| 2006-04-03 | @ BAL | 1 | L 6-9 | 0-1 | 4 | 46,986 | Scott Kazmir | Rodrigo Lopez | Rodrigo Lopez | Scott Kazmir | Chris Ray | 6 | 9 | -3 |
| 2006-04-05 | @ BAL | 2 | L 6-16 | 0-2 | 5 | 16,083 | Seth McClung | Erik Bedard | Erik Bedard | Seth McClung | | 12 | 25 | -13 |
| 2006-04-06 | @ BAL | 3 | W 2-0 | 1-2 | 5 | 13,194 | Mark Hendrickson | Kris Benson | Mark Hendrickson | Kris Benson | | 14 | 25 | -11 |
| 2006-04-07 | @ TOR | 4 | W 9-8 | 2-2 | 3 | 15,631 | Casey Fossum | Scott Downs | Scott Dunn | Pete Walker | Dan Miceli | 23 | 33 | -10 |
| 2006-04-08 | @ TOR | 5 | L 4-8 | 2-3 | 4 | 18,755 | Doug Waechter | Ted Lilly | Brian Tallet | Jason Childers | | 27 | 41 | -14 |
| 2006-04-09 | @ TOR | 6 | W 5-2 | 3-3 | 2 | 20,184 | Scott Kazmir | Roy Halladay | Scott Kazmir | Roy Halladay | Dan Miceli | 32 | 43 | -11 |
| 2006-04-10 | vs BAL | 7 | L 3-6 | 3-4 | 4 | 40,199 | Seth McClung | Erik Bedard | Erik Bedard | Seth McClung | Chris Ray | 35 | 49 | -14 |
| 2006-04-11 | vs BAL | 8 | L 4-8 | 3-5 | 5 | 12,600 | Jason Hammel | Kris Benson | Kris Benson | Jason Hammel | Chris Ray | 39 | 57 | -18 |
| 2006-04-12 | vs BAL | 9 | W 7-4 | 4-5 | 5 | 10,707 | Casey Fossum | Daniel Cabrera | Shawn Camp | Sendy Rleal | Dan Miceli | 46 | 61 | -15 |
| 2006-04-13 | vs BAL | 10 | L 5-6 | 4-6 | 5 | 13,042 | Doug Waechter | Bruce Chen | Chris Ray | Dan Miceli | | 51 | 67 | -16 |
| 2006-04-14 | vs KCA | 11 | W 7-2 | 5-6 | 5 | 12,092 | Scott Kazmir | Scott Elarton | Travis Harper | Scott Elarton | | 58 | 69 | -11 |
| 2006-04-15 | vs KCA | 12 | W 6-3 | 6-6 | 4 | 20,002 | Seth McClung | Mike Wood | Seth McClung | Luke Hudson | Shawn Camp | 64 | 72 | -8 |
| 2006-04-16 | vs KCA | 13 | W 9-5 | 7-6 | 3 | 11,853 | Jason Hammel | Mark Redman | Brian Meadows | Steve Stemle | | 73 | 77 | -4 |
| 2006-04-18 | @ BOS | 14 | L 4-7 | 7-7 | 4 | 36,423 | Casey Fossum | Matt Clement | Mike Timlin | Ruddy Lugo | Jonathan Papelbon | 77 | 84 | -7 |
| 2006-04-19 | @ BOS | 15 | L 1-9 | 7-8 | 5 | 36,454 | Doug Waechter | Curt Schilling | Curt Schilling | Doug Waechter | | 78 | 93 | -15 |
| 2006-04-20 | @ BOS | 16 | W 5-1 | 8-8 | 4 | 36,607 | Scott Kazmir | Tim Wakefield | Scott Kazmir | Tim Wakefield | Dan Miceli | 83 | 94 | -11 |
| 2006-04-21 | @ TEX | 17 | L 7-13 | 8-9 | 4 | 25,129 | Seth McClung | Kameron Loe | C.J. Wilson | Seth McClung | | 90 | 107 | -17 |
| 2006-04-22 | @ TEX | 18 | L 5-6 | 8-10 | 5 | 35,302 | Edwin Jackson | John Rheinecker | Francisco Cordero | Chad Orvella | | 95 | 113 | -18 |
| 2006-04-23 | @ TEX | 19 | L 3-8 | 8-11 | 5 | 29,232 | Casey Fossum | John Koronka | John Koronka | Casey Fossum | | 98 | 121 | -23 |
| 2006-04-25 | @ NYA | 20 | L 1-9 | 8-12 | 5 | 36,334 | Scott Kazmir | Mike Mussina | Mike Mussina | Scott Kazmir | | 99 | 130 | -31 |
| 2006-04-26 | @ NYA | 21 | W 4-2 | 9-12 | 5 | 35,642 | Seth McClung | Chien-Ming Wang | Chad Orvella | Mariano Rivera | Shawn Camp | 103 | 132 | -29 |
