| 2006-04-03 | vs NYA | 1 | L 2-15 | 0-1 | 2 | 35,077 | Barry Zito | Randy Johnson | Randy Johnson | Barry Zito | | 2 | 15 | -13 |
| 2006-04-04 | vs NYA | 2 | W 4-3 | 1-1 | 1 | 31,284 | Rich Harden | Mike Mussina | Huston Street | Scott Proctor | | 6 | 18 | -12 |
| 2006-04-05 | vs NYA | 3 | W 9-4 | 2-1 | 1 | 30,165 | Dan Haren | Chien-Ming Wang | Joe Kennedy | Jaret Wright | | 15 | 22 | -7 |
| 2006-04-06 | @ SEA | 4 | L 2-6 | 2-2 | 2 | 22,701 | Esteban Loaiza | Gil Meche | Gil Meche | Esteban Loaiza | J.J. Putz | 17 | 28 | -11 |
| 2006-04-07 | @ SEA | 5 | W 5-0 | 3-2 | 1 | 30,612 | Joe Blanton | Felix Hernandez | Joe Blanton | Felix Hernandez | | 22 | 28 | -6 |
| 2006-04-08 | @ SEA | 6 | W 3-0 | 4-2 | 1 | 37,904 | Barry Zito | Jamie Moyer | Barry Zito | Jamie Moyer | Huston Street | 25 | 28 | -3 |
| 2006-04-09 | @ SEA | 7 | W 6-4 | 5-2 | 1 | 27,139 | Rich Harden | Joel Pineiro | Rich Harden | Joel Pineiro | Huston Street | 31 | 32 | -1 |
| 2006-04-11 | @ MIN | 8 | L 6-7 | 5-3 | 1 | 48,911 | Dan Haren | Brad Radke | Brad Radke | Dan Haren | Joe Nathan | 37 | 39 | -2 |
| 2006-04-12 | @ MIN | 9 | L 5-6 | 5-4 | 1 | 22,603 | Esteban Loaiza | Carlos Silva | Carlos Silva | Esteban Loaiza | Joe Nathan | 42 | 45 | -3 |
| 2006-04-13 | @ MIN | 10 | L 2-8 | 5-5 | 2 | 13,520 | Joe Blanton | Kyle Lohse | Kyle Lohse | Joe Blanton | | 44 | 53 | -9 |
| 2006-04-14 | vs TEX | 11 | L 3-6 | 5-6 | 2 | 14,049 | Barry Zito | Kevin Millwood | Kevin Millwood | Barry Zito | | 47 | 59 | -12 |
| 2006-04-15 | vs TEX | 12 | W 5-4 | 6-6 | 1 | 16,186 | Rich Harden | Vicente Padilla | Rich Harden | Vicente Padilla | Huston Street | 52 | 63 | -11 |
| 2006-04-16 | vs TEX | 13 | L 3-5 | 6-7 | 2 | 21,256 | Dan Haren | Kameron Loe | Francisco Cordero | Huston Street | | 55 | 68 | -13 |
| 2006-04-18 | vs DET | 14 | W 4-3 | 7-7 | 1 | 16,857 | Esteban Loaiza | Justin Verlander | Justin Duchscherer | Justin Verlander | Huston Street | 59 | 71 | -12 |
| 2006-04-19 | vs DET | 15 | L 4-11 | 7-8 | 1 | 18,309 | Joe Blanton | Kenny Rogers | Kenny Rogers | Joe Blanton | | 63 | 82 | -19 |
| 2006-04-20 | vs DET | 16 | L 3-4 | 7-9 | 2 | 15,489 | Barry Zito | Jeremy Bonderman | Fernando Rodney | Justin Duchscherer | | 66 | 86 | -20 |
| 2006-04-21 | vs ANA | 17 | W 5-3 | 8-9 | 1 | 19,874 | Rich Harden | John Lackey | Rich Harden | J.C. Romero | Kiko Calero | 71 | 89 | -18 |
| 2006-04-22 | vs ANA | 18 | L 4-5 | 8-10 | 3 | 22,670 | Dan Haren | Jeff Weaver | Jeff Weaver | Dan Haren | Francisco Rodriguez | 75 | 94 | -19 |
| 2006-04-23 | vs ANA | 19 | L 3-4 | 8-11 | 3 | 27,104 | Esteban Loaiza | Kelvim Escobar | Kelvim Escobar | Esteban Loaiza | Francisco Rodriguez | 78 | 98 | -20 |
| 2006-04-24 | @ TEX | 20 | W 3-2 | 9-11 | 3 | 23,802 | Joe Blanton | Kevin Millwood | Joe Blanton | C.J. Wilson | Justin Duchscherer | 81 | 100 | -19 |
| 2006-04-25 | @ TEX | 21 | L 5-6 | 9-12 | 3 | 25,492 | Barry Zito | Vicente Padilla | Francisco Cordero | Chad Gaudin | | 86 | 106 | -20 |
| 2006-04-26 | @ TEX | 22 | W 6-4 | 10-12 | 3 | 23,756 | Rich Harden | Kameron Loe | Justin Duchscherer | C.J. Wilson | Joe Kennedy | 92 | 110 | -18 |
| 2006-04-28 | @ KCA | 23 | W 5-3 | 11-12 | 2 | 12,203 | Dan Haren | Joe Mays | Dan Haren | Joe Mays | Kirk Saarloos | 97 | 113 | -16 |
| 2006-04-30 | @ KCA | 24 | W 13-6 | 12-12 | 2 | 15,224 | Joe Blanton | Scott Elarton | Joe Blanton | Luke Hudson | | 110 | 119 | -9 |
| 2006-05-01 | @ ANA | 25 | W 1-0 | 13-12 | 2 | 41,721 | Barry Zito | Hector Carrasco | Barry Zito | Hector Carrasco | Justin Duchscherer | 111 | 119 | -8 |
| 2006-05-02 | @ ANA | 26 | W 10-3 | 14-12 | 2 | 35,943 | Brad Halsey | John Lackey | Brad Halsey | John Lackey | | 121 | 122 | -1 |
| 2006-05-03 | vs CLE | 27 | L 3-14 | 14-13 | 2 | 18,248 | Dan Haren | Paul Byrd | Paul Byrd | Dan Haren | | 124 | 136 | -12 |
| 2006-05-04 | vs CLE | 28 | W 12-4 | 15-13 | 2 | 14,695 | Kirk Saarloos | Jason Johnson | Kirk Saarloos | Jason Johnson | Chad Gaudin | 136 | 140 | -4 |
| 2006-05-05 | vs TBA | 29 | L 1-3 | 15-14 | 2 | 12,552 | Joe Blanton | Scott Kazmir | Scott Kazmir | Joe Blanton | Tyler Walker | 137 | 143 | -6 |
| 2006-05-06 | vs TBA | 30 | W 3-2 | 16-14 | 2 | 25,080 | Barry Zito | Seth McClung | Joe Kennedy | Chad Orvella | | 140 | 145 | -5 |
| 2006-05-07 | vs TBA | 31 | L 2-3 | 16-15 | 2 | 22,837 | Brad Halsey | Mark Hendrickson | Mark Hendrickson | Brad Halsey | Tyler Walker | 142 | 148 | -6 |
| 2006-05-09 | @ TOR | 32 | W 6-5 | 17-15 | 1 | 36,269 | Dan Haren | Josh Towers | Dan Haren | Josh Towers | Huston Street | 148 | 153 | -5 |
| 2006-05-10 | @ TOR | 33 | L 7-9 | 17-16 | 1 | 19,269 | Joe Blanton | Gustavo Chacin | Francisco Rosario | Joe Blanton | B.J. Ryan | 155 | 162 | -7 |
| 2006-05-11 | @ TOR | 34 | L 3-8 | 17-17 | 2 | 23,974 | Kirk Saarloos | Ted Lilly | Ted Lilly | Kirk Saarloos | | 158 | 170 | -12 |
| 2006-05-12 | @ NYA | 35 | L 0-2 | 17-18 | 2 | 47,497 | Barry Zito | Chien-Ming Wang | Chien-Ming Wang | Barry Zito | Mariano Rivera | 158 | 172 | -14 |
| 2006-05-13 | @ NYA | 36 | L 3-4 | 17-19 | 2 | 53,907 | Brad Halsey | Jaret Wright | Jaret Wright | Brad Halsey | Kyle Farnsworth | 161 | 176 | -15 |
| 2006-05-14 | @ NYA | 37 | W 6-1 | 18-19 | 2 | 52,587 | Dan Haren | Randy Johnson | Dan Haren | Randy Johnson | | 167 | 177 | -10 |
| 2006-05-16 | vs SEA | 38 | W 12-6 | 19-19 | 2 | 16,397 | Joe Blanton | Felix Hernandez | Joe Blanton | Felix Hernandez | | 179 | 183 | -4 |
| 2006-05-17 | vs SEA | 39 | W 7-2 | 20-19 | 1 | 19,208 | Barry Zito | Jamie Moyer | Barry Zito | Jamie Moyer | | 186 | 185 | 1 |
| 2006-05-18 | vs SEA | 40 | W 6-3 | 21-19 | 1 | 18,136 | Kirk Saarloos | Joel Pineiro | Kirk Saarloos | Joel Pineiro | Huston Street | 192 | 188 | 4 |
| 2006-05-19 | vs SFN | 41 | W 1-0 | 22-19 | 1 | 35,077 | Dan Haren | Noah Lowry | Dan Haren | Noah Lowry | Huston Street | 193 | 188 | 5 |
| 2006-05-20 | vs SFN | 42 | L 2-4 | 22-20 | 1 | 35,077 | Brad Halsey | Jason Schmidt | Armando Benitez | Kiko Calero | | 195 | 192 | 3 |
| 2006-05-21 | vs SFN | 43 | L 0-6 | 22-21 | 1 | 35,077 | Joe Blanton | Matt Cain | Matt Cain | Joe Blanton | | 195 | 198 | -3 |
| 2006-05-22 | @ CHA | 44 | L 4-5 | 22-22 | 2 | 39,354 | Barry Zito | Jon Garland | Bobby Jenks | Ron Flores | | 199 | 203 | -4 |
| 2006-05-23 | @ CHA | 45 | L 3-9 | 22-23 | 2 | 38,860 | Kirk Saarloos | Javier Vazquez | Javier Vazquez | Kirk Saarloos | | 202 | 212 | -10 |
| 2006-05-24 | @ CHA | 46 | L 2-3 | 22-24 | 2 | 38,434 | Dan Haren | Mark Buehrle | Mark Buehrle | Dan Haren | Bobby Jenks | 204 | 215 | -11 |
| 2006-05-25 | @ TEX | 47 | L 7-8 | 22-25 | 2 | 22,006 | Brad Halsey | Kevin Millwood | Akinori Otsuka | Huston Street | | 211 | 223 | -12 |
| 2006-05-26 | @ TEX | 48 | L 3-5 | 22-26 | 2 | 27,791 | Joe Blanton | John Koronka | Francisco Cordero | Chad Gaudin | Akinori Otsuka | 214 | 228 | -14 |
| 2006-05-27 | @ TEX | 49 | W 6-3 | 23-26 | 2 | 41,226 | Barry Zito | Kameron Loe | Barry Zito | Kameron Loe | Huston Street | 220 | 231 | -11 |
| 2006-05-28 | @ TEX | 50 | L 3-4 | 23-27 | 2 | 38,905 | Kirk Saarloos | Vicente Padilla | Vicente Padilla | Kirk Saarloos | Akinori Otsuka | 223 | 235 | -12 |
| 2006-05-29 | vs KCA | 51 | L 4-6 | 23-28 | 2 | 28,040 | Dan Haren | Seth Etherton | Seth Etherton | Dan Haren | Ambiorix Burgos | 227 | 241 | -14 |
| 2006-05-30 | vs KCA | 52 | L 7-8 | 23-29 | 2 | 12,516 | Brad Halsey | Denny Bautista | Elmer Dessens | Matt Roney | Ambiorix Burgos | 234 | 249 | -15 |
| 2006-05-31 | vs KCA | 53 | W 7-0 | 24-29 | 2 | 25,181 | Joe Blanton | Scott Elarton | Joe Blanton | Scott Elarton | | 241 | 249 | -8 |
| 2006-06-01 | vs MIN | 54 | W 4-0 | 25-29 | 2 | 12,025 | Barry Zito | Boof Bonser | Barry Zito | Boof Bonser | | 245 | 249 | -4 |
| 2006-06-02 | vs MIN | 55 | L 1-2 | 25-30 | 2 | 16,138 | Kirk Saarloos | Johan Santana | Johan Santana | Kirk Saarloos | Joe Nathan | 246 | 251 | -5 |
| 2006-06-03 | vs MIN | 56 | W 2-1 | 26-30 | 2 | 23,194 | Dan Haren | Brad Radke | Brad Halsey | Brad Radke | Huston Street | 248 | 252 | -4 |
| 2006-06-04 | vs MIN | 57 | W 5-1 | 27-30 | 2 | 25,247 | Rich Harden | Carlos Silva | Brad Halsey | Carlos Silva | | 253 | 253 | 0 |
| 2006-06-06 | @ CLE | 58 | W 7-6 | 28-30 | 2 | 17,340 | Barry Zito | Jake Westbrook | Barry Zito | Rafael Betancourt | Huston Street | 260 | 259 | 1 |
| 2006-06-07 | @ CLE | 59 | L 2-11 | 28-31 | 2 | 20,311 | Joe Blanton | Paul Byrd | Paul Byrd | Joe Blanton | | 262 | 270 | -8 |
| 2006-06-08 | @ CLE | 60 | W 4-1 | 29-31 | 2 | 21,099 | Esteban Loaiza | Jason Johnson | Esteban Loaiza | Jason Johnson | Huston Street | 266 | 271 | -5 |
| 2006-06-09 | @ NYA | 61 | W 6-5 | 30-31 | 2 | 53,837 | Dan Haren | Randy Johnson | Dan Haren | Randy Johnson | Huston Street | 272 | 276 | -4 |
| 2006-06-10 | @ NYA | 62 | W 5-2 | 31-31 | 2 | 53,779 | Kirk Saarloos | Mike Mussina | Kirk Saarloos | Mike Mussina | Huston Street | 277 | 278 | -1 |
| 2006-06-11 | @ NYA | 63 | W 6-5 | 32-31 | 2 | 54,570 | Barry Zito | Shawn Chacon | Barry Zito | Kyle Farnsworth | Huston Street | 283 | 283 | 0 |
| 2006-06-13 | vs SEA | 64 | W 2-0 | 33-31 | 2 | 15,216 | Joe Blanton | Jamie Moyer | Joe Blanton | Jamie Moyer | Huston Street | 285 | 283 | 2 |
| 2006-06-14 | vs SEA | 65 | W 7-2 | 34-31 | 2 | 20,550 | Dan Haren | Joel Pineiro | Dan Haren | Joel Pineiro | | 292 | 285 | 7 |
| 2006-06-15 | vs SEA | 66 | W 9-6 | 35-31 | 1 | 16,563 | Esteban Loaiza | Jarrod Washburn | Esteban Loaiza | Jarrod Washburn | Huston Street | 301 | 291 | 10 |
| 2006-06-16 | vs LAN | 67 | W 7-3 | 36-31 | 1 | 30,161 | Barry Zito | Brett Tomko | Barry Zito | Brett Tomko | | 308 | 294 | 14 |
| 2006-06-17 | vs LAN | 68 | W 5-4 | 37-31 | 1 | 35,077 | Kirk Saarloos | Derek Lowe | Steve Karsay | Jae Weong Seo | | 313 | 298 | 15 |
| 2006-06-18 | vs LAN | 69 | W 5-2 | 38-31 | 1 | 35,077 | Joe Blanton | Aaron Sele | Joe Blanton | Aaron Sele | Huston Street | 318 | 300 | 18 |
| 2006-06-19 | @ COL | 70 | L 0-7 | 38-32 | 1 | 21,964 | Dan Haren | Byung-Hyun Kim | Byung-Hyun Kim | Dan Haren | | 318 | 307 | 11 |
| 2006-06-20 | @ COL | 71 | L 0-6 | 38-33 | 1 | 21,753 | Esteban Loaiza | Jason Jennings | Jason Jennings | Esteban Loaiza | | 318 | 313 | 5 |
| 2006-06-21 | @ COL | 72 | W 3-2 | 39-33 | 1 | 26,489 | Barry Zito