 18,438 | Jake Westbrook | Curt Schilling | Keith Foulke | Guillermo Mota | Jonathan Papelbon | 120 | 115 | 5 |
| 2006-04-26 | vs BOS | 21 | W 7-1 | 11-10 | 3 | 21,575 | Cliff Lee | Tim Wakefield | Cliff Lee | Tim Wakefield | | 127 | 116 | 11 |
| 2006-04-27 | vs BOS | 22 | W 15-3 | 12-10 | 3 | 26,952 | Paul Byrd | Josh Beckett | Paul Byrd | Josh Beckett | | 142 | 119 | 23 |
| 2006-04-28 | vs TEX | 23 | W 7-6 | 13-10 | 3 | 22,106 | Jason Johnson | John Koronka | Jason Davis | Rick Bauer | Bob Wickman | 149 | 125 | 24 |
| 2006-04-29 | vs TEX | 24 | L 5-7 | 13-11 | 3 | 37,496 | Fausto Carmona | Kevin Millwood | Kevin Millwood | Fausto Carmona | Akinori Otsuka | 154 | 132 | 22 |
| 2006-04-30 | vs TEX | 25 | L 4-8 | 13-12 | 3 | 22,989 | Jake Westbrook | Vicente Padilla | Vicente Padilla | Jason Davis | | 158 | 140 | 18 |
| 2006-05-01 | vs CHA | 26 | L 6-8 | 13-13 | 3 | 17,845 | Cliff Lee | Javier Vazquez | Javier Vazquez | Cliff Lee | Bobby Jenks | 164 | 148 | 16 |
| 2006-05-02 | vs CHA | 27 | W 7-1 | 14-13 | 3 | 22,630 | CC Sabathia | Mark Buehrle | CC Sabathia | Mark Buehrle | | 171 | 149 | 22 |
| 2006-05-03 | @ OAK | 28 | W 14-3 | 15-13 | 3 | 18,248 | Paul Byrd | Dan Haren | Paul Byrd | Dan Haren | | 185 | 152 | 33 |
| 2006-05-04 | @ OAK | 29 | L 4-12 | 15-14 | 3 | 14,695 | Jason Johnson | Kirk Saarloos | Kirk Saarloos | Jason Johnson | Chad Gaudin | 189 | 164 | 25 |
| 2006-05-05 | @ SEA | 30 | W 9-4 | 16-14 | 3 | 32,998 | Jake Westbrook | Jamie Moyer | Jake Westbrook | Rafael Soriano | | 198 | 168 | 30 |
| 2006-05-06 | @ SEA | 31 | L 1-4 | 16-15 | 3 | 28,672 | Cliff Lee | Joel Pineiro | Joel Pineiro | Cliff Lee | J.J. Putz | 199 | 172 | 27 |
| 2006-05-07 | @ SEA | 32 | W 2-0 | 17-15 | 3 | 35,562 | CC Sabathia | Jarrod Washburn | CC Sabathia | Jarrod Washburn | Bob Wickman | 201 | 172 | 29 |
| 2006-05-08 | @ KCA | 33 | L 3-4 | 17-16 | 3 | 9,029 | Paul Byrd | Denny Bautista | Mike Wood | Paul Byrd | Ambiorix Burgos | 204 | 176 | 28 |
| 2006-05-09 | @ KCA | 34 | L 7-10 | 17-17 | 3 | 14,784 | Jason Johnson | Jeremy Affeldt | Joel Peralta | Danny Graves | | 211 | 186 | 25 |
| 2006-05-10 | @ KCA | 35 | L 8-10 | 17-18 | 3 | 24,471 | Jake Westbrook | Scott Elarton | Ambiorix Burgos | Guillermo Mota | | 219 | 196 | 23 |
| 2006-05-12 | vs DET | 36 | L 4-5 | 17-19 | 3 | 23,588 | Cliff Lee | Kenny Rogers | Kenny Rogers | Cliff Lee | Todd Jones | 223 | 201 | 22 |
| 2006-05-13 | vs DET | 37 | L 0-3 | 17-20 | 4 | 24,051 | CC Sabathia | Jeremy Bonderman | Jeremy Bonderman | CC Sabathia | Todd Jones | 223 | 204 | 19 |