| 2006-04-27 | @ NYA | 22 | L 1-4 | 9-13 | 5 | 45,826 | Mark Hendrickson | Shawn Chacon | Shawn Chacon | Mark Hendrickson | Mariano Rivera | 104 | 136 | -32 |
| 2006-04-28 | vs BOS | 23 | W 5-2 | 10-13 | 5 | 22,565 | Casey Fossum | Matt Clement | Casey Fossum | Matt Clement | Tyler Walker | 109 | 138 | -29 |
| 2006-04-29 | vs BOS | 24 | L 6-9 | 10-14 | 5 | 27,415 | Doug Waechter | Lenny DiNardo | Keith Foulke | Tyler Walker | Jonathan Papelbon | 115 | 147 | -32 |
| 2006-04-30 | vs BOS | 25 | W 5-4 | 11-14 | 5 | 26,690 | Scott Kazmir | Curt Schilling | Scott Kazmir | Curt Schilling | Shawn Camp | 120 | 151 | -31 |
| 2006-05-01 | vs TEX | 26 | L 0-3 | 11-15 | 5 | 7,295 | Seth McClung | Kameron Loe | Kameron Loe | Seth McClung | Akinori Otsuka | 120 | 154 | -34 |
| 2006-05-02 | vs TEX | 27 | L 5-7 | 11-16 | 5 | 7,147 | Mark Hendrickson | Rob Tejeda | Rob Tejeda | Mark Hendrickson | Akinori Otsuka | 125 | 161 | -36 |
| 2006-05-03 | vs NYA | 28 | L 2-4 | 11-17 | 5 | 17,059 | Casey Fossum | Jaret Wright | Kyle Farnsworth | Tyler Walker | Mariano Rivera | 127 | 165 | -38 |
| 2006-05-04 | vs NYA | 29 | L 5-10 | 11-18 | 5 | 22,164 | Doug Waechter | Randy Johnson | Randy Johnson | Chad Orvella | | 132 | 175 | -43 |
| 2006-05-05 | @ OAK | 30 | W 3-1 | 12-18 | 5 | 12,552 | Scott Kazmir | Joe Blanton | Scott Kazmir | Joe Blanton | Tyler Walker | 135 | 176 | -41 |
| 2006-05-06 | @ OAK | 31 | L 2-3 | 12-19 | 5 | 25,080 | Seth McClung | Barry Zito | Joe Kennedy | Chad Orvella | | 137 | 179 | -42 |
| 2006-05-07 | @ OAK | 32 | W 3-2 | 13-19 | 5 | 22,837 | Mark Hendrickson | Brad Halsey | Mark Hendrickson | Brad Halsey | Tyler Walker | 140 | 181 | -41 |
| 2006-05-08 | @ SEA | 33 | L 3-6 | 13-20 | 5 | 16,102 | Casey Fossum | Gil Meche | Gil Meche | Chad Orvella | J.J. Putz | 143 | 187 | -44 |
| 2006-05-09 | @ SEA | 34 | L 1-8 | 13-21 | 5 | 19,726 | Doug Waechter | Felix Hernandez | Felix Hernandez | Doug Waechter | Rafael Soriano | 144 | 195 | -51 |
| 2006-05-10 | @ SEA | 35 | W 1-0 | 14-21 | 5 | 21,801 | Scott Kazmir | Jamie Moyer | Scott Kazmir | Jamie Moyer | Tyler Walker | 145 | 195 | -50 |
| 2006-05-12 | vs TOR | 36 | W 4-1 | 15-21 | 5 | 11,816 | Seth McClung | Casey Janssen | Seth McClung | Casey Janssen | Tyler Walker | 149 | 196 | -47 |
| 2006-05-13 | vs TOR | 37 | L 1-8 | 15-22 | 5 | 15,184 | Mark Hendrickson | Roy Halladay | Roy Halladay | Mark Hendrickson | | 150 | 204 | -54 |
| 2006-05-14 | vs TOR | 38 | L 3-8 | 15-23 | 5 | 12,224 | Casey Fossum | Josh Towers | Josh Towers | Casey Fossum | | 153 | 212 | -59 |
| 2006-05-16 | vs CHA | 39 | W 10-7 | 16-23 | 5 | 11,566 | Scott Kazmir | Brandon McCarthy | Scott Kazmir | Brandon McCarthy | Tyler Walker | 163 | 219 | -56 |
| 2006-05-17 | vs CHA | 40 | L 2-5 | 16-24 | 5 | 11,607 | Seth McClung | Jon Garland | Jon Garland | Ruddy Lugo | Bobby Jenks | 165 | 224 | -59 |
| 2006-05-18 | vs CHA | 41 | W 5-4 | 17-24 | 5 | 22,665 | Mark Hendrickson | Javier Vazquez | Mark Hendrickson | Javier Vazquez | Tyler Walker | 170 | 228 | -58 |
