| 2006-04-02 | vs CLE | 1 | W 10-4 | 1-0 | 1 | 38,802 | Mark Buehrle | CC Sabathia | Brandon McCarthy | Fernando Cabrera | | 10 | 4 | 6 |
| 2006-04-04 | vs CLE | 2 | L 2-8 | 1-1 | 2 | 37,591 | Freddy Garcia | Jake Westbrook | Jake Westbrook | Freddy Garcia | | 12 | 12 | 0 |
| 2006-04-05 | vs CLE | 3 | L 3-4 | 1-2 | 4 | 33,586 | Jose Contreras | Cliff Lee | Danny Graves | Neal Cotts | Bob Wickman | 15 | 16 | -1 |
| 2006-04-07 | @ KCA | 4 | L 7-11 | 1-3 | 4 | 23,204 | Jon Garland | Jeremy Affeldt | Mike Wood | Jon Garland | | 22 | 27 | -5 |
| 2006-04-08 | @ KCA | 5 | L 3-4 | 1-4 | 4 | 18,031 | Javier Vazquez | Denny Bautista | Elmer Dessens | Cliff Politte | Ambiorix Burgos | 25 | 31 | -6 |
| 2006-04-09 | @ KCA | 6 | W 3-1 | 2-4 | 4 | 15,094 | Mark Buehrle | Scott Elarton | Mark Buehrle | Scott Elarton | Bobby Jenks | 28 | 32 | -4 |
| 2006-04-10 | @ DET | 7 | W 5-3 | 3-4 | 3 | 44,179 | Freddy Garcia | Jeremy Bonderman | Freddy Garcia | Jeremy Bonderman | Bobby Jenks | 33 | 35 | -2 |
| 2006-04-12 | @ DET | 8 | W 4-3 | 4-4 | 3 | 12,601 | Jose Contreras | Nate Robertson | Jose Contreras | Nate Robertson | Bobby Jenks | 37 | 38 | -1 |
| 2006-04-13 | @ DET | 9 | W 13-9 | 5-4 | 2 | 14,027 | Jon Garland | Justin Verlander | Jon Garland | Justin Verlander | | 50 | 47 | 3 |
| 2006-04-14 | vs TOR | 10 | L 7-13 | 5-5 | 3 | 31,418 | Javier Vazquez | Scott Downs | Pete Walker | Javier Vazquez | | 57 | 60 | -3 |
| 2006-04-15 | vs TOR | 11 | W 4-2 | 6-5 | 2 | 33,247 | Mark Buehrle | A.J. Burnett | Mark Buehrle | A.J. Burnett | Bobby Jenks | 61 | 62 | -1 |
| 2006-04-16 | vs TOR | 12 | W 6-4 | 7-5 | 1 | 27,137 | Freddy Garcia | Josh Towers | Freddy Garcia | Josh Towers | | 67 | 66 | 1 |
| 2006-04-17 | vs KCA | 13 | W 9-0 | 8-5 | 1 | 27,889 | Jose Contreras | Joe Mays | Jose Contreras | Joe Mays | | 76 | 66 | 10 |
| 2006-04-18 | vs KCA | 14 | W 4-1 | 9-5 | 1 | 21,901 | Jon Garland | Jeremy Affeldt | Jon Garland | Jeremy Affeldt | Bobby Jenks | 80 | 67 | 13 |
| 2006-04-19 | vs KCA | 15 | W 4-0 | 10-5 | 1 | 26,327 | Javier Vazquez | Scott Elarton | Javier Vazquez | Scott Elarton | Bobby Jenks | 84 | 67 | 17 |
| 2006-04-21 | vs MIN | 16 | W 7-1 | 11-5 | 1 | 31,287 | Mark Buehrle | Johan Santana | Mark Buehrle | Johan Santana | | 91 | 68 | 23 |
| 2006-04-22 | vs MIN | 17 | W 9-2 | 12-5 | 1 | 38,955 | Freddy Garcia | Brad Radke | Freddy Garcia | Brad Radke | | 100 | 70 | 30 |
| 2006-04-23 | vs MIN | 18 | W 7-3 | 13-5 | 1 | 38,102 | Jose Contreras | Carlos Silva | Jose Contreras | Carlos Silva | | 107 | 73 | 34 |
| 2006-04-24 | @ SEA | 19 | L 3-4 | 13-6 | 1 | 20,390 | Jon Garland | Jamie Moyer | Julio Mateo | Brandon McCarthy | | 110 | 77 | 33 |
| 2006-04-25 | @ SEA | 20 | W 13-3 | 14-6 | 1 | 20,451 | Javier Vazquez | Joel Pineiro | Javier Vazquez | Joel Pineiro | Boone Logan | 123 | 80 | 43 |
| 2006-04-26 | @ SEA | 21 | L 1-5 | 14-7 | 1 | 23,848 | Mark Buehrle | Jarrod Washburn | Jarrod Washburn | Mark Buehrle | | 124 | 85 | 39 |
