| 2006-04-04 | @ TOR | 1 | L 3-6 | 0-1 | 5 | 50,449 | Johan Santana | Roy Halladay | Roy Halladay | Johan Santana | B.J. Ryan | 3 | 6 | -3 |
| 2006-04-05 | @ TOR | 2 | W 13-4 | 1-1 | 3 | 18,156 | Brad Radke | Josh Towers | Brad Radke | Josh Towers | | 16 | 10 | 6 |
| 2006-04-06 | @ TOR | 3 | L 3-6 | 1-2 | 4 | 16,221 | Carlos Silva | Gustavo Chacin | Gustavo Chacin | Carlos Silva | B.J. Ryan | 19 | 16 | 3 |
| 2006-04-07 | @ CLE | 4 | L 6-11 | 1-3 | 5 | 42,445 | Kyle Lohse | Paul Byrd | Paul Byrd | Kyle Lohse | | 25 | 27 | -2 |
| 2006-04-08 | @ CLE | 5 | L 0-3 | 1-4 | 5 | 25,107 | Scott Baker | Jason Johnson | Jason Johnson | Scott Baker | Bob Wickman | 25 | 30 | -5 |
| 2006-04-09 | @ CLE | 6 | L 2-3 | 1-5 | 5 | 23,311 | Johan Santana | Jake Westbrook | Jake Westbrook | Johan Santana | Bob Wickman | 27 | 33 | -6 |
| 2006-04-11 | vs OAK | 7 | W 7-6 | 2-5 | 5 | 48,911 | Brad Radke | Dan Haren | Brad Radke | Dan Haren | Joe Nathan | 34 | 39 | -5 |
| 2006-04-12 | vs OAK | 8 | W 6-5 | 3-5 | 4 | 22,603 | Carlos Silva | Esteban Loaiza | Carlos Silva | Esteban Loaiza | Joe Nathan | 40 | 44 | -4 |
| 2006-04-13 | vs OAK | 9 | W 8-2 | 4-5 | 4 | 13,520 | Kyle Lohse | Joe Blanton | Kyle Lohse | Joe Blanton | | 48 | 46 | 2 |
| 2006-04-14 | vs NYA | 10 | W 5-1 | 5-5 | 4 | 30,622 | Scott Baker | Mike Mussina | Scott Baker | Mike Mussina | | 53 | 47 | 6 |
| 2006-04-15 | vs NYA | 11 | W 6-5 | 6-5 | 4 | 42,316 | Johan Santana | Jaret Wright | Juan Rincon | Mariano Rivera | | 59 | 52 | 7 |
| 2006-04-16 | vs NYA | 12 | L 3-9 | 6-6 | 4 | 22,627 | Brad Radke | Chien-Ming Wang | Chien-Ming Wang | Brad Radke | | 62 | 61 | 1 |
| 2006-04-18 | vs ANA | 13 | L 2-8 | 6-7 | 4 | 15,787 | Carlos Silva | Kelvim Escobar | Kelvim Escobar | Carlos Silva | Scot Shields | 64 | 69 | -5 |
| 2006-04-19 | vs ANA | 14 | W 12-10 | 7-7 | 4 | 21,507 | Kyle Lohse | Ervin Santana | Joe Nathan | J.C. Romero | | 76 | 79 | -3 |
| 2006-04-20 | vs ANA | 15 | L 4-6 | 7-8 | 4 | 12,990 | Scott Baker | Hector Carrasco | Kevin Gregg | Jesse Crain | Francisco Rodriguez | 80 | 85 | -5 |
| 2006-04-21 | @ CHA | 16 | L 1-7 | 7-9 | 4 | 31,287 | Johan Santana | Mark Buehrle | Mark Buehrle | Johan Santana | | 81 | 92 | -11 |
| 2006-04-22 | @ CHA | 17 | L 2-9 | 7-10 | 4 | 38,955 | Brad Radke | Freddy Garcia | Freddy Garcia | Brad Radke | | 83 | 101 | -18 |
| 2006-04-23 | @ CHA | 18 | L 3-7 | 7-11 | 4 | 38,102 | Carlos Silva | Jose Contreras | Jose Contreras | Carlos Silva | | 86 | 108 | -22 |
| 2006-04-25 | @ KCA | 19 | W 2-1 | 8-11 | 4 | 12,911 | Kyle Lohse | Scott Elarton | Francisco Liriano | Luke Hudson | Joe Nathan | 88 | 109 | -21 |
| 2006-04-26 | @ KCA | 20 | L 1-3 | 8-12 | 4 | 9,188 | Scott Baker | Runelvys Hernandez | Runelvys Hernandez | Scott Baker | Ambiorix Burgos | 89 | 112 | -23 |
| 2006-04-27 | @ KCA | 21 | W 7-3 | 9-12 | 4 | 11,391 | Johan Santana | Mark Redman | Johan Santana | Mark Redman | | 96 | 115 | -19 |