| 2006-05-19 | vs FLO | 42 | W 5-4 | 18-24 | 5 | 10,017 | Casey Fossum | Brian Moehler | Tyler Walker | Yusmeiro Petit | | 175 | 232 | -57 |
| 2006-05-20 | vs FLO | 43 | W 4-3 | 19-24 | 5 | 14,837 | Doug Waechter | Josh Johnson | Ruddy Lugo | Logan Kensing | | 179 | 235 | -56 |
| 2006-05-21 | vs FLO | 44 | W 3-0 | 20-24 | 5 | 19,058 | Scott Kazmir | Dontrelle Willis | Scott Kazmir | Dontrelle Willis | Tyler Walker | 182 | 235 | -53 |
| 2006-05-22 | @ TOR | 45 | L 4-6 | 20-25 | 5 | 22,563 | Seth McClung | Casey Janssen | Casey Janssen | Seth McClung | B.J. Ryan | 186 | 241 | -55 |
| 2006-05-23 | @ TOR | 46 | L 1-4 | 20-26 | 5 | 34,594 | Mark Hendrickson | Roy Halladay | Roy Halladay | Mark Hendrickson | B.J. Ryan | 187 | 245 | -58 |
| 2006-05-24 | @ TOR | 47 | W 10-8 | 21-26 | 5 | 20,187 | Casey Fossum | Josh Towers | Shawn Camp | Jason Frasor | Tyler Walker | 197 | 253 | -56 |
| 2006-05-25 | @ BOS | 48 | L 1-4 | 21-27 | 5 | 36,209 | Doug Waechter | Josh Beckett | Josh Beckett | Doug Waechter | Jonathan Papelbon | 198 | 257 | -59 |
| 2006-05-26 | @ BOS | 49 | L 4-8 | 21-28 | 5 | 36,129 | Scott Kazmir | David Wells | Julian Tavarez | Scott Kazmir | Jonathan Papelbon | 202 | 265 | -63 |
| 2006-05-27 | @ BOS | 50 | L 4-6 | 21-29 | 5 | 36,409 | Seth McClung | Curt Schilling | Curt Schilling | Seth McClung | Jonathan Papelbon | 206 | 271 | -65 |
| 2006-05-28 | @ BOS | 51 | L 4-5 | 21-30 | 5 | 36,015 | Mark Hendrickson | Tim Wakefield | Tim Wakefield | Mark Hendrickson | Julian Tavarez | 210 | 276 | -66 |
| 2006-05-30 | @ BAL | 52 | L 5-7 | 21-31 | 5 | 15,505 | Doug Waechter | Rodrigo Lopez | Rodrigo Lopez | Doug Waechter | Chris Ray | 215 | 283 | -68 |
| 2006-05-31 | @ BAL | 53 | L 5-6 | 21-32 | 5 | 16,134 | James Shields | Bruce Chen | Sendy Rleal | Tyler Walker | | 220 | 289 | -69 |
| 2006-06-01 | @ BAL | 54 | W 8-6 | 22-32 | 5 | 14,044 | Scott Kazmir | Erik Bedard | Travis Harper | Erik Bedard | | 228 | 295 | -67 |
| 2006-06-02 | vs TOR | 55 | L 4-13 | 22-33 | 5 | 9,463 | Seth McClung | Casey Janssen | Casey Janssen | Seth McClung | | 232 | 308 | -76 |
| 2006-06-03 | vs TOR | 56 | L 2-6 | 22-34 | 5 | 15,696 | Mark Hendrickson | Roy Halladay | Roy Halladay | Mark Hendrickson | B.J. Ryan | 234 | 314 | -80 |
| 2006-06-04 | vs TOR | 57 | W 10-5 | 23-34 | 5 | 14,347 | Doug Waechter | Gustavo Chacin | Doug Waechter | Gustavo Chacin | | 244 | 319 | -75 |
| 2006-06-05 | vs ANA | 58 | W 4-0 | 24-34 | 5 | 9,519 | James Shields | Jeff Weaver | James Shields | Jeff Weaver | Tyler Walker | 248 | 319 | -71 |
| 2006-06-06 | vs ANA | 59 | L 2-12 | 24-35 | 5 | 13,762 | Scott Kazmir | Ervin Santana | Ervin Santana | Scott Kazmir | | 250 | 331 | -81 |
| 2006-06-07 | vs ANA | 60 | L 2-6 | 24-36 | 5 | 9,517 | Seth McClung | Jered Weaver | Jered Weaver | Seth McClung | | 252 | 337 | -85 |
| 2006-06-09 | @ KCA | 61 | L 2-4 | 24-37 | 5 | 26,508 | Mark Hendrickson | Mark Redman | Mark Redman | Mark Hendrickson | Ambiorix Burgos | 254 | 341 | -87 |