| 2006-05-14 | vs DET | 38 | L 2-3 | 17-21 | 4 | 21,875 | Jason Johnson | Mike Maroth | Mike Maroth | Jason Johnson | Fernando Rodney | 225 | 207 | 18 |
| 2006-05-16 | vs KCA | 39 | W 6-4 | 18-21 | 3 | 15,399 | Paul Byrd | Scott Elarton | Jason Davis | Ambiorix Burgos | | 231 | 211 | 20 |
| 2006-05-17 | vs KCA | 40 | W 5-0 | 19-21 | 3 | 15,064 | Jake Westbrook | Jeremy Affeldt | Jake Westbrook | Jeremy Affeldt | | 236 | 211 | 25 |
| 2006-05-18 | vs KCA | 41 | W 6-5 | 20-21 | 3 | 24,184 | Cliff Lee | Runelvys Hernandez | Cliff Lee | Runelvys Hernandez | Bob Wickman | 242 | 216 | 26 |
| 2006-05-19 | vs PIT | 42 | W 4-1 | 21-21 | 3 | 32,499 | CC Sabathia | Zach Duke | CC Sabathia | Zach Duke | | 246 | 217 | 29 |
| 2006-05-20 | vs PIT | 43 | L 6-9 | 21-22 | 3 | 30,799 | Jason Johnson | Ian Snell | Ian Snell | Jason Johnson | Mike Gonzalez | 252 | 226 | 26 |
| 2006-05-21 | vs PIT | 44 | W 3-2 | 22-22 | 3 | 31,589 | Paul Byrd | Paul Maholm | Bob Wickman | Mike Gonzalez | | 255 | 228 | 27 |
| 2006-05-23 | @ MIN | 45 | L 5-6 | 22-23 | 3 | 19,334 | Cliff Lee | Johan Santana | Joe Nathan | Guillermo Mota | | 260 | 234 | 26 |
| 2006-05-24 | @ MIN | 46 | W 11-0 | 23-23 | 3 | 22,789 | CC Sabathia | Brad Radke | CC Sabathia | Brad Radke | | 271 | 234 | 37 |
| 2006-05-26 | @ DET | 47 | L 3-8 | 23-24 | 3 | 31,241 | Jake Westbrook | Nate Robertson | Nate Robertson | Jake Westbrook | | 274 | 242 | 32 |
| 2006-05-27 | @ DET | 48 | L 1-3 | 23-25 | 3 | 37,102 | Paul Byrd | Justin Verlander | Justin Verlander | Paul Byrd | Todd Jones | 275 | 245 | 30 |
| 2006-05-28 | @ DET | 49 | W 9-0 | 24-25 | 3 | 37,908 | Jason Johnson | Kenny Rogers | Jason Johnson | Kenny Rogers | | 284 | 245 | 39 |
| 2006-05-29 | vs CHA | 50 | L 0-11 | 24-26 | 3 | 31,803 | Cliff Lee | Javier Vazquez | Javier Vazquez | Cliff Lee | | 284 | 256 | 28 |
| 2006-05-30 | vs CHA | 51 | W 4-3 | 25-26 | 3 | 20,944 | CC Sabathia | Mark Buehrle | CC Sabathia | Mark Buehrle | Bob Wickman | 288 | 259 | 29 |
| 2006-05-31 | vs CHA | 52 | W 5-0 | 26-26 | 3 | 21,671 | Jake Westbrook | Freddy Garcia | Jake Westbrook | Freddy Garcia | | 293 | 259 | 34 |
| 2006-06-01 | vs CHA | 53 | W 12-8 | 27-26 | 3 | 20,846 | Paul Byrd | Jose Contreras | Fernando Cabrera | Matt Thornton | | 305 | 267 | 38 |
| 2006-06-02 | vs ANA | 54 | L 3-10 | 27-27 | 3 | 22,957 | Jason Johnson | Jered Weaver | Jered Weaver | Jason Johnson | | 308 | 277 | 31 |
| 2006-06-03 | vs ANA | 55 | W 14-2 | 28-27 | 3 | 23,769 | Cliff Lee | Kelvim Escobar | Cliff Lee | Kelvim Escobar | | 322 | 279 | 43 |