| 2006-04-28 | @ DET | 22 | L 0-9 | 9-13 | 4 | 23,263 | Brad Radke | Nate Robertson | Nate Robertson | Brad Radke | | 96 | 124 | -28 |
| 2006-04-29 | @ DET | 23 | L 1-18 | 9-14 | 4 | 24,258 | Carlos Silva | Justin Verlander | Justin Verlander | Carlos Silva | | 97 | 142 | -45 |
| 2006-04-30 | @ DET | 24 | L 0-6 | 9-15 | 4 | 24,323 | Kyle Lohse | Kenny Rogers | Kenny Rogers | Kyle Lohse | | 97 | 148 | -51 |
| 2006-05-01 | vs SEA | 25 | L 2-8 | 9-16 | 4 | 11,796 | Scott Baker | Joel Pineiro | Joel Pineiro | Scott Baker | | 99 | 156 | -57 |
| 2006-05-02 | vs SEA | 26 | W 5-1 | 10-16 | 4 | 14,513 | Johan Santana | Jarrod Washburn | Johan Santana | Jarrod Washburn | | 104 | 157 | -53 |
| 2006-05-03 | vs KCA | 27 | W 6-1 | 11-16 | 4 | 15,996 | Brad Radke | Joe Mays | Brad Radke | Joe Mays | | 110 | 158 | -48 |
| 2006-05-04 | vs KCA | 28 | L 0-1 | 11-17 | 4 | 11,803 | Carlos Silva | Jeremy Affeldt | Jeremy Affeldt | Carlos Silva | Ambiorix Burgos | 110 | 159 | -49 |
| 2006-05-05 | vs DET | 29 | L 6-9 | 11-18 | 4 | 23,892 | Kyle Lohse | Kenny Rogers | Kenny Rogers | Kyle Lohse | Todd Jones | 116 | 168 | -52 |
| 2006-05-06 | vs DET | 30 | W 7-6 | 12-18 | 4 | 20,907 | Scott Baker | Jeremy Bonderman | Juan Rincon | Todd Jones | | 123 | 174 | -51 |
| 2006-05-07 | vs DET | 31 | W 4-2 | 13-18 | 4 | 20,548 | Johan Santana | Mike Maroth | Johan Santana | Mike Maroth | Joe Nathan | 127 | 176 | -49 |
| 2006-05-08 | @ TEX | 32 | L 4-6 | 13-19 | 4 | 18,608 | Brad Radke | John Koronka | John Koronka | Brad Radke | Akinori Otsuka | 131 | 182 | -51 |
| 2006-05-09 | @ TEX | 33 | W 15-5 | 14-19 | 4 | 19,309 | Carlos Silva | Kevin Millwood | Carlos Silva | Kevin Millwood | Francisco Liriano | 146 | 187 | -41 |
| 2006-05-10 | @ TEX | 34 | W 4-3 | 15-19 | 4 | 23,037 | Kyle Lohse | Vicente Padilla | Kyle Lohse | Vicente Padilla | Joe Nathan | 150 | 190 | -40 |
| 2006-05-12 | vs CHA | 35 | W 10-1 | 16-19 | 4 | 30,473 | Johan Santana | Jon Garland | Johan Santana | Jon Garland | | 160 | 191 | -31 |
| 2006-05-13 | vs CHA | 36 | W 8-4 | 17-19 | 3 | 33,021 | Brad Radke | Javier Vazquez | Brad Radke | Javier Vazquez | | 168 | 195 | -27 |
| 2006-05-14 | vs CHA | 37 | L 7-9 | 17-20 | 3 | 21,796 | Carlos Silva | Mark Buehrle | Mark Buehrle | Carlos Silva | Bobby Jenks | 175 | 204 | -29 |
| 2006-05-15 | vs CHA | 38 | L 3-7 | 17-21 | 4 | 19,413 | Scott Baker | Freddy Garcia | Freddy Garcia | Scott Baker | | 178 | 211 | -33 |
| 2006-05-16 | @ DET | 39 | L 4-7 | 17-22 | 4 | 18,115 | Kyle Lohse | Nate Robertson | Nate Robertson | Kyle Lohse | Todd Jones | 182 | 218 | -36 |
| 2006-05-17 | @ DET | 40 | L 0-2 | 17-23 | 4 | 16,669 | Johan Santana | Justin Verlander | Justin Verlander | Johan Santana | Todd Jones | 182 | 220 | -38 |
| 2006-05-18 | @ DET | 41 | L 3-5 | 17-24 | 4 | 26,732 | Brad Radke | Kenny Rogers | Kenny Rogers | Brad Radke | Todd Jones | 185 | 225 | -40 |
| 2006-05-19 | @ MIL | 42 | W 7-1 | 18-24 | 4 | 28,462 | Francisco Liriano | Doug Davis | Francisco Liriano | Doug Davis | | 192 | 226 | -34 |
| 2006-05-20 | @ MIL | 43 | W 16-10 | 19-24 | 4 | 43,422 | Scott Baker | Ben Hendrickson | Scott Baker | Ben Hendrickson | | 208 | 236 | -28 |
| 2006-05-21 | @ MIL | 44 | L 3-5 | 19-25 | 4 | 35,180 | Boof Bonser | Chris Capuano | Chris Capuano | Jesse Crain | Derrick Turnbow | 211 | 241 | -30 |
| 2006-05-23 | vs CLE | 45 | W 6-5 | 20-25 | 4 | 19,334 | Johan Santana | Cliff Lee | Joe Nathan | Guillermo Mota | | 217 | 246 | -29 |
| 2006-05-24 | vs CLE | 46 | L 0-11 | 20-26 | 4 | 22,789 | Brad Radke | CC Sabathia | CC Sabathia | Brad Radke | | 217 | 257 | -40 |
| 2006-05-26 | vs SEA | 47 | W 3-1 | 21-26 | 4 | 28,082 | Francisco Liriano | Felix Hernandez | Francisco Liriano | Felix Hernandez | Joe Nathan | 220 | 258 | -38 |
| 2006-05-27 | vs SEA | 48 | W 9-5 | 22-26 | 4 | 25,305 | Boof Bonser | Jamie Moyer | Boof Bonser | Jamie Moyer | Juan Rincon | 229 | 263 | -34 |
| 2006-05-28 | vs SEA | 49 | W 4-3 | 23-26 | 4 | 24,388 | Johan Santana | Joel Pineiro | Joe Nathan | Eddie Guardado | | 233 | 266 | -33 |
| 2006-05-29 | @ ANA | 50 | L 3-4 | 23-27 | 4 | 40,007 | Brad Radke | John Lackey | Scot Shields | Jesse Crain | | 236 | 270 | -34 |
| 2006-05-30 | @ ANA | 51 | L 3-6 | 23-28 | 4 | 37,299 | Scott Baker | Jeff Weaver | Jeff Weaver | Scott Baker | Francisco Rodriguez | 239 | 276 | -37 |
| 2006-05-31 | @ ANA | 52 | W 7-1 | 24-28 | 4 | 44,001 | Francisco Liriano | Ervin Santana | Francisco Liriano | Ervin Santana | | 246 | 277 | -31 |
| 2006-06-01 | @ OAK | 53 | L 0-4 | 24-29 | 4 | 12,025 | Boof Bonser | Barry Zito | Barry Zito | Boof Bonser | | 246 | 281 | -35 |
| 2006-06-02 | @ OAK | 54 | W 2-1 | 25-29 | 4 | 16,138 | Johan Santana | Kirk Saarloos | Johan Santana | Kirk Saarloos | Joe Nathan | 248 | 282 | -34 |
| 2006-06-03 | @ OAK | 55 | L 1-2 | 25-30 | 4 | 23,194 | Brad Radke | Dan Haren | Brad Halsey | Brad Radke | Huston Street | 249 | 284 | -35 |
| 2006-06-04 | @ OAK | 56 | L 1-5 | 25-31 | 4 | 25,247 | Carlos Silva | Rich Harden | Brad Halsey | Carlos Silva | | 250 | 289 | -39 |
| 2006-06-06 | @ SEA | 57 | L 2-4 | 25-32 | 4 | 21,028 | Francisco Liriano | Felix Hernandez | Felix Hernandez | Francisco Liriano | J.J. Putz | 252 | 293 | -41 |
| 2006-06-07 | @ SEA | 58 | L 9-10 | 25-33 | 4 | 24,785 | Boof Bonser | Jamie Moyer | Julio Mateo | Jesse Crain | | 261 | 303 | -42 |
| 2006-06-08 | @ SEA | 59 | W 7-3 | 26-33 | 4 | 27,341 | Johan Santana | Joel Pineiro | Johan Santana | Joel Pineiro | | 268 | 306 | -38 |
| 2006-06-09 | vs BAL | 60 | W 7-5 | 27-33 | 4 | 22,894 | Brad Radke | Rodrigo Lopez | Joe Nathan | Bruce Chen | | 275 | 311 | -36 |
| 2006-06-10 | vs BAL | 61 | L 7-9 | 27-34 | 4 | 24,478 | Carlos Silva | Daniel Cabrera | Daniel Cabrera | Carlos Silva | | 282 | 320 | -38 |
| 2006-06-11 | vs BAL | 62 | W 4-0 | 28-34 | 4 | 25,438 | Francisco Liriano | Erik Bedard | Francisco Liriano | Erik Bedard | | 286 | 320 | -34 |
| 2006-06-13 | vs BOS | 63 | W 5-2 | 29-34 | 4 | 23,531 | Johan Santana | Curt Schilling | Dennys Reyes | Julian Tavarez | | 291 | 322 | -31 |
| 2006-06-14 | vs BOS | 64 | W 8-1 | 30-34 | 4 | 26,492 | Brad Radke | Matt Clement | Brad Radke | Matt Clement | | 299 | 323 | -24 |
| 2006-06-15 | vs BOS | 65 | W 5-3 | 31-34 | 4 | 21,191 | Carlos Silva | Tim Wakefield | Carlos Silva | Tim Wakefield | Joe Nathan | 304 | 326 | -22 |
| 2006-06-16 | @ PIT | 66 | W 4-2 | 32-34 | 3 | 33,025 | Francisco Liriano | Ian Snell | Francisco Liriano | Ian Snell | Joe Nathan | 308 | 328 | -20 |
| 2006-06-17 | @ PIT | 67 | W 5-3 | 33-34 | 3 | 34,085 | Boof Bonser | Paul Maholm | Jesse Crain | Damaso Marte | Joe Nathan | 313 | 331 | -18 |
| 2006-06-18 | @ PIT | 68 | W 8-2 | 34-34 | 3 | 25,104 | Johan Santana | Oliver Perez | Johan Santana | Oliver Perez | | 321 | 333 | -12 |
| 2006-06-20 | @ HOU | 69 | W 6-5 | 35-34 | 3 | 32,713 | Brad Radke | Roy Oswalt | Joe Nathan | Trever Miller | | 327 | 338 | -11 |
| 2006-06-21 | @ HOU | 70 | L 3-5 | 35-35 | 3 | 33,243 | Carlos Silva | Wandy Rodriguez | Dan Wheeler | Kyle Lohse | Brad Lidge | 330 | 343 | -13 |
| 2006-06-22 | @ HOU | 71 | W 4-2 | 36-35 | 3 | 43,769 | Francisco Liriano | Roger Clemens | Francisco Liriano | Roger Clemens | Joe Nathan | 334 | 345 | -11 |
| 2006-06-23 | vs CHN | 72 | W 7-2 | 37-35 | 3 | 34,361 | Johan Santana | Carlos Marmol | Johan Santana | Carlos Marmol | | 341 | 347 | -6 |
| 2006-06-24 | vs CHN | 73 | W 3-0 | 38-35 | 3 | 42,304 | Boof Bonser | Mark Prior | Boof Bonser | Mark Prior | Joe Nathan | 344 | 347 | -3 |
| 2006-06-25 | vs CHN | 74 | W 8-1 | 39-35 | 3 | 35,128 | Brad Radke | Sean Marshall | Brad Radke | Sean Marshall | | 352 | 348 | 4 |
| 2006-06-26 | vs LAN | 75 | W 8-2 | 40-35 | 3 | 22,528 | Carlos Silva | Chad Billingsley | Carlos Silva | Chad Billingsley | | 360 | 350 | 10 |
| 2006-06-27 | vs LAN | 76 | W 9-2 | 41-35 | 3 | 30,681 | Francisco Liriano | Derek Lowe | Francisco Liriano | Derek Lowe | | 369 | 352 | 17 |
| 2006-06-28 | vs LAN | 77 | W 6-3 | 42-35 | 3 | 34,157 | Johan Santana | Odalis Perez | Johan Santana | Odalis Perez | Joe Nathan | 375 | 355 | 20 |
| 2006-06-30 | vs MIL | 78 | W 8-2 | 43-35 | 3 | 28,412 | Brad Radke | Carlos Villanueva | Brad Radke | Carlos Villanueva | | 383 | 357 | 26 |
| 2006-07-01 | vs MIL | 79 | W 10-7 | 44-35 | 3 | 35,056 | Carlos Silva | Chris Capuano | Juan Rincon | Derrick Turnbow | Joe Nathan | 393 | 364 | 29 |
| 2006-07-02 | vs MIL | 80 | W 8-0 | 45-35 | 3 | 35,466 | Francisco Liriano | Zach Jackson | Francisco Liriano | Zach Jackson | | 401 | 364 | 37 |
| 2006-07-03 | @ KCA | 81 | W 6-5 | 46-35 | 3 | 28,401 | Johan Santana | Scott Elarton | Jesse Crain | Andy Sisco | Joe Nathan | 407 | 369 | 38 |
| 2006-07-04 | @ KCA | 82 | L 2-7 | 46-36 | 3 | 23,996 | Boof Bonser | Jimmy Gobble | Jimmy Gobble | Boof Bonser | Elmer Dessens | 409 | 376 | 33 |
| 2006-07-05 | @ KCA | 83 | L 3-6 | 46-37 | 3 | 12,085 | Brad Radke | Brandon Duckworth | Jeremy Affeldt | Jesse Crain | Ambiorix Burgos | 412 | 382 | 30 |
| 2006-07-07 | @ TEX | 84 | L 4-9 | 46-38 | 3 | 30,207 | Carlos Silva | John Wasdin | John Wasdin | Carlos Silva | | 416 | 391 | 25 |
| 2006-07-08 | @ TEX | 85 | W 4-0 | 47-38 | 3 | 36,035 | Francisco Liriano | John Rheinecker | Francisco Liriano | John Rheinecker | | 420 | 391 | 29 |
| 2006-07-09 | @ TEX | 86 | L 2-5 | 47-39 | 3 | 23,268 | Johan Santana | John Koronka | Rick Bauer | Johan Santana | Akinori Otsuka | 422 | 396 | 26 |
| 2006-07-13 | vs CLE | 87 | L 4-6 | 47-40 | 3 | 21,085 | Francisco Liriano | Cliff Lee | Cliff Lee | Francisco Liriano | Bob Wickman | 426 | 402 | 24 |
| 2006-07-14 | vs CLE | 88 | W 3-2 | 48-40 | 3 | 21,279 | Brad Radke | Paul Byrd | Joe Nathan | Edward Mujica | | 429 | 404 | 25 |
| 2006-07-15 | vs CLE | 89 | W 6-2 | 49-40 | 3 | 33,904 | Johan Santana | CC Sabathia | Johan Santana | CC Sabathia | | 435 | 406 | 29 |
| 2006-07-16 | vs CLE | 90 | W 5-2 | 50-40 | 3 | 31,838 | Carlos Silva | Jeremy Sowers | Carlos Silva | Jeremy Sowers | Joe Nathan | 440 | 408 | 32 |
| 2006-07-17 | vs TBA | 91 | W 6-3 | 51-40 | 3 | 17,071 | Scott Baker | Tim Corcoran | Scott Baker | Tim Corcoran | Joe Nathan | 446 | 411 | 35 |
| 2006-07-18 | vs TBA | 92 | W 8-1 | 52-40 | 3 | 22,808 | Francisco Liriano | Scott Kazmir | Francisco Liriano | Scott Kazmir | | 454 | 412 | 42 |
| 2006-07-19 | vs TBA | 93 | W 7-2 | 53-40 | 3 | 25,866 | Brad Radke | Jae Weong Seo | Brad Radke | Jae Weong Seo | | 461 | 414 | 47 |
| 2006-07-20 | vs TBA | 94 | W 6-4 | 54-40 | 3 | 25,104 | Johan Santana | James Shields | Johan Santana | James Shields | Joe Nathan | 467 | 418 | 49 |
| 2006-07-21 | @ CLE | 95 | W 14-6 | 55-40 | 3 | 29,695 | Carlos Silva | CC Sabathia | Dennys Reyes | CC Sabathia | | 481 | 424 | 57 |
| 2006-07-22 | @ CLE | 96 | L 0-11 | 55-41 | 3 | 26,895 | Scott Baker | Jeremy Sowers | Jeremy Sowers | Scott Baker | | 481 | 435 | 46 |
| 2006-07-23 | @ CLE | 97 | W 3-1 | 56-41 | 3 | 25,889 | Francisco Liriano | Jake Westbrook | Francisco Liriano | Jake Westbrook | Joe Nathan | 484 | 436 | 48 |
| 2006-07-24 | @ CHA | 98 | W 7-4 | 57-41 | 3 | 39,750 | Brad Radke | Javier Vazquez | Brad Radke | Javier Vazquez | | 491 | 440 | 51 |
| 2006-07-25 | @ CHA | 99 | W 4-3 | 58-41 | 3 | 36,984 | Johan Santana | Jose Contreras | Johan Santana | Jose Contreras | Joe Nathan | 495 | 443 | 52 |
| 2006-07-26 | @ CHA | 100 | W 7-4 | 59-41 | 3 | 39,387 | Carlos Silva | Mark Buehrle | Carlos Silva | Mark Buehrle | Joe Nathan | 502 | 447 | 55 |
| 2006-07-28 | vs DET | 101 | L 2-3 | 59-42 | 3 | 45,478 | Francisco Liriano | Zach Miner | Fernando Rodney | Juan Rincon | Todd Jones | 504 | 450 | 54 |
| 2006-07-29 | vs DET | 102 | L 6-8 | 59-43 | 3 | 45,496 | Brad Radke | Nate Robertson | Nate Robertson | Brad Radke | Todd Jones | 510 | 458 | 52 |
| 2006-07-30 | vs DET | 103 | W 6-4 | 60-43 | 3 | 43,204 | Johan Santana | Jeremy Bonderman | Pat Neshek | Jeremy Bonderman | Joe Nathan | 516 | 462 | 54 |
| 2006-07-31 | vs TEX | 104 | W 15-2 | 61-43 | 3 | 19,532 | Carlos Silva | John Rheinecker | Carlos Silva | John Rheinecker | | 531 | 464 | 67 |
| 2006-08-01 | vs TEX | 105 | L 0-9 | 61-44 | 3 | 25,969 | Scott Baker | Adam Eaton | Adam Eaton | Scott Baker | | 531 | 473 | 58 |
| 2006-08-02 | vs TEX | 106 | L 2-10 | 61-45 | 3 | 26,492 | Boof Bonser | Kip Wells | Kip Wells | Boof Bonser | | 533 | 483 | 50 |
| 2006-08-03 | @ KCA | 107 | W 8-2 | 62-45 | 3 | 12,022 | Brad Radke | Jorge de la Rosa | Brad Radke | Jorge de la Rosa | | 541 | 485 | 56 |
| 2006-08-04 | @ KCA | 108 | W 8-5 | 63-45 | 3 | 19,394 | Johan Santana | Mark Redman | Dennys Reyes | Scott Dohmann | Joe Nathan | 549 | 490 | 59 |
| 2006-08-05 | @ KCA | 109 | W 14-3 | 64-45 | 3 | 25,131 | Carlos Silva | Runelvys Hernandez | Carlos Silva | Runelvys Hernandez | | 563 | 493 | 70 |
| 2006-08-06 | @ KCA | 110 | W 11-5 | 65-45 | 3 | 14,064 | Michael Smith | Odalis Perez | Dennys Reyes | Todd Wellemeyer | | 574 | 498 | 76 |
| 2006-08-07 | @ DET | 111 | L 3-9 | 65-46 | 3 | 34,870 | Francisco Liriano | Zach Miner | Zach Miner | Francisco Liriano | | 577 | 507 | 70 |
| 2006-08-08 | @ DET | 112 | W 4-2 | 66-46 | 3 | 35,624 | Brad Radke | Nate Robertson | Brad Radke | Nate Robertson | Joe Nathan | 581 | 509 | 72 |
| 2006-08-09 | @ DET | 113 | W 4-3 | 67-46 | 3 | 36,339 | Johan Santana | Jeremy Bonderman | Johan Santana | Joel Zumaya | Joe Nathan | 585 | 512 | 73 |
| 2006-08-10 | vs TOR | 114 | L 0-5 | 67-47 | 3 | 30,118 | Carlos Silva | Ted Lilly | Ted Lilly | Carlos Silva | | 585 | 517 | 68 |
| 2006-08-11 | vs TOR | 115 | L 1-7 | 67-48 | 3 | 31,814 | Matt Garza | A.J. Burnett | A.J. Burnett | Matt Garza | | 586 | 524 | 62 |
| 2006-08-12 | vs TOR | 116 | L 0-4 | 67-49 | 3 | 36,261 | Boof Bonser | Scott Downs | Scott Downs | Boof Bonser | | 586 | 528 | 58 |
| 2006-08-13 | vs TOR | 117 | W 5-0 | 68-49 | 3 | 32,811 | Brad Radke | Shaun Marcum | Brad Radke | Shaun Marcum | | 591 | 528 | 63 |
| 2006-08-15 | vs CLE | 118 | W 4-1 | 69-49 | 3 | 34,854 | Johan Santana | Jake Westbrook | Johan Santana | Jake Westbrook | | 595 | 529 | 66 |
| 2006-08-16 | vs CLE | 119 | W 7-2 | 70-49 | 3 | 42,328 | Carlos Silva | Cliff Lee | Pat Neshek | Fausto Carmona | | 602 | 531 | 71 |
| 2006-08-17 | vs CLE | 120 | L 2-3 | 70-50 | 3 | 27,664 | Matt Garza | Paul Byrd | Paul Byrd | Matt Garza | | 604 | 534 | 70 |
| 2006-08-18 | vs CHA | 121 | W 7-3 | 71-50 | 3 | 43,204 | Boof Bonser | Freddy Garcia | Pat Neshek | Freddy Garcia | | 611 | 537 | 74 |
| 2006-08-19 | vs CHA | 122 | L 1-4 | 71-51 | 3 | 46,215 | Brad Radke | Jon Garland | Jon Garland | Brad Radke | Bobby Jenks | 612 | 541 | 71 |
| 2006-08-20 | vs CHA | 123 | W 7-3 | 72-51 | 3 | 42,537 | Johan Santana | Javier Vazquez | Johan Santana | Javier Vazquez | | 619 | 544 | 75 |
| 2006-08-22 | @ BAL | 124 | L 3-6 | 72-52 | 3 | 19,756 | Carlos Silva | Adam Loewen | Adam Loewen | Carlos Silva | Chris Ray | 622 | 550 | 72 |
| 2006-08-23 | @ BAL | 125 | W 4-1 | 73-52 | 3 | 19,258 | Matt Garza | Rodrigo Lopez | Matt Garza | Rodrigo Lopez | Joe Nathan | 626 | 551 | 75 |
| 2006-08-24 | @ BAL | 126 | W 11-2 | 74-52 | 3 | 24,848 | Boof Bonser | Kris Benson | Boof Bonser | Kris Benson | | 637 | 553 | 84 |
| 2006-08-25 | @ CHA | 127 | W 5-4 | 75-52 | 3 | 35,931 | Brad Radke | Javier Vazquez | Jesse Crain | Mike MacDougal | Joe Nathan | 642 | 557 | 85 |
| 2006-08-26 | @ CHA | 128 | W 8-7 | 76-52 | 2 | 38,636 | Johan Santana | Jose Contreras | Willie Eyre | Matt Thornton | | 650 | 564 | 86 |
| 2006-08-27 | @ CHA | 129 | L 1-6 | 76-53 | 3 | 35,193 | Carlos Silva | Mark Buehrle | Mark Buehrle | Carlos Silva | | 651 | 570 | 81 |
| 2006-08-29 | vs KCA | 130 | L 0-2 | 76-54 | 3 | 24,904 | Matt Garza | Mark Redman | Mark Redman | Matt Garza | | 651 | 572 | 79 |
| 2006-08-30 | vs KCA | 131 | L 3-4 | 76-55 | 3 | 28,668 | Boof Bonser | Luke Hudson | Luke Hudson | Boof Bonser | Joe Nelson | 654 | 576 | 78 |
| 2006-08-31 | vs KCA | 132 | W 3-1 | 77-55 | 3 | 21,287 | Johan Santana | Jorge de la Rosa | Johan Santana | Jorge de la Rosa | Joe Nathan | 657 | 577 | 80 |
| 2006-09-01 | @ NYA | 133 | L 1-8 | 77-56 | 3 | 54,311 | Carlos Silva | Cory Lidle | Cory Lidle | Carlos Silva | | 658 | 585 | 73 |
| 2006-09-02 | @ NYA | 134 | W 6-1 | 78-56 | 3 | 53,220 | Scott Baker | Jeff Karstens | Scott Baker | Jeff Karstens | Jesse Crain | 664 | 586 | 78 |
| 2006-09-03 | @ NYA | 135 | L 1-10 | 78-57 | 3 | 55,155 | Matt Garza | Darrell Rasner | Darrell Rasner | Matt Garza | | 665 | 596 | 69 |
| 2006-09-04 | @ TBA | 136 | W 2-1 | 79-57 | 3 | 15,910 | Boof Bonser | Tim Corcoran | Boof Bonser | Tim Corcoran | Joe Nathan | 667 | 597 | 70 |
| 2006-09-05 | @ TBA | 137 | W 8-0 | 80-57 | 2 | 8,256 | Johan Santana | Jae Weong Seo | Johan Santana | Jae Weong Seo | | 675 | 597 | 78 |
| 2006-09-06 | @ TBA | 138 | L 2-4 | 80-58 | 3 | 8,942 | Carlos Silva | Jason Hammel | Shawn Camp | Pat Neshek | Seth McClung | 677 | 601 | 76 |
| 2006-09-07 | vs DET | 139 | L 2-7 | 80-59 | 3 | 21,229 | Scott Baker | Justin Verlander | Justin Verlander | Scott Baker | | 679 | 608 | 71 |
| 2006-09-08 | vs DET | 140 | W 9-5 | 81-59 | 3 | 29,042 | Matt Garza | Wil Ledezma | Pat Neshek | Wil Ledezma | | 688 | 613 | 75 |
| 2006-09-09 | vs DET | 141 | W 2-1 | 82-59 | 3 | 39,160 | Boof Bonser | Nate Robertson | Boof Bonser | Nate Robertson | Joe Nathan | 690 | 614 | 76 |
| 2006-09-10 | vs DET | 142 | W 12-1 | 83-59 | 2 | 40,158 | Johan Santana | Jeremy Bonderman | Johan Santana | Jeremy Bonderman | | 702 | 615 | 87 |
| 2006-09-11 | vs OAK | 143 | W 9-4 | 84-59 | 2 | 15,728 | Carlos Silva | Joe Blanton | Carlos Silva | Joe Blanton | Joe Nathan | 711 | 619 | 92 |
| 2006-09-12 | vs OAK | 144 | W 7-5 | 85-59 | 2 | 20,991 | Matt Guerrier | Kirk Saarloos | Dennys Reyes | Joe Kennedy | Joe Nathan | 718 | 624 | 94 |
| 2006-09-13 | vs OAK | 145 | L 0-1 | 85-60 | 2 | 18,902 | Francisco Liriano | Dan Haren | Dan Haren | Matt Garza | Huston Street | 718 | 625 | 93 |
| 2006-09-14 | @ CLE | 146 | W 9-4 | 86-60 | 2 | 21,424 | Boof Bonser | Cliff Lee | Jesse Crain | Jason Davis | | 727 | 629 | 98 |
| 2006-09-15 | @ CLE | 147 | L 4-5 | 86-61 | 2 | 32,473 | Johan Santana | Fausto Carmona | Fernando Cabrera | Pat Neshek | | 731 | 634 | 97 |
| 2006-09-16 | @ CLE | 148 | W 4-1 | 87-61 | 2 | 26,757 | Carlos Silva | CC Sabathia | Carlos Silva | CC Sabathia | Joe Nathan | 735 | 635 | 100 |
| 2006-09-17 | @ CLE | 149 | W 6-1 | 88-61 | 2 | 20,324 | Scott Baker | Paul Byrd | Scott Baker | Paul Byrd | Matt Guerrier | 741 | 636 | 105 |
| 2006-09-19 | @ BOS | 150 | W 7-3 | 89-61 | 2 | 36,242 | Matt Garza | Tim Wakefield | Matt Garza | Tim Wakefield | | 748 | 639 | 109 |
| 2006-09-20 | @ BOS | 151 | W 8-2 | 90-61 | 2 | 36,484 | Boof Bonser | Curt Schilling | Boof Bonser | Craig Hansen | | 756 | 641 | 115 |
| 2006-09-21 | @ BOS | 152 | L 0-6 | 90-62 | 2 | 36,434 | Johan Santana | Josh Beckett | Josh Beckett | Johan Santana | | 756 | 647 | 109 |
| 2006-09-22 | @ BAL | 153 | L 3-7 | 90-63 | 2 | 21,051 | Carlos Silva | Daniel Cabrera | Daniel Cabrera | Carlos Silva | | 759 | 654 | 105 |
| 2006-09-23 | @ BAL | 154 | W 8-5 | 91-63 | 2 | 21,980 | Scott Baker | Erik Bedard | Matt Guerrier | Erik Bedard | Joe Nathan | 767 | 659 | 108 |
| 2006-09-24 | @ BAL | 155 | W 6-3 | 92-63 | 2 | 23,005 | Matt Garza | Adam Loewen | Matt Garza | Adam Loewen | Joe Nathan | 773 | 662 | 111 |
| 2006-09-25 | vs KCA | 156 | W 8-1 | 93-63 | 2 | 18,108 | Boof Bonser | Jorge de la Rosa | Boof Bonser | Jorge de la Rosa | | 781 | 663 | 118 |
| 2006-09-26 | vs KCA | 157 | W 3-2 | 94-63 | 2 | 24,819 | Johan Santana | Odalis Perez | Johan Santana | Joel Peralta | Joe Nathan | 784 | 665 | 119 |
| 2006-09-27 | vs KCA | 158 | L 4-6 | 94-64 | 2 | 28,540 | Carlos Silva | Mark Redman | Mark Redman | Carlos Silva | Joe Nelson | 788 | 671 | 117 |
| 2006-09-28 | vs KCA | 159 | W 2-1 | 95-64 | 2 | 26,654 | Brad Radke | Luke Hudson | Joe Nathan | Scott Dohmann | | 790 | 672 | 118 |
| 2006-09-29 | vs CHA | 160 | L 3-4 | 95-65 | 2 | 45,439 | Boof Bonser | Freddy Garcia | Freddy Garcia | Boof Bonser | Bobby Jenks | 793 | 676 | 117 |
| 2006-09-30 | vs CHA | 161 | L 3-6 | 95-66 | 2 | 46,219 | Matt Garza | Jon Garland | Jon Garland | Matt Garza | | 796 | 682 | 114 |
| 2006-10-01 | vs CHA | 162 | W 5-1 | 96-66 | 1 | 45,182 | Carlos Silva | Javier Vazquez | Carlos Silva | Javier Vazquez | | 801 | 683 | 118 |