| 2006-06-10 | @ KCA | 62 | W 9-5 | 25-37 | 5 | 12,929 | Casey Fossum | Mike Wood | Casey Fossum | Mike Wood | | 263 | 346 | -83 |
| 2006-06-11 | @ KCA | 63 | W 8-2 | 26-37 | 5 | 17,792 | James Shields | Scott Elarton | James Shields | Scott Elarton | | 271 | 348 | -77 |
| 2006-06-12 | @ DET | 64 | L 3-4 | 26-38 | 5 | 16,302 | Scott Kazmir | Justin Verlander | Todd Jones | Brian Meadows | | 274 | 352 | -78 |
| 2006-06-13 | @ DET | 65 | L 1-7 | 26-39 | 5 | 20,935 | Seth McClung | Kenny Rogers | Kenny Rogers | Seth McClung | | 275 | 359 | -84 |
| 2006-06-14 | @ DET | 66 | W 5-1 | 27-39 | 5 | 25,265 | Mark Hendrickson | Jeremy Bonderman | Brian Meadows | Todd Jones | | 280 | 360 | -80 |
| 2006-06-15 | @ DET | 67 | L 2-6 | 27-40 | 5 | 28,269 | Casey Fossum | Zach Miner | Zach Miner | Casey Fossum | | 282 | 366 | -84 |
| 2006-06-16 | @ PHI | 68 | W 10-4 | 28-40 | 5 | 31,042 | James Shields | Cole Hamels | James Shields | Cole Hamels | | 292 | 370 | -78 |
| 2006-06-17 | @ PHI | 69 | W 7-2 | 29-40 | 5 | 35,939 | Scott Kazmir | Scott Mathieson | Scott Kazmir | Scott Mathieson | | 299 | 372 | -73 |
| 2006-06-18 | @ PHI | 70 | L 5-8 | 29-41 | 5 | 42,658 | Seth McClung | Ryan Madson | Ryan Madson | Seth McClung | Tom Gordon | 304 | 380 | -76 |
| 2006-06-20 | vs ARI | 71 | W 8-5 | 30-41 | 5 | 10,430 | Mark Hendrickson | Miguel Batista | Mark Hendrickson | Miguel Batista | | 312 | 385 | -73 |
| 2006-06-21 | vs ARI | 72 | W 3-2 | 31-41 | 5 | 17,182 | James Shields | Brandon Webb | James Shields | Brandon Webb | Brian Meadows | 315 | 387 | -72 |
| 2006-06-22 | vs ARI | 73 | W 4-1 | 32-41 | 5 | 17,888 | Scott Kazmir | Edgar Gonzalez | Scott Kazmir | Edgar Gonzalez | Brian Meadows | 319 | 388 | -69 |
| 2006-06-23 | vs ATL | 74 | L 3-4 | 32-42 | 5 | 21,280 | Casey Fossum | John Smoltz | Jorge Sosa | Chad Harville | | 322 | 392 | -70 |
| 2006-06-24 | vs ATL | 75 | W 3-2 | 33-42 | 5 | 26,686 | Tim Corcoran | Lance Cormier | Tim Corcoran | Lance Cormier | Chad Harville | 325 | 394 | -69 |
| 2006-06-25 | vs ATL | 76 | L 1-4 | 33-43 | 5 | 20,556 | Mark Hendrickson | Chuck James | Chuck James | Mark Hendrickson | Jorge Sosa | 326 | 398 | -72 |
| 2006-06-26 | @ FLO | 77 | L 5-8 | 33-44 | 5 | 7,416 | James Shields | Josh Johnson | Josh Johnson | James Shields | Joe Borowski | 331 | 406 | -75 |
| 2006-06-27 | @ FLO | 78 | L 4-8 | 33-45 | 5 | 8,418 | Scott Kazmir | Ricky Nolasco | Ricky Nolasco | Scott Kazmir | | 335 | 414 | -79 |
| 2006-06-28 | @ FLO | 79 | W 3-1 | 34-45 | 5 | 10,367 | Casey Fossum | Scott Olsen | Casey Fossum | Scott Olsen | Brian Meadows | 338 | 415 | -77 |
| 2006-06-30 | @ WAS | 80 | W 11-1 | 35-45 | 5 | 21,854 | Tim Corcoran | Mike O'Connor | Tim Corcoran | Mike O'Connor | | 349 | 416 | -67 |
| 2006-07-01 | @ WAS | 81 | L 3-4 | 35-46 | 5 | 21,515 | James Shields | Livan Hernandez | Chad Cordero | Brian Meadows | | 352 | 420 | -68 |