| 2006-06-04 | vs ANA | 56 | L 2-14 | 28-28 | 3 | 19,148 | CC Sabathia | John Lackey | John Lackey | CC Sabathia | | 324 | 293 | 31 |
| 2006-06-06 | vs OAK | 57 | L 6-7 | 28-29 | 3 | 17,340 | Jake Westbrook | Barry Zito | Barry Zito | Rafael Betancourt | Huston Street | 330 | 300 | 30 |
| 2006-06-07 | vs OAK | 58 | W 11-2 | 29-29 | 3 | 20,311 | Paul Byrd | Joe Blanton | Paul Byrd | Joe Blanton | | 341 | 302 | 39 |
| 2006-06-08 | vs OAK | 59 | L 1-4 | 29-30 | 3 | 21,099 | Jason Johnson | Esteban Loaiza | Esteban Loaiza | Jason Johnson | Huston Street | 342 | 306 | 36 |
| 2006-06-09 | @ CHA | 60 | L 4-5 | 29-31 | 3 | 33,909 | Cliff Lee | Javier Vazquez | Matt Thornton | Rafael Betancourt | Bobby Jenks | 346 | 311 | 35 |
| 2006-06-10 | @ CHA | 61 | L 3-4 | 29-32 | 3 | 36,265 | CC Sabathia | Mark Buehrle | Agustin Montero | Bob Wickman | | 349 | 315 | 34 |
| 2006-06-11 | @ CHA | 62 | W 10-8 | 30-32 | 3 | 34,410 | Jake Westbrook | Freddy Garcia | Jake Westbrook | Freddy Garcia | Bob Wickman | 359 | 323 | 36 |
| 2006-06-13 | @ NYA | 63 | L 0-1 | 30-33 | 3 | 50,365 | Paul Byrd | Chien-Ming Wang | Chien-Ming Wang | Paul Byrd | Mariano Rivera | 359 | 324 | 35 |
| 2006-06-14 | @ NYA | 64 | L 1-6 | 30-34 | 3 | 53,448 | Jason Johnson | Randy Johnson | Randy Johnson | Jason Johnson | | 360 | 330 | 30 |
| 2006-06-15 | @ NYA | 65 | W 8-4 | 31-34 | 3 | 54,648 | Cliff Lee | Mike Mussina | Cliff Lee | Mike Mussina | | 368 | 334 | 34 |
| 2006-06-16 | @ MIL | 66 | L 4-6 | 31-35 | 4 | 33,178 | CC Sabathia | Chris Capuano | Chris Capuano | CC Sabathia | Derrick Turnbow | 372 | 340 | 32 |
| 2006-06-17 | @ MIL | 67 | L 2-3 | 31-36 | 4 | 42,069 | Jake Westbrook | David Bush | Jose Capellan | Bob Wickman | | 374 | 343 | 31 |
| 2006-06-18 | @ MIL | 68 | L 3-6 | 31-37 | 4 | 43,391 | Paul Byrd | Zach Jackson | Derrick Turnbow | Rafael Betancourt | | 377 | 349 | 28 |
| 2006-06-19 | vs CHN | 69 | L 8-12 | 31-38 | 4 | 26,769 | Jason Johnson | Sean Marshall | Sean Marshall | Jason Johnson | | 385 | 361 | 24 |
| 2006-06-20 | vs CHN | 70 | W 4-2 | 32-38 | 4 | 25,049 | Cliff Lee | Greg Maddux | Cliff Lee | Greg Maddux | Bob Wickman | 389 | 363 | 26 |
| 2006-06-21 | vs CHN | 71 | L 2-9 | 32-39 | 4 | 27,182 | CC Sabathia | Carlos Zambrano | Carlos Zambrano | CC Sabathia | | 391 | 372 | 19 |
| 2006-06-23 | vs CIN | 72 | L 0-3 | 32-40 | 4 | 32,927 | Jake Westbrook | Aaron Harang | Aaron Harang | Jake Westbrook | | 391 | 375 | 16 |
| 2006-06-24 | vs CIN | 73 | W 4-0 | 33-40 | 4 | 33,072 | Paul Byrd | Bronson Arroyo | Paul Byrd | Bronson Arroyo | | 395 | 375 | 20 |