| 2006-04-28 | @ ANA | 22 | W 8-5 | 15-7 | 1 | 43,940 | Freddy Garcia | Jeff Weaver | Freddy Garcia | Jeff Weaver | | 132 | 90 | 42 |
| 2006-04-29 | @ ANA | 23 | W 2-1 | 16-7 | 1 | 44,065 | Jose Contreras | Kelvim Escobar | Jose Contreras | Kelvim Escobar | Bobby Jenks | 134 | 91 | 43 |
| 2006-04-30 | @ ANA | 24 | W 6-5 | 17-7 | 1 | 44,135 | Jon Garland | Ervin Santana | Cliff Politte | Scot Shields | Neal Cotts | 140 | 96 | 44 |
| 2006-05-01 | @ CLE | 25 | W 8-6 | 18-7 | 1 | 17,845 | Javier Vazquez | Cliff Lee | Javier Vazquez | Cliff Lee | Bobby Jenks | 148 | 102 | 46 |
| 2006-05-02 | @ CLE | 26 | L 1-7 | 18-8 | 1 | 22,630 | Mark Buehrle | CC Sabathia | CC Sabathia | Mark Buehrle | | 149 | 109 | 40 |
| 2006-05-03 | vs SEA | 27 | W 6-5 | 19-8 | 1 | 27,569 | Freddy Garcia | Gil Meche | Bobby Jenks | Jake Woods | | 155 | 114 | 41 |
| 2006-05-04 | vs SEA | 28 | W 4-1 | 20-8 | 1 | 26,313 | Jose Contreras | Felix Hernandez | Jose Contreras | Felix Hernandez | Bobby Jenks | 159 | 115 | 44 |
| 2006-05-05 | vs KCA | 29 | L 4-5 | 21-8 | 1 | 33,628 | Jon Garland | Scott Elarton | Elmer Dessens | Bobby Jenks | Ambiorix Burgos | 163 | 120 | 43 |
| 2006-05-06 | vs KCA | 30 | W 9-2 | 22-8 | 1 | 38,593 | Javier Vazquez | Runelvys Hernandez | Javier Vazquez | Runelvys Hernandez | | 172 | 122 | 50 |
| 2006-05-07 | vs KCA | 31 | W 3-2 | 23-8 | 1 | 38,870 | Mark Buehrle | Mark Redman | Brandon McCarthy | Elmer Dessens | Bobby Jenks | 175 | 124 | 51 |
| 2006-05-09 | vs ANA | 32 | W 9-1 | 24-8 | 1 | 36,539 | Freddy Garcia | Kevin Gregg | Freddy Garcia | Kevin Gregg | | 184 | 125 | 59 |
| 2006-05-10 | vs ANA | 33 | L 5-12 | 24-9 | 1 | 31,034 | Charlie Haeger | Ervin Santana | Ervin Santana | Charlie Haeger | Francisco Rodriguez | 189 | 137 | 52 |
| 2006-05-12 | @ MIN | 34 | L 1-10 | 24-10 | 1 | 30,473 | Jon Garland | Johan Santana | Johan Santana | Jon Garland | | 190 | 147 | 43 |
| 2006-05-13 | @ MIN | 35 | L 4-8 | 24-11 | 1 | 33,021 | Javier Vazquez | Brad Radke | Brad Radke | Javier Vazquez | | 194 | 155 | 39 |
| 2006-05-14 | @ MIN | 36 | W 9-7 | 25-11 | 1 | 21,796 | Mark Buehrle | Carlos Silva | Mark Buehrle | Carlos Silva | Bobby Jenks | 203 | 162 | 41 |
| 2006-05-15 | @ MIN | 37 | W 7-3 | 26-11 | 1 | 19,413 | Freddy Garcia | Scott Baker | Freddy Garcia | Scott Baker | | 210 | 165 | 45 |
| 2006-05-16 | @ TBA | 38 | L 7-10 | 26-12 | 1 | 11,566 | Brandon McCarthy | Scott Kazmir | Scott Kazmir | Brandon McCarthy | Tyler Walker | 217 | 175 | 42 |
| 2006-05-17 | @ TBA | 39 | W 5-2 | 27-12 | 1 | 11,607 | Jon Garland | Seth McClung | Jon Garland | Ruddy Lugo | Bobby Jenks | 222 | 177 | 45 |
| 2006-05-18 | @ TBA | 40 | L 4-5 | 27-13 | 1 | 22,665 | Javier Vazquez | Mark Hendrickson | Mark Hendrickson | Javier Vazquez | Tyler Walker | 226 | 182 | 44 |
| 2006-05-19 | vs CHN | 41 | W 6-1 | 28-13 | 1 | 39,301 | Mark Buehrle | Greg Maddux | Mark Buehrle | Greg Maddux | | 232 | 183 | 49 |
| 2006-05-20 | vs CHN | 42 | W 7-0 | 29-13 | 1 | 39,387 | Freddy Garcia | Rich Hill | Freddy Garcia | Rich Hill | | 239 | 183 | 56 |
| 2006-05-21 | vs CHN | 43 | L 4-7 | 29-14 | 1 | 38,645 | Jose Contreras | Carlos Zambrano | Carlos Zambrano | Neal Cotts | Ryan Dempster | 243 | 190 | 53 |
| 2006-05-22 | vs OAK | 44 | W 5-4 | 30-14 | 1 | 39,354 | Jon Garland | Barry Zito | Bobby Jenks | Ron Flores | | 248 | 194 | 54 |
| 2006-05-23 | vs OAK | 45 | W 9-3 | 31-14 | 1 | 38,860 | Javier Vazquez | Kirk Saarloos | Javier Vazquez | Kirk Saarloos | | 257 | 197 | 60 |
| 2006-05-24 | vs OAK | 46 | W 3-2 | 32-14 | 1 | 38,434 | Mark Buehrle | Dan Haren | Mark Buehrle | Dan Haren | Bobby Jenks | 260 | 199 | 61 |
| 2006-05-26 | @ TOR | 47 | L 2-8 | 32-15 | 2 | 22,729 | Freddy Garcia | Ted Lilly | Ted Lilly | Freddy Garcia | | 262 | 207 | 55 |
| 2006-05-27 | @ TOR | 48 | L 2-3 | 32-16 | 2 | 30,063 | Jose Contreras | Casey Janssen | Scott Schoeneweis | Jeff Nelson | | 264 | 210 | 54 |
| 2006-05-28 | @ TOR | 49 | W 7-5 | 33-16 | 2 | 35,277 | Jon Garland | Ty Taubenheim | Jon Garland | Ty Taubenheim | Bobby Jenks | 271 | 215 | 56 |
| 2006-05-29 | @ CLE | 50 | W 11-0 | 34-16 | 2 | 31,803 | Javier Vazquez | Cliff Lee | Javier Vazquez | Cliff Lee | | 282 | 215 | 67 |
| 2006-05-30 | @ CLE | 51 | L 3-4 | 34-17 | 2 | 20,944 | Mark Buehrle | CC Sabathia | CC Sabathia | Mark Buehrle | Bob Wickman | 285 | 219 | 66 |
| 2006-05-31 | @ CLE | 52 | L 0-5 | 34-18 | 2 | 21,671 | Freddy Garcia | Jake Westbrook | Jake Westbrook | Freddy Garcia | | 285 | 224 | 61 |
| 2006-06-01 | @ CLE | 53 | L 8-12 | 34-19 | 2 | 20,846 | Jose Contreras | Paul Byrd | Fernando Cabrera | Matt Thornton | | 293 | 236 | 57 |
| 2006-06-02 | vs TEX | 54 | L 3-4 | 34-20 | 2 | 32,802 | Jon Garland | Kameron Loe | Francisco Cordero | Brandon McCarthy | Akinori Otsuka | 296 | 240 | 56 |
| 2006-06-03 | vs TEX | 55 | W 8-6 | 35-20 | 2 | 38,697 | Javier Vazquez | Vicente Padilla | Javier Vazquez | Vicente Padilla | Bobby Jenks | 304 | 246 | 58 |
| 2006-06-04 | vs TEX | 56 | L 2-10 | 35-21 | 2 | 35,915 | Mark Buehrle | John Rheinecker | John Rheinecker | Mark Buehrle | | 306 | 256 | 50 |
| 2006-06-06 | vs DET | 57 | W 4-3 | 36-21 | 2 | 37,192 | Freddy Garcia | Nate Robertson | Brandon McCarthy | Fernando Rodney | Bobby Jenks | 310 | 259 | 51 |
| 2006-06-07 | vs DET | 58 | W 4-3 | 37-21 | 1 | 37,612 | Jose Contreras | Justin Verlander | Jose Contreras | Justin Verlander | Bobby Jenks | 314 | 262 | 52 |
| 2006-06-08 | vs DET | 59 | L 2-6 | 37-22 | 2 | 37,354 | Jon Garland | Kenny Rogers | Kenny Rogers | Jon Garland | | 316 | 268 | 48 |
| 2006-06-09 | vs CLE | 60 | W 5-4 | 38-22 | 1 | 33,909 | Javier Vazquez | Cliff Lee | Matt Thornton | Rafael Betancourt | Bobby Jenks | 321 | 272 | 49 |
| 2006-06-10 | vs CLE | 61 | W 4-3 | 39-22 | 1 | 36,265 | Mark Buehrle | CC Sabathia | Agustin Montero | Bob Wickman | | 325 | 275 | 50 |
| 2006-06-11 | vs CLE | 62 | L 8-10 | 39-23 | 2 | 34,410 | Freddy Garcia | Jake Westbrook | Jake Westbrook | Freddy Garcia | Bob Wickman | 333 | 285 | 48 |
| 2006-06-12 | @ TEX | 63 | W 8-3 | 40-23 | 2 | 29,182 | Jose Contreras | John Koronka | Jose Contreras | John Koronka | | 341 | 288 | 53 |
| 2006-06-13 | @ TEX | 64 | W 5-2 | 41-23 | 2 | 18,354 | Jon Garland | Kameron Loe | Jon Garland | Kameron Loe | Bobby Jenks | 346 | 290 | 56 |
| 2006-06-14 | @ TEX | 65 | L 0-8 | 41-24 | 2 | 28,776 | Javier Vazquez | Vicente Padilla | Vicente Padilla | Javier Vazquez | | 346 | 298 | 48 |
| 2006-06-15 | @ TEX | 66 | W 8-2 | 42-24 | 2 | 19,424 | Mark Buehrle | John Rheinecker | Mark Buehrle | John Rheinecker | | 354 | 300 | 54 |
| 2006-06-16 | @ CIN | 67 | W 12-4 | 43-24 | 2 | 32,673 | Freddy Garcia | Brandon Claussen | Freddy Garcia | Brandon Claussen | | 366 | 304 | 62 |
| 2006-06-17 | @ CIN | 68 | W 8-6 | 44-24 | 2 | 39,451 | Jose Contreras | Eric Milton | Matt Thornton | Todd Coffey | Bobby Jenks | 374 | 310 | 64 |
| 2006-06-18 | @ CIN | 69 | W 8-1 | 45-24 | 2 | 31,569 | Jon Garland | Aaron Harang | Jon Garland | Aaron Harang | | 382 | 311 | 71 |
| 2006-06-20 | vs SLN | 70 | W 20-6 | 46-24 | 2 | 39,463 | Javier Vazquez | Mark Mulder | Javier Vazquez | Mark Mulder | | 402 | 317 | 85 |
| 2006-06-21 | vs SLN | 71 | W 13-5 | 47-24 | 1 | 37,897 | Mark Buehrle | Jason Marquis | Mark Buehrle | Jason Marquis | | 415 | 322 | 93 |
| 2006-06-22 | vs SLN | 72 | W 1-0 | 48-24 | 1 | 39,509 | Freddy Garcia | Anthony Reyes | Freddy Garcia | Anthony Reyes | Bobby Jenks | 416 | 322 | 94 |
| 2006-06-23 | vs HOU | 73 | W 7-4 | 49-24 | 1 | 37,700 | Jose Contreras | Andy Pettitte | Jose Contreras | Andy Pettitte | Bobby Jenks | 423 | 326 | 97 |
| 2006-06-24 | vs HOU | 74 | W 6-5 | 50-24 | 1 | 38,377 | Jon Garland | Taylor Buchholz | Matt Thornton | Dan Wheeler | | 429 | 331 | 98 |
| 2006-06-25 | vs HOU | 75 | L 9-10 | 50-25 | 2 | 38,516 | Javier Vazquez | Roy Oswalt | Fernando Nieve | Brandon McCarthy | | 438 | 341 | 97 |
| 2006-06-27 | @ PIT | 76 | W 4-2 | 51-25 | 2 | 24,976 | Mark Buehrle | Ian Snell | Mark Buehrle | Ian Snell | Bobby Jenks | 442 | 343 | 99 |
| 2006-06-28 | @ PIT | 77 | W 4-3 | 52-25 | 2 | 23,118 | Freddy Garcia | Paul Maholm | Freddy Garcia | Paul Maholm | Bobby Jenks | 446 | 346 | 100 |
| 2006-06-29 | @ PIT | 78 | L 6-7 | 52-26 | 2 | 21,380 | Jose Contreras | Zach Duke | Mike Gonzalez | Cliff Politte | | 452 | 353 | 99 |
| 2006-06-30 | @ CHN | 79 | W 6-2 | 53-26 | 2 | 40,720 | Jon Garland | Sean Marshall | Jon Garland | Sean Marshall | | 458 | 355 | 103 |
| 2006-07-01 | @ CHN | 80 | W 8-6 | 54-26 | 2 | 41,027 | Javier Vazquez | Greg Maddux | Neal Cotts | Ryan Dempster | Bobby Jenks | 466 | 361 | 105 |
| 2006-07-02 | @ CHN | 81 | L 11-15 | 54-27 | 2 | 40,919 | Mark Buehrle | Carlos Zambrano | Carlos Zambrano | Mark Buehrle | Bob Howry | 477 | 376 | 101 |
| 2006-07-03 | vs BAL | 82 | L 1-8 | 54-28 | 2 | 38,829 | Freddy Garcia | Erik Bedard | Erik Bedard | Freddy Garcia | | 478 | 384 | 94 |
| 2006-07-04 | vs BAL | 83 | W 13-0 | 55-28 | 2 | 37,300 | Jose Contreras | Rodrigo Lopez | Jose Contreras | Rodrigo Lopez | | 491 | 384 | 107 |
| 2006-07-05 | vs BAL | 84 | W 4-2 | 56-28 | 2 | 38,872 | Jon Garland | Daniel Cabrera | Jon Garland | Daniel Cabrera | Bobby Jenks | 495 | 386 | 109 |
| 2006-07-06 | vs BAL | 85 | W 11-8 | 57-28 | 1 | 35,266 | Javier Vazquez | Russ Ortiz | Javier Vazquez | Russ Ortiz | Matt Thornton | 506 | 394 | 112 |
| 2006-07-07 | vs BOS | 86 | L 2-7 | 57-29 | 2 | 39,355 | Mark Buehrle | Jon Lester | Jon Lester | Mark Buehrle | | 508 | 401 | 107 |
| 2006-07-08 | vs BOS | 87 | L 6-9 | 57-30 | 2 | 39,497 | Freddy Garcia | Josh Beckett | Josh Beckett | David Riske | Jonathan Papelbon | 514 | 410 | 104 |
| 2006-07-09 | vs BOS | 88 | W 6-5 | 58-30 | 2 | 39,335 | Jose Contreras | Curt Schilling | Cliff Politte | Rudy Seanez | | 520 | 415 | 105 |
| 2006-07-14 | @ NYA | 89 | L 5-6 | 58-31 | 2 | 55,069 | Jose Contreras | Randy Johnson | Kyle Farnsworth | Jose Contreras | Mariano Rivera | 525 | 421 | 104 |
| 2006-07-15 | @ NYA | 90 | L 3-14 | 58-32 | 2 | 55,019 | Mark Buehrle | Mike Mussina | Mike Mussina | Mark Buehrle | | 528 | 435 | 93 |
| 2006-07-16 | @ NYA | 91 | L 4-6 | 58-33 | 2 | 54,781 | Freddy Garcia | Jaret Wright | Jaret Wright | Freddy Garcia | Mariano Rivera | 532 | 441 | 91 |
| 2006-07-18 | @ DET | 92 | W 7-1 | 59-33 | 2 | 39,153 | Jon Garland | Nate Robertson | Jon Garland | Nate Robertson | | 539 | 442 | 97 |
| 2006-07-19 | @ DET | 93 | L 2-5 | 59-34 | 2 | 39,593 | Javier Vazquez | Jeremy Bonderman | Jeremy Bonderman | Javier Vazquez | | 541 | 447 | 94 |
| 2006-07-20 | @ DET | 94 | L 1-2 | 59-35 | 2 | 41,075 | Jose Contreras | Kenny Rogers | Joel Zumaya | Jose Contreras | Todd Jones | 542 | 449 | 93 |
| 2006-07-21 | vs TEX | 95 | L 3-10 | 59-36 | 2 | 38,246 | Mark Buehrle | John Wasdin | Ron Mahay | Mark Buehrle | Rick Bauer | 545 | 459 | 86 |
| 2006-07-22 | vs TEX | 96 | L 1-3 | 59-37 | 2 | 39,250 | Freddy Garcia | John Koronka | Francisco Cordero | Bobby Jenks | Akinori Otsuka | 546 | 462 | 84 |
| 2006-07-23 | vs TEX | 97 | W 5-0 | 60-37 | 2 | 38,312 | Jon Garland | Vicente Padilla | Jon Garland | Vicente Padilla | | 551 | 462 | 89 |
| 2006-07-24 | vs MIN | 98 | L 4-7 | 60-38 | 2 | 39,750 | Javier Vazquez | Brad Radke | Brad Radke | Javier Vazquez | | 555 | 469 | 86 |
| 2006-07-25 | vs MIN | 99 | L 3-4 | 60-39 | 2 | 36,984 | Jose Contreras | Johan Santana | Johan Santana | Jose Contreras | Joe Nathan | 558 | 473 | 85 |
| 2006-07-26 | vs MIN | 100 | L 4-7 | 60-40 | 2 | 39,387 | Mark Buehrle | Carlos Silva | Carlos Silva | Mark Buehrle | Joe Nathan | 562 | 480 | 82 |
| 2006-07-28 | @ BAL | 101 | W 6-4 | 61-40 | 2 | 35,382 | Freddy Garcia | Erik Bedard | Matt Thornton | Chris Ray | Bobby Jenks | 568 | 484 | 84 |
| 2006-07-29 | @ BAL | 102 | W 13-11 | 62-40 | 2 | 34,598 | Jon Garland | Jim Johnson | Jon Garland | Jim Johnson | Bobby Jenks | 581 | 495 | 86 |
| 2006-07-30 | @ BAL | 103 | L 7-8 | 62-41 | 2 | 28,725 | Javier Vazquez | Bruce Chen | Eddy Rodriguez | Bobby Jenks | | 588 | 503 | 85 |
| 2006-07-31 | @ KCA | 104 | W 8-4 | 63-41 | 2 | 12,903 | Jose Contreras | Runelvys Hernandez | Jose Contreras | Runelvys Hernandez | | 596 | 507 | 89 |
| 2006-08-01 | @ KCA | 105 | W 7-5 | 64-41 | 2 | 11,609 | Mark Buehrle | Odalis Perez | David Riske | Ambiorix Burgos | Bobby Jenks | 603 | 512 | 91 |
| 2006-08-02 | @ KCA | 106 | L 3-7 | 64-42 | 2 | 10,901 | Freddy Garcia | Luke Hudson | Luke Hudson | Freddy Garcia | | 606 | 519 | 87 |
| 2006-08-04 | @ TOR | 107 | W 6-4 | 65-42 | 2 | 30,060 | Jon Garland | Roy Halladay | Jon Garland | Roy Halladay | Bobby Jenks | 612 | 523 | 89 |
| 2006-08-05 | @ TOR | 108 | W 7-1 | 66-42 | 2 | 35,117 | Javier Vazquez | Francisco Rosario | Javier Vazquez | Francisco Rosario | | 619 | 524 | 95 |
| 2006-08-06 | @ TOR | 109 | L 3-7 | 66-43 | 2 | 36,453 | Jose Contreras | A.J. Burnett | A.J. Burnett | Jose Contreras | | 622 | 531 | 91 |
| 2006-08-07 | vs ANA | 110 | L 3-6 | 66-44 | 2 | 37,477 | Mark Buehrle | Kelvim Escobar | Kelvim Escobar | Mark Buehrle | Francisco Rodriguez | 625 | 537 | 88 |
| 2006-08-08 | vs NYA | 111 | W 6-5 | 67-44 | 2 | 39,872 | Freddy Garcia | Chien-Ming Wang | Bobby Jenks | Scott Proctor | | 631 | 542 | 89 |
| 2006-08-09 | vs NYA | 112 | L 6-7 | 67-45 | 2 | 39,406 | Jon Garland | Randy Johnson | Randy Johnson | Jon Garland | Mariano Rivera | 637 | 549 | 88 |
| 2006-08-10 | vs NYA | 113 | W 5-4 | 68-45 | 2 | 39,289 | Javier Vazquez | Mike Mussina | Javier Vazquez | Mike Mussina | Bobby Jenks | 642 | 553 | 89 |
| 2006-08-11 | vs DET | 114 | W 5-0 | 69-45 | 2 | 39,378 | Jose Contreras | Justin Verlander | Jose Contreras | Justin Verlander | | 647 | 553 | 94 |
| 2006-08-12 | vs DET | 115 | W 4-3 | 70-45 | 2 | 38,873 | Mark Buehrle | Kenny Rogers | Mike MacDougal | Kenny Rogers | Bobby Jenks | 651 | 556 | 95 |
| 2006-08-13 | vs DET | 116 | W 7-3 | 71-45 | 2 | 38,931 | Freddy Garcia | Zach Miner | Freddy Garcia | Zach Miner | Bobby Jenks | 658 | 559 | 99 |
| 2006-08-14 | vs KCA | 117 | W 12-2 | 72-45 | 2 | 39,398 | Jon Garland | Mark Redman | Jon Garland | Mark Redman | | 670 | 561 | 109 |
| 2006-08-15 | vs KCA | 118 | L 2-4 | 72-46 | 2 | 35,690 | Javier Vazquez | Runelvys Hernandez | Runelvys Hernandez | Javier Vazquez | Joe Nelson | 672 | 565 | 107 |
| 2006-08-16 | vs KCA | 119 | L 4-10 | 72-47 | 2 | 36,998 | Jose Contreras | Adam Bernero | Adam Bernero | Jose Contreras | | 676 | 575 | 101 |
| 2006-08-17 | vs KCA | 120 | W 5-4 | 73-47 | 2 | 37,839 | Mark Buehrle | Odalis Perez | Mark Buehrle | Odalis Perez | Bobby Jenks | 681 | 579 | 102 |
| 2006-08-18 | @ MIN | 121 | L 3-7 | 73-48 | 2 | 43,204 | Freddy Garcia | Boof Bonser | Pat Neshek | Freddy Garcia | | 684 | 586 | 98 |
| 2006-08-19 | @ MIN | 122 | W 4-1 | 74-48 | 2 | 46,215 | Jon Garland | Brad Radke | Jon Garland | Brad Radke | Bobby Jenks | 688 | 587 | 101 |
| 2006-08-20 | @ MIN | 123 | L 3-7 | 74-49 | 2 | 42,537 | Javier Vazquez | Johan Santana | Johan Santana | Javier Vazquez | | 691 | 594 | 97 |
| 2006-08-21 | @ DET | 124 | L 1-7 | 74-50 | 2 | 39,278 | Jose Contreras | Justin Verlander | Justin Verlander | Jose Contreras | | 692 | 601 | 91 |
| 2006-08-22 | @ DET | 125 | L 0-4 | 74-51 | 2 | 39,361 | Mark Buehrle | Kenny Rogers | Kenny Rogers | Mark Buehrle | | 692 | 605 | 87 |
| 2006-08-23 | @ DET | 126 | W 7-5 | 75-51 | 2 | 40,187 | Freddy Garcia | Zach Miner | Freddy Garcia | Zach Miner | Bobby Jenks | 699 | 610 | 89 |
| 2006-08-24 | @ DET | 127 | W 10-0 | 76-51 | 2 | 41,565 | Jon Garland | Nate Robertson | Jon Garland | Nate Robertson | | 709 | 610 | 99 |
| 2006-08-25 | vs MIN | 128 | L 4-5 | 76-52 | 2 | 35,931 | Javier Vazquez | Brad Radke | Jesse Crain | Mike MacDougal | Joe Nathan | 713 | 615 | 98 |
| 2006-08-26 | vs MIN | 129 | L 7-8 | 76-53 | 3 | 38,636 | Jose Contreras | Johan Santana | Willie Eyre | Matt Thornton | | 720 | 623 | 97 |
| 2006-08-27 | vs MIN | 130 | W 6-1 | 77-53 | 2 | 35,193 | Mark Buehrle | Carlos Silva | Mark Buehrle | Carlos Silva | | 726 | 624 | 102 |
| 2006-08-29 | vs TBA | 131 | W 12-9 | 78-53 | 2 | 35,313 | Freddy Garcia | Casey Fossum | Freddy Garcia | Casey Fossum | Bobby Jenks | 738 | 633 | 105 |
| 2006-08-30 | vs TBA | 132 | W 5-4 | 79-53 | 2 | 35,539 | Jon Garland | Tim Corcoran | Jon Garland | Brian Meadows | Bobby Jenks | 743 | 637 | 106 |
| 2006-08-31 | vs TBA | 133 | L 3-5 | 79-54 | 2 | 33,178 | Javier Vazquez | Jason Hammel | Ruddy Lugo | Brandon McCarthy | Seth McClung | 746 | 642 | 104 |
| 2006-09-01 | @ KCA | 134 | L 5-7 | 79-55 | 2 | 15,501 | Jose Contreras | Runelvys Hernandez | Runelvys Hernandez | Jose Contreras | Joe Nelson | 751 | 649 | 102 |
| 2006-09-02 | @ KCA | 135 | W 5-3 | 80-55 | 2 | 18,028 | Mark Buehrle | Odalis Perez | Mark Buehrle | Odalis Perez | Bobby Jenks | 756 | 652 | 104 |
| 2006-09-03 | @ KCA | 136 | L 3-7 | 80-56 | 2 | 20,407 | Freddy Garcia | Mark Redman | Mark Redman | Freddy Garcia | | 759 | 659 | 100 |
| 2006-09-04 | @ BOS | 137 | L 2-3 | 80-57 | 2 | 36,206 | Jon Garland | Julian Tavarez | Mike Timlin | Brandon McCarthy | | 761 | 662 | 99 |
| 2006-09-05 | @ BOS | 138 | L 0-1 | 80-58 | 3 | 35,912 | Javier Vazquez | Kason Gabbard | Kason Gabbard | Javier Vazquez | Mike Timlin | 761 | 663 | 98 |
| 2006-09-06 | @ BOS | 139 | W 8-1 | 81-58 | 2 | 35,923 | Jose Contreras | Kyle Snyder | Jose Contreras | Kyle Snyder | | 769 | 664 | 105 |
| 2006-09-07 | vs CLE | 140 | L 1-9 | 81-59 | 2 | 34,671 | Mark Buehrle | Cliff Lee | Cliff Lee | Mark Buehrle | | 770 | 673 | 97 |
| 2006-09-08 | vs CLE | 141 | W 7-6 | 82-59 | 2 | 37,188 | Freddy Garcia | Paul Byrd | Matt Thornton | Tom Mastny | | 777 | 679 | 98 |
| 2006-09-09 | vs CLE | 142 | W 10-8 | 83-59 | 2 | 38,422 | Jon Garland | Fausto Carmona | Jon Garland | Fausto Carmona | Matt Thornton | 787 | 687 | 100 |
| 2006-09-10 | vs CLE | 143 | L 2-5 | 83-60 | 3 | 37,723 | Javier Vazquez | CC Sabathia | CC Sabathia | Brandon McCarthy | | 789 | 692 | 97 |
| 2006-09-11 | @ ANA | 144 | W 3-2 | 84-60 | 3 | 39,316 | Jose Contreras | John Lackey | Jose Contreras | John Lackey | Bobby Jenks | 792 | 694 | 98 |
| 2006-09-12 | @ ANA | 145 | L 3-4 | 84-61 | 3 | 39,304 | Mark Buehrle | Ervin Santana | Hector Carrasco | Bobby Jenks | | 795 | 698 | 97 |
| 2006-09-13 | @ ANA | 146 | W 9-0 | 85-61 | 3 | 37,030 | Freddy Garcia | Joe Saunders | Freddy Garcia | Joe Saunders | | 804 | 698 | 106 |
| 2006-09-15 | @ OAK | 147 | L 2-4 | 85-62 | 3 | 26,809 | Jon Garland | Esteban Loaiza | Esteban Loaiza | Jon Garland | Huston Street | 806 | 702 | 104 |
| 2006-09-16 | @ OAK | 148 | L 4-7 | 85-63 | 3 | 32,169 | Javier Vazquez | Barry Zito | Barry Zito | Matt Thornton | Huston Street | 810 | 709 | 101 |
| 2006-09-17 | @ OAK | 149 | L 4-5 | 85-64 | 3 | 28,806 | Jose Contreras | Joe Blanton | Joe Blanton | Jose Contreras | Justin Duchscherer | 814 | 714 | 100 |
| 2006-09-18 | vs DET | 150 | L 2-8 | 85-65 | 3 | 39,427 | Mark Buehrle | Kenny Rogers | Kenny Rogers | Mark Buehrle | | 816 | 722 | 94 |
| 2006-09-19 | vs DET | 151 | W 7-0 | 86-65 | 3 | 38,850 | Freddy Garcia | Justin Verlander | Freddy Garcia | Justin Verlander | | 823 | 722 | 101 |
| 2006-09-20 | vs DET | 152 | L 2-6 | 86-66 | 3 | 38,971 | Jon Garland | Jeremy Bonderman | Jeremy Bonderman | Jon Garland | | 825 | 728 | 97 |
| 2006-09-21 | vs SEA | 153 | L 0-9 | 86-67 | 3 | 33,976 | Javier Vazquez | Jake Woods | Jake Woods | Javier Vazquez | | 825 | 737 | 88 |
| 2006-09-22 | vs SEA | 154 | L 6-11 | 86-68 | 3 | 37,557 | Jose Contreras | Gil Meche | Emiliano Fruto | Jose Contreras | | 831 | 748 | 83 |
| 2006-09-23 | vs SEA | 155 | W 11-7 | 87-68 | 3 | 37,400 | Mark Buehrle | Felix Hernandez | Charlie Haeger | Joel Pineiro | | 842 | 755 | 87 |
| 2006-09-24 | vs SEA | 156 | W 12-7 | 88-68 | 3 | 37,518 | Freddy Garcia | Ryan Feierabend | Freddy Garcia | Ryan Feierabend | | 854 | 762 | 92 |
| 2006-09-25 | @ CLE | 157 | L 1-14 | 88-69 | 3 | 15,913 | Jon Garland | Cliff Lee | Cliff Lee | Jon Garland | | 855 | 776 | 79 |
| 2006-09-26 | @ CLE | 158 | L 0-6 | 88-70 | 3 | 16,080 | Javier Vazquez | CC Sabathia | CC Sabathia | Javier Vazquez | | 855 | 782 | 73 |
| 2006-09-27 | @ CLE | 159 | W 2-1 | 89-70 | 3 | 16,404 | Brandon McCarthy | Fausto Carmona | Brandon McCarthy | Fausto Carmona | Charlie Haeger | 857 | 783 | 74 |
| 2006-09-29 | @ MIN | 160 | W 4-3 | 90-70 | 3 | 45,439 | Freddy Garcia | Boof Bonser | Freddy Garcia | Boof Bonser | Bobby Jenks | 861 | 786 | 75 |
| 2006-09-30 | @ MIN | 161 | W 6-3 | 91-70 | 3 | 46,219 | Jon Garland | Matt Garza | Jon Garland | Matt Garza | | 867 | 789 | 78 |
| 2006-10-01 | @ MIN | 162 | L 1-5 | 91-71 | 3 | 45,182 | Javier Vazquez | Carlos Silva | Carlos Silva | Javier Vazquez | | 868 | 794 | 74 |