| 2006-07-02 | @ WAS | 82 | L 2-6 | 35-47 | 5 | 23,823 | Jae Weong Seo | Ramon Ortiz | Ramon Ortiz | Jae Weong Seo | | 354 | 426 | -72 |
| 2006-07-03 | vs BOS | 83 | W 3-0 | 36-47 | 5 | 26,149 | Scott Kazmir | Josh Beckett | Scott Kazmir | Josh Beckett | | 357 | 426 | -69 |
| 2006-07-04 | vs BOS | 84 | W 9-6 | 37-47 | 5 | 21,186 | Casey Fossum | Curt Schilling | Jon Switzer | Curt Schilling | Shawn Camp | 366 | 432 | -66 |
| 2006-07-05 | vs BOS | 85 | W 5-2 | 38-47 | 5 | 15,001 | Tim Corcoran | Jason Johnson | Tim Corcoran | Jason Johnson | Brian Meadows | 371 | 434 | -63 |
| 2006-07-06 | vs BOS | 86 | L 5-12 | 38-48 | 5 | 19,330 | James Shields | Tim Wakefield | Tim Wakefield | James Shields | | 376 | 446 | -70 |
| 2006-07-07 | vs NYA | 87 | L 0-1 | 38-49 | 5 | 25,584 | Jae Weong Seo | Jaret Wright | Jaret Wright | Jae Weong Seo | Mariano Rivera | 376 | 447 | -71 |
| 2006-07-08 | vs NYA | 88 | L 1-5 | 38-50 | 5 | 34,787 | Scott Kazmir | Chien-Ming Wang | Chien-Ming Wang | Scott Kazmir | | 377 | 452 | -75 |
| 2006-07-09 | vs NYA | 89 | W 6-5 | 39-50 | 5 | 31,583 | Casey Fossum | Kris Wilson | Tim Corcoran | Scott Proctor | Brian Meadows | 383 | 457 | -74 |
| 2006-07-14 | @ ANA | 90 | L 0-4 | 39-51 | 5 | 44,026 | Jae Weong Seo | John Lackey | John Lackey | Jae Weong Seo | | 383 | 461 | -78 |
| 2006-07-15 | @ ANA | 91 | L 2-9 | 39-52 | 5 | 44,125 | James Shields | Ervin Santana | Ervin Santana | James Shields | | 385 | 470 | -85 |
| 2006-07-16 | @ ANA | 92 | L 5-7 | 39-53 | 5 | 41,646 | Casey Fossum | Bartolo Colon | Scot Shields | Chad Harville | Francisco Rodriguez | 390 | 477 | -87 |
| 2006-07-17 | @ MIN | 93 | L 3-6 | 39-54 | 5 | 17,071 | Tim Corcoran | Scott Baker | Scott Baker | Tim Corcoran | Joe Nathan | 393 | 483 | -90 |
| 2006-07-18 | @ MIN | 94 | L 1-8 | 39-55 | 5 | 22,808 | Scott Kazmir | Francisco Liriano | Francisco Liriano | Scott Kazmir | | 394 | 491 | -97 |
| 2006-07-19 | @ MIN | 95 | L 2-7 | 39-56 | 5 | 25,866 | Jae Weong Seo | Brad Radke | Brad Radke | Jae Weong Seo | | 396 | 498 | -102 |
| 2006-07-20 | @ MIN | 96 | L 4-6 | 39-57 | 5 | 25,104 | James Shields | Johan Santana | Johan Santana | James Shields | Joe Nathan | 400 | 504 | -104 |
| 2006-07-21 | vs BAL | 97 | W 14-7 | 40-57 | 5 | 17,759 | Casey Fossum | Russ Ortiz | Casey Fossum | Russ Ortiz | | 414 | 511 | -97 |
| 2006-07-22 | vs BAL | 98 | W 13-12 | 41-57 | 5 | 17,347 | Tim Corcoran | Rodrigo Lopez | Shawn Camp | Rodrigo Lopez | Brian Meadows | 427 | 523 | -96 |
| 2006-07-23 | vs BAL | 99 | L 2-4 | 41-58 | 5 | 23,747 | Scott Kazmir | Erik Bedard | Erik Bedard | Jon Switzer | Chris Ray | 429 | 527 | -98 |
| 2006-07-24 | vs ANA | 100 | L 4-8 | 41-59 | 5 | 11,020 | Jae Weong Seo | John Lackey | John Lackey | Jae Weong Seo | | 433 | 535 | -102 |
| 2006-07-25 | vs ANA | 101 | W 6-3 | 42-59 | 5 | 11,253 | James Shields | Ervin Santana | Jon Switzer | Ervin Santana | | 439 | 538 | -99 |
| 2006-07-26 | vs ANA | 102 | L 6-15 | 42-60 | 5 | 18,525 | Casey Fossum | Bartolo Colon | Kevin Gregg | Casey Fossum | | 445 | 553 | -108 |