| 2006-06-25 | vs CIN | 74 | L 2-4 | 33-41 | 4 | 33,139 | Jeremy Sowers | Elizardo Ramirez | Elizardo Ramirez | Jeremy Sowers | Todd Coffey | 397 | 379 | 18 |
| 2006-06-26 | @ SLN | 75 | W 10-3 | 34-41 | 4 | 44,659 | Cliff Lee | Jason Marquis | Cliff Lee | Jason Marquis | | 407 | 382 | 25 |
| 2006-06-27 | @ SLN | 76 | W 3-1 | 35-41 | 4 | 44,446 | CC Sabathia | Anthony Reyes | CC Sabathia | Anthony Reyes | Bob Wickman | 410 | 383 | 27 |
| 2006-06-28 | @ SLN | 77 | L 4-5 | 35-42 | 4 | 44,628 | Jake Westbrook | Chris Carpenter | Jason Isringhausen | Bob Wickman | | 414 | 388 | 26 |
| 2006-06-30 | @ CIN | 78 | L 8-9 | 35-43 | 4 | 34,930 | Paul Byrd | Elizardo Ramirez | Kent Mercker | Bob Wickman | | 422 | 397 | 25 |
| 2006-07-01 | @ CIN | 79 | W 12-7 | 36-43 | 4 | 40,692 | Cliff Lee | Joe Mays | Cliff Lee | Joe Mays | | 434 | 404 | 30 |
| 2006-07-02 | @ CIN | 80 | W 6-3 | 37-43 | 4 | 36,849 | CC Sabathia | Eric Milton | Guillermo Mota | David Weathers | Bob Wickman | 440 | 407 | 33 |
| 2006-07-03 | vs NYA | 81 | W 5-2 | 38-43 | 4 | 42,706 | Jeremy Sowers | Chien-Ming Wang | Jeremy Sowers | Chien-Ming Wang | Bob Wickman | 445 | 409 | 36 |
| 2006-07-04 | vs NYA | 82 | W 19-1 | 39-43 | 4 | 29,638 | Jake Westbrook | Shawn Chacon | Jake Westbrook | Shawn Chacon | | 464 | 410 | 54 |
| 2006-07-05 | vs NYA | 83 | L 3-11 | 39-44 | 4 | 31,265 | Paul Byrd | Mike Mussina | Mike Mussina | Paul Byrd | | 467 | 421 | 46 |
| 2006-07-06 | vs NYA | 84 | L 4-10 | 39-45 | 4 | 34,982 | Cliff Lee | Randy Johnson | Randy Johnson | Cliff Lee | | 471 | 431 | 40 |
| 2006-07-07 | vs BAL | 85 | W 9-0 | 40-45 | 4 | 27,110 | CC Sabathia | Kris Benson | CC Sabathia | Kris Benson | | 480 | 431 | 49 |
| 2006-07-08 | vs BAL | 86 | L 4-7 | 40-46 | 4 | 28,902 | Jeremy Sowers | Erik Bedard | Erik Bedard | Jeremy Sowers | Chris Ray | 484 | 438 | 46 |
| 2006-07-09 | vs BAL | 87 | L 4-5 | 40-47 | 4 | 26,452 | Jake Westbrook | Rodrigo Lopez | Kurt Birkins | Fausto Carmona | Chris Ray | 488 | 443 | 45 |
| 2006-07-13 | @ MIN | 88 | W 6-4 | 41-47 | 4 | 21,085 | Cliff Lee | Francisco Liriano | Cliff Lee | Francisco Liriano | Bob Wickman | 494 | 447 | 47 |
| 2006-07-14 | @ MIN | 89 | L 2-3 | 41-48 | 4 | 21,279 | Paul Byrd | Brad Radke | Joe Nathan | Edward Mujica | | 496 | 450 | 46 |
| 2006-07-15 | @ MIN | 90 | L 2-6 | 41-49 | 4 | 33,904 | CC Sabathia | Johan Santana | Johan Santana | CC Sabathia | | 498 | 456 | 42 |
| 2006-07-16 | @ MIN | 91 | L 2-5 | 41-50 | 4 | 31,838 | Jeremy Sowers | Carlos Silva | Carlos Silva | Jeremy Sowers | Joe Nathan | 500 | 461 | 39 |
| 2006-07-17 | @ ANA | 92 | L 5-10 | 41-51 | 4 | 43,921 | Jake Westbrook | Dustin Moseley | Dustin Moseley | Jake Westbrook | | 505 | 471 | 34 |
| 2006-07-18 | @ ANA | 93 | L 5-7 | 41-52 | 4 | 44,020 | Cliff Lee | Joe Saunders | Joe Saunders | Cliff Lee | Francisco Rodriguez | 510 | 478 | 32 |
| 2006-07-19 | @ ANA | 94 | W 6-4 | 42-52 | 4 | 43,744 | Paul Byrd | John Lackey | Paul Byrd | John Lackey | Bob Wickman | 516 | 482 | 34 |
| 2006-07-21 | vs MIN | 95 | L 6-14 | 42-53 | 4 | 29,695 | CC Sabathia | Carlos Silva | Dennys Reyes | CC Sabathia | | 522 | 496 | 26 |
| 2006-07-22 | vs MIN | 96 | W 11-0 | 43-53 | 4 | 26,895 | Jeremy Sowers | Scott Baker | Jeremy Sowers | Scott Baker | | 533 | 496 | 37 |
| 2006-07-23 | vs MIN | 97 | L 1-3 | 43-54 | 4 | 25,889 | Jake Westbrook | Francisco Liriano | Francisco Liriano | Jake Westbrook | Joe Nathan | 534 | 499 | 35 |
| 2006-07-24 | vs DET | 98 | L 7-9 | 43-55 | 4 | 19,045 | Cliff Lee | Jeremy Bonderman | Jeremy Bonderman | Cliff Lee | Todd Jones | 541 | 508 | 33 |
| 2006-07-25 | vs DET | 99 | W 12-7 | 44-55 | 4 | 28,085 | Paul Byrd | Kenny Rogers | Jason Davis | Kenny Rogers | | 553 | 515 | 38 |
| 2006-07-26 | vs DET | 100 | L 1-4 | 44-56 | 4 | 31,220 | CC Sabathia | Justin Verlander | Justin Verlander | CC Sabathia | Todd Jones | 554 | 519 | 35 |
| 2006-07-28 | vs SEA | 101 | W 1-0 | 45-56 | 4 | 25,045 | Jeremy Sowers | Felix Hernandez | Jeremy Sowers | Felix Hernandez | | 555 | 519 | 36 |
| 2006-07-29 | vs SEA | 102 | L 1-3 | 45-57 | 4 | 27,876 | Jake Westbrook | Jarrod Washburn | Jarrod Washburn | Jake Westbrook | J.J. Putz | 556 | 522 | 34 |
| 2006-07-30 | vs SEA | 103 | L 3-7 | 45-58 | 4 | 23,146 | Cliff Lee | Joel Pineiro | Jake Woods | Fausto Carmona | J.J. Putz | 559 | 529 | 30 |
| 2006-07-31 | @ BOS | 104 | L 8-9 | 45-59 | 4 | 36,387 | Paul Byrd | David Wells | Kyle Snyder | Fausto Carmona | | 567 | 538 | 29 |
| 2006-08-01 | @ BOS | 105 | W 6-3 | 46-59 | 4 | 36,328 | CC Sabathia | Jason Johnson | CC Sabathia | Jason Johnson | | 573 | 541 | 32 |
| 2006-08-02 | @ BOS | 106 | L 5-6 | 46-60 | 4 | 36,022 | Jeremy Sowers | Jon Lester | Jonathan Papelbon | Fausto Carmona | | 578 | 547 | 31 |
| 2006-08-03 | @ BOS | 107 | W 7-6 | 47-60 | 4 | 36,557 | Jake Westbrook | Josh Beckett | Jake Westbrook | Josh Beckett | Jason Davis | 585 | 553 | 32 |
| 2006-08-04 | @ DET | 108 | L 6-7 | 47-61 | 4 | 41,502 | Cliff Lee | Jeremy Bonderman | Roman Colon | Fernando Cabrera | Todd Jones | 591 | 560 | 31 |
| 2006-08-05 | @ DET | 109 | L 3-4 | 47-62 | 4 | 43,015 | Paul Byrd | Kenny Rogers | Joel Zumaya | Fausto Carmona | | 594 | 564 | 30 |
| 2006-08-06 | @ DET | 110 | L 0-1 | 47-63 | 4 | 39,178 | CC Sabathia | Wil Ledezma | Wil Ledezma | CC Sabathia | Todd Jones | 594 | 565 | 29 |
| 2006-08-08 | vs ANA | 111 | L 4-5 | 47-64 | 4 | 23,293 | Jeremy Sowers | Jered Weaver | Brendan Donnelly | Rafael Betancourt | Francisco Rodriguez | 598 | 570 | 28 |
| 2006-08-09 | vs ANA | 112 | W 4-0 | 48-64 | 4 | 18,804 | Jake Westbrook | John Lackey | Jake Westbrook | John Lackey | | 602 | 570 | 32 |
| 2006-08-10 | vs ANA | 113 | W 14-2 | 49-64 | 4 | 24,362 | Cliff Lee | Ervin Santana | Cliff Lee | Ervin Santana | | 616 | 572 | 44 |
| 2006-08-11 | vs KCA | 114 | W 4-3 | 50-64 | 4 | 30,929 | Paul Byrd | Adam Bernero | Fernando Cabrera | Ambiorix Burgos | | 620 | 575 | 45 |
| 2006-08-12 | vs KCA | 115 | W 5-4 | 52-64 | 4 | 17,079 | CC Sabathia | Odalis Perez | Rafael Betancourt | Joe Nelson | | 625 | 579 | 46 |
| 2006-08-12 | vs KCA | 116 | W 6-5 | 52-64 | 4 | 28,842 | Jeremy Guthrie | Jorge de la Rosa | Brian Sikorski | Jimmy Gobble | | 631 | 584 | 47 |
| 2006-08-13 | vs KCA | 117 | W 13-0 | 53-64 | 4 | 25,251 | Jeremy Sowers | Luke Hudson | Jeremy Sowers | Luke Hudson | | 644 | 584 | 60 |
| 2006-08-15 | @ MIN | 118 | L 1-4 | 53-65 | 4 | 34,854 | Jake Westbrook | Johan Santana | Johan Santana | Jake Westbrook | | 645 | 588 | 57 |
| 2006-08-16 | @ MIN | 119 | L 2-7 | 53-66 | 4 | 42,328 | Cliff Lee | Carlos Silva | Pat Neshek | Fausto Carmona | | 647 | 595 | 52 |
| 2006-08-17 | @ MIN | 120 | W 3-2 | 54-66 | 4 | 27,664 | Paul Byrd | Matt Garza | Paul Byrd | Matt Garza | | 650 | 597 | 53 |
| 2006-08-18 | @ TBA | 121 | L 5-6 | 54-67 | 4 | 15,405 | CC Sabathia | Casey Fossum | Seth McClung | Brian Sikorski | | 655 | 603 | 52 |
| 2006-08-19 | @ TBA | 122 | W 5-3 | 55-67 | 4 | 17,865 | Jeremy Sowers | Tim Corcoran | Jeremy Sowers | Tim Corcoran | Tom Mastny | 660 | 606 | 54 |
| 2006-08-20 | @ TBA | 123 | W 9-4 | 56-67 | 4 | 19,938 | Jake Westbrook | Jae Weong Seo | Jake Westbrook | Chad Orvella | | 669 | 610 | 59 |
| 2006-08-22 | @ KCA | 124 | L 2-5 | 56-68 | 4 | 13,270 | Cliff Lee | Odalis Perez | Odalis Perez | Cliff Lee | Joe Nelson | 671 | 615 | 56 |
| 2006-08-23 | @ KCA | 125 | W 15-13 | 57-68 | 4 | 12,671 | Paul Byrd | Jorge de la Rosa | Rafael Betancourt | Andy Sisco | Tom Mastny | 686 | 628 | 58 |
| 2006-08-24 | @ KCA | 126 | W 8-4 | 58-68 | 4 | 13,098 | CC Sabathia | Mark Redman | CC Sabathia | Jimmy Gobble | | 694 | 632 | 62 |
| 2006-08-25 | vs DET | 127 | W 4-2 | 59-68 | 4 | 33,416 | Jeremy Sowers | Jeremy Bonderman | Jeremy Sowers | Jeremy Bonderman | Rafael Betancourt | 698 | 634 | 64 |
| 2006-08-26 | vs DET | 128 | W 8-5 | 60-68 | 4 | 29,138 | Jake Westbrook | Justin Verlander | Jake Westbrook | Justin Verlander | Tom Mastny | 706 | 639 | 67 |
| 2006-08-27 | vs DET | 129 | L 1-7 | 60-69 | 4 | 28,342 | Cliff Lee | Kenny Rogers | Kenny Rogers | Cliff Lee | | 707 | 646 | 61 |
| 2006-08-28 | vs TOR | 130 | W 6-4 | 61-69 | 4 | 19,623 | Paul Byrd | A.J. Burnett | Paul Byrd | A.J. Burnett | Tom Mastny | 713 | 650 | 63 |
| 2006-08-29 | vs TOR | 131 | W 5-2 | 62-69 | 4 | 21,563 | CC Sabathia | Gustavo Chacin | CC Sabathia | Brandon League | | 718 | 652 | 66 |
| 2006-08-30 | vs TOR | 132 | W 3-2 | 63-69 | 4 | 22,065 | Jeremy Sowers | Shaun Marcum | Rafael Betancourt | B.J. Ryan | | 721 | 654 | 67 |
| 2006-09-01 | @ TEX | 133 | W 7-2 | 64-69 | 4 | 23,776 | Jake Westbrook | Vicente Padilla | Jake Westbrook | Vicente Padilla | | 728 | 656 | 72 |
| 2006-09-02 | @ TEX | 134 | W 6-5 | 65-69 | 4 | 40,222 | Cliff Lee | Edinson Volquez | Cliff Lee | Edinson Volquez | Tom Mastny | 734 | 661 | 73 |
| 2006-09-03 | @ TEX | 135 | L 2-5 | 65-70 | 4 | 19,667 | Paul Byrd | Kevin Millwood | Kevin Millwood | Paul Byrd | Akinori Otsuka | 736 | 666 | 70 |
| 2006-09-04 | @ TOR | 136 | L 3-4 | 65-71 | 4 | 27,864 | CC Sabathia | Shaun Marcum | Brandon League | CC Sabathia | B.J. Ryan | 739 | 670 | 69 |
| 2006-09-05 | @ TOR | 137 | W 7-2 | 66-71 | 4 | 18,517 | Jeremy Sowers | Roy Halladay | Jeremy Sowers | Jeremy Accardo | | 746 | 672 | 74 |
| 2006-09-06 | @ TOR | 138 | L 2-3 | 66-72 | 4 | 20,406 | Jake Westbrook | Ted Lilly | Ted Lilly | Jake Westbrook | B.J. Ryan | 748 | 675 | 73 |
| 2006-09-07 | @ CHA | 139 | W 9-1 | 67-72 | 4 | 34,671 | Cliff Lee | Mark Buehrle | Cliff Lee | Mark Buehrle | | 757 | 676 | 81 |
| 2006-09-08 | @ CHA | 140 | L 6-7 | 67-73 | 4 | 37,188 | Paul Byrd | Freddy Garcia | Matt Thornton | Tom Mastny | | 763 | 683 | 80 |
| 2006-09-09 | @ CHA | 141 | L 8-10 | 67-74 | 4 | 38,422 | Fausto Carmona | Jon Garland | Jon Garland | Fausto Carmona | Matt Thornton | 771 | 693 | 78 |
| 2006-09-10 | @ CHA | 142 | W 5-2 | 68-74 | 4 | 37,723 | CC Sabathia | Javier Vazquez | CC Sabathia | Brandon McCarthy | | 776 | 695 | 81 |
| 2006-09-12 | vs KCA | 143 | L 3-5 | 68-75 | 4 | 18,883 | Jeremy Sowers | Runelvys Hernandez | Runelvys Hernandez | Jeremy Sowers | Joe Nelson | 779 | 700 | 79 |
| 2006-09-13 | vs KCA | 144 | L 2-6 | 68-76 | 4 | 20,089 | Jake Westbrook | Jorge de la Rosa | Jorge de la Rosa | Jake Westbrook | | 781 | 706 | 75 |
| 2006-09-14 | vs MIN | 145 | L 4-9 | 68-77 | 4 | 21,424 | Cliff Lee | Boof Bonser | Jesse Crain | Jason Davis | | 785 | 715 | 70 |
| 2006-09-15 | vs MIN | 146 | W 5-4 | 69-77 | 4 | 32,473 | Fausto Carmona | Johan Santana | Fernando Cabrera | Pat Neshek | | 790 | 719 | 71 |
| 2006-09-16 | vs MIN | 147 | L 1-4 | 69-78 | 4 | 26,757 | CC Sabathia | Carlos Silva | Carlos Silva | CC Sabathia | Joe Nathan | 791 | 723 | 68 |
| 2006-09-17 | vs MIN | 148 | L 1-6 | 69-79 | 4 | 20,324 | Paul Byrd | Scott Baker | Scott Baker | Paul Byrd | Matt Guerrier | 792 | 729 | 63 |
| 2006-09-18 | @ OAK | 149 | W 7-2 | 70-79 | 4 | 17,352 | Jake Westbrook | Dan Haren | Jake Westbrook | Dan Haren | | 799 | 731 | 68 |
| 2006-09-19 | @ OAK | 150 | L 3-7 | 70-80 | 4 | 15,866 | Cliff Lee | Kirk Saarloos | Chad Gaudin | Cliff Lee | | 802 | 738 | 64 |
| 2006-09-20 | @ OAK | 151 | L 3-4 | 70-81 | 4 | 25,131 | Fausto Carmona | Esteban Loaiza | Esteban Loaiza | Fernando Cabrera | Huston Street | 805 | 742 | 63 |
| 2006-09-21 | @ OAK | 152 | L 4-7 | 70-82 | 4 | 20,452 | CC Sabathia | Rich Harden | Chad Gaudin | CC Sabathia | Huston Street | 809 | 749 | 60 |
| 2006-09-22 | @ TEX | 153 | L 4-12 | 70-83 | 4 | 26,284 | Paul Byrd | Adam Eaton | Adam Eaton | Paul Byrd | | 813 | 761 | 52 |
| 2006-09-23 | @ TEX | 154 | W 6-3 | 71-83 | 4 | 38,351 | Brian Slocum | Vicente Padilla | Matt Miller | Vicente Padilla | Rafael Betancourt | 819 | 764 | 55 |
| 2006-09-24 | @ TEX | 155 | W 11-6 | 72-83 | 4 | 36,617 | Jake Westbrook | Kevin Millwood | Jake Westbrook | Kevin Millwood | | 830 | 770 | 60 |
| 2006-09-25 | vs CHA | 156 | W 14-1 | 73-83 | 4 | 15,913 | Cliff Lee | Jon Garland | Cliff Lee | Jon Garland | | 844 | 771 | 73 |
| 2006-09-26 | vs CHA | 157 | W 6-0 | 74-83 | 4 | 16,080 | CC Sabathia | Javier Vazquez | CC Sabathia | Javier Vazquez | | 850 | 771 | 79 |
| 2006-09-27 | vs CHA | 158 | L 1-2 | 74-84 | 4 | 16,404 | Fausto Carmona | Brandon McCarthy | Brandon McCarthy | Fausto Carmona | Charlie Haeger | 851 | 773 | 78 |
| 2006-09-28 | vs TBA | 159 | W 5-4 | 75-84 | 4 | 14,503 | Paul Byrd | J.P. Howell | Paul Byrd | Ruddy Lugo | Rafael Betancourt | 856 | 777 | 79 |
| 2006-09-29 | vs TBA | 160 | W 2-1 | 76-84 | 4 | 19,983 | Brian Slocum | Brian Stokes | Brian Sikorski | Dan Miceli | | 858 | 778 | 80 |
| 2006-09-30 | vs TBA | 161 | W 6-1 | 77-84 | 4 | 17,562 | Jake Westbrook | Jae Weong Seo | Jake Westbrook | Jae Weong Seo | | 864 | 779 | 85 |
| 2006-10-01 | vs TBA | 162 | W 6-3 | 78-84 | 4 | 22,079 | Cliff Lee | Jason Hammel | Cliff Lee | Jason Hammel | | 870 | 782 | 88 |