| 2006-07-28 | @ NYA | 103 | L 0-6 | 42-61 | 5 | 53,979 | Tim Corcoran | Chien-Ming Wang | Chien-Ming Wang | Tim Corcoran | | 445 | 559 | -114 |
| 2006-07-29 | @ NYA | 104 | W 19-6 | 43-61 | 5 | 54,485 | Jae Weong Seo | Randy Johnson | Jae Weong Seo | Randy Johnson | | 464 | 565 | -101 |
| 2006-07-30 | @ NYA | 105 | L 2-4 | 43-62 | 5 | 54,012 | James Shields | Mike Mussina | Mike Mussina | James Shields | Mariano Rivera | 466 | 569 | -103 |
| 2006-07-31 | vs DET | 106 | W 7-3 | 44-62 | 5 | 15,065 | Casey Fossum | Kenny Rogers | Casey Fossum | Kenny Rogers | | 473 | 572 | -99 |
| 2006-08-01 | vs DET | 107 | L 4-10 | 44-63 | 5 | 13,808 | J.P. Howell | Justin Verlander | Justin Verlander | J.P. Howell | | 477 | 582 | -105 |
| 2006-08-02 | vs DET | 108 | L 3-8 | 44-64 | 5 | 13,126 | Tim Corcoran | Zach Miner | Jason Grilli | Jon Switzer | | 480 | 590 | -110 |
| 2006-08-03 | vs DET | 109 | W 2-1 | 45-64 | 5 | 12,665 | Jae Weong Seo | Nate Robertson | Seth McClung | Nate Robertson | Brian Meadows | 482 | 591 | -109 |
| 2006-08-04 | vs BOS | 110 | L 2-3 | 45-65 | 5 | 27,871 | James Shields | Curt Schilling | Curt Schilling | Seth McClung | Jonathan Papelbon | 484 | 594 | -110 |
| 2006-08-05 | vs BOS | 111 | W 8-5 | 46-65 | 5 | 30,603 | Casey Fossum | David Wells | Casey Fossum | David Wells | Brian Meadows | 492 | 599 | -107 |
| 2006-08-06 | vs BOS | 112 | W 7-6 | 47-65 | 5 | 30,093 | J.P. Howell | Jason Johnson | Shawn Camp | Julian Tavarez | | 499 | 605 | -106 |
| 2006-08-07 | @ SEA | 113 | L 4-5 | 47-66 | 5 | 30,735 | Tim Corcoran | Jamie Moyer | Julio Mateo | Tim Corcoran | J.J. Putz | 503 | 610 | -107 |
| 2006-08-08 | @ SEA | 114 | L 1-5 | 47-67 | 5 | 32,951 | Jae Weong Seo | Felix Hernandez | Julio Mateo | Shawn Camp | | 504 | 615 | -111 |
| 2006-08-09 | @ SEA | 115 | L 0-2 | 47-68 | 5 | 39,856 | James Shields | Jarrod Washburn | Jarrod Washburn | James Shields | J.J. Putz | 504 | 617 | -113 |
| 2006-08-11 | @ OAK | 116 | L 2-5 | 47-69 | 5 | 20,758 | Scott Kazmir | Dan Haren | Dan Haren | Scott Kazmir | Huston Street | 506 | 622 | -116 |
| 2006-08-12 | @ OAK | 117 | L 3-6 | 47-70 | 5 | 26,523 | Casey Fossum | Joe Blanton | Joe Blanton | Casey Fossum | Huston Street | 509 | 628 | -119 |
| 2006-08-13 | @ OAK | 118 | L 1-3 | 47-71 | 5 | 28,692 | Tim Corcoran | Esteban Loaiza | Esteban Loaiza | Tim Corcoran | Huston Street | 510 | 631 | -121 |
| 2006-08-15 | vs TOR | 119 | L 3-4 | 47-72 | 5 | 9,217 | Jae Weong Seo | Roy Halladay | Roy Halladay | Brian Meadows | B.J. Ryan | 513 | 635 | -122 |
| 2006-08-16 | vs TOR | 120 | W 8-3 | 48-72 | 5 | 8,195 | James Shields | Ted Lilly | James Shields | Ted Lilly | | 521 | 638 | -117 |
| 2006-08-17 | vs TOR | 121 | L 2-6 | 48-73 | 5 | 8,697 | Scott Kazmir | A.J. Burnett | A.J. Burnett | Brian Meadows | | 523 | 644 | -121 |
| 2006-08-18 | vs CLE | 122 | W 6-5 | 49-73 | 5 | 15,405 | Casey Fossum | CC Sabathia | Seth McClung | Brian Sikorski | | 529 | 649 | -120 |
| 2006-08-19 | vs CLE | 123 | L 3-5 | 49-74 | 5 | 17,865 | Tim Corcoran | Jeremy Sowers | Jeremy Sowers | Tim Corcoran | Tom Mastny | 532 | 654 | -122 |
| 2006-08-20 | vs CLE | 124 | L 4-9 | 49-75 | 5 | 19,938 | Jae Weong Seo | Jake Westbrook | Jake Westbrook | Chad Orvella | | 536 | 663 | -127 |
| 2006-08-21 | vs TEX | 125 | W 4-3 | 50-75 | 5 | 7,820 | James Shields | Adam Eaton | James Shields | Adam Eaton | Seth McClung | 540 | 666 | -126 |
| 2006-08-22 | vs TEX | 126 | W 5-3 | 51-75 | 5 | 8,028 | Scott Kazmir | Vicente Padilla | Shawn Camp | Vicente Padilla | Seth McClung | 545 | 669 | -124 |
| 2006-08-23 | vs TEX | 127 | W 7-3 | 52-75 | 5 | 9,701 | Casey Fossum | Kevin Millwood | Shawn Camp | Kevin Millwood | | 552 | 672 | -120 |
| 2006-08-24 | vs TEX | 128 | L 3-4 | 52-76 | 5 | 9,454 | Tim Corcoran | Rob Tejeda | Rob Tejeda | Tim Corcoran | Akinori Otsuka | 555 | 676 | -121 |
| 2006-08-25 | @ BAL | 129 | L 0-4 | 52-77 | 5 | 25,510 | Jason Hammel | Daniel Cabrera | Daniel Cabrera | Jason Hammel | Chris Ray | 555 | 680 | -125 |
| 2006-08-26 | @ BAL | 130 | L 2-3 | 52-78 | 5 | 26,379 | James Shields | Erik Bedard | Chris Ray | Shawn Camp | | 557 | 683 | -126 |
| 2006-08-27 | @ BAL | 131 | L 4-5 | 52-79 | 5 | 21,301 | J.P. Howell | Adam Loewen | LaTroy Hawkins | Seth McClung | | 561 | 688 | -127 |
| 2006-08-29 | @ CHA | 132 | L 9-12 | 52-80 | 5 | 35,313 | Casey Fossum | Freddy Garcia | Freddy Garcia | Casey Fossum | Bobby Jenks | 570 | 700 | -130 |
| 2006-08-30 | @ CHA | 133 | L 4-5 | 52-81 | 5 | 35,539 | Tim Corcoran | Jon Garland | Jon Garland | Brian Meadows | Bobby Jenks | 574 | 705 | -131 |
| 2006-08-31 | @ CHA | 134 | W 5-3 | 53-81 | 5 | 33,178 | Jason Hammel | Javier Vazquez | Ruddy Lugo | Brandon McCarthy | Seth McClung | 579 | 708 | -129 |
| 2006-09-01 | vs SEA | 135 | W 2-1 | 54-81 | 5 | 11,196 | James Shields | Gil Meche | Seth McClung | George Sherrill | | 581 | 709 | -128 |
| 2006-09-02 | vs SEA | 136 | L 3-4 | 54-82 | 5 | 14,503 | J.P. Howell | Cha-Seung Baek | Cha-Seung Baek | J.P. Howell | J.J. Putz | 584 | 713 | -129 |
| 2006-09-03 | vs SEA | 137 | W 7-6 | 55-82 | 5 | 14,501 | Brian Stokes | Felix Hernandez | Brian Meadows | Felix Hernandez | Seth McClung | 591 | 719 | -128 |
| 2006-09-04 | vs MIN | 138 | L 1-2 | 55-83 | 5 | 15,910 | Tim Corcoran | Boof Bonser | Boof Bonser | Tim Corcoran | Joe Nathan | 592 | 721 | -129 |
| 2006-09-05 | vs MIN | 139 | L 0-8 | 55-84 | 5 | 8,256 | Jae Weong Seo | Johan Santana | Johan Santana | Jae Weong Seo | | 592 | 729 | -137 |
| 2006-09-06 | vs MIN | 140 | W 4-2 | 56-84 | 5 | 8,942 | Jason Hammel | Carlos Silva | Shawn Camp | Pat Neshek | Seth McClung | 596 | 731 | -135 |
| 2006-09-08 | vs OAK | 141 | L 6-8 | 56-85 | 5 | 12,821 | James Shields | Dan Haren | Dan Haren | James Shields | Huston Street | 602 | 739 | -137 |
| 2006-09-09 | vs OAK | 142 | W 9-6 | 57-85 | 5 | 22,016 | J.P. Howell | Esteban Loaiza | Dan Miceli | Esteban Loaiza | Seth McClung | 611 | 745 | -134 |
| 2006-09-10 | vs OAK | 143 | L 7-9 | 57-86 | 5 | 16,791 | Jae Weong Seo | Barry Zito | Joe Kennedy | Shawn Camp | Huston Street | 618 | 754 | -136 |
| 2006-09-12 | @ NYA | 144 | L 4-12 | 57-87 | 5 | 52,265 | Tim Corcoran | Mike Mussina | Mike Mussina | Tim Corcoran | | 622 | 766 | -144 |
| 2006-09-13 | @ NYA | 145 | L 4-8 | 57-88 | 5 | 52,279 | Jason Hammel | Cory Lidle | Brian Bruney | Jason Hammel | | 626 | 774 | -148 |
| 2006-09-14 | @ NYA | 146 | L 4-7 | 57-89 | 5 | 51,965 | James Shields | Jeff Karstens | Darrell Rasner | Ruddy Lugo | | 630 | 781 | -151 |
| 2006-09-15 | @ TOR | 147 | L 4-5 | 57-90 | 5 | 27,607 | Jae Weong Seo | Roy Halladay | B.J. Ryan | Brian Meadows | | 634 | 786 | -152 |
| 2006-09-16 | @ TOR | 148 | L 1-6 | 57-91 | 5 | 30,698 | J.P. Howell | Ted Lilly | Ted Lilly | J.P. Howell | | 635 | 792 | -157 |
| 2006-09-17 | @ TOR | 149 | L 3-5 | 57-92 | 5 | 32,959 | Brian Stokes | Gustavo Chacin | Justin Speier | Shawn Camp | B.J. Ryan | 638 | 797 | -159 |
| 2006-09-18 | vs BAL | 150 | L 1-4 | 57-93 | 5 | 11,729 | Tim Corcoran | Erik Bedard | Erik Bedard | Tim Corcoran | Chris Ray | 639 | 801 | -162 |
| 2006-09-19 | vs BAL | 151 | L 4-5 | 57-94 | 5 | 9,292 | Jason Hammel | Adam Loewen | Adam Loewen | Jason Hammel | Chris Britton | 643 | 806 | -163 |
| 2006-09-20 | vs BAL | 152 | W 4-2 | 58-94 | 5 | 10,818 | Jae Weong Seo | Hayden Penn | Seth McClung | Rodrigo Lopez | | 647 | 808 | -161 |
| 2006-09-22 | vs NYA | 153 | L 1-4 | 58-95 | 5 | 26,337 | James Shields | Chien-Ming Wang | Chien-Ming Wang | James Shields | Mariano Rivera | 648 | 812 | -164 |
| 2006-09-23 | vs NYA | 154 | W 8-0 | 59-95 | 5 | 33,492 | J.P. Howell | Randy Johnson | J.P. Howell | Randy Johnson | | 656 | 812 | -156 |
| 2006-09-24 | vs NYA | 155 | W 11-4 | 60-95 | 5 | 31,422 | Brian Stokes | Mike Mussina | Brian Stokes | Mike Mussina | | 667 | 816 | -149 |
| 2006-09-25 | vs NYA | 156 | L 1-16 | 60-96 | 5 | 24,053 | Jae Weong Seo | Jaret Wright | Jaret Wright | Jae Weong Seo | | 668 | 832 | -164 |
| 2006-09-26 | @ BOS | 157 | L 1-5 | 60-97 | 5 | 36,134 | Jason Hammel | Curt Schilling | Curt Schilling | Jason Hammel | | 669 | 837 | -168 |
| 2006-09-27 | @ BOS | 158 | W 11-0 | 61-97 | 5 | 36,028 | Tim Corcoran | Josh Beckett | Tim Corcoran | Josh Beckett | | 680 | 837 | -157 |
| 2006-09-28 | @ CLE | 159 | L 4-5 | 61-98 | 5 | 14,503 | J.P. Howell | Paul Byrd | Paul Byrd | Ruddy Lugo | Rafael Betancourt | 684 | 842 | -158 |
| 2006-09-29 | @ CLE | 160 | L 1-2 | 61-99 | 5 | 19,983 | Brian Stokes | Brian Slocum | Brian Sikorski | Dan Miceli | | 685 | 844 | -159 |
| 2006-09-30 | @ CLE | 161 | L 1-6 | 61-100 | 5 | 17,562 | Jae Weong Seo | Jake Westbrook | Jake Westbrook | Jae Weong Seo | | 686 | 850 | -164 |
| 2006-10-01 | @ CLE | 162 | L 3-6 | 61-101 | 5 | 22,079 | Jason Hammel | Cliff Lee | Cliff Lee | Jason Hammel | | 689 | 856 | -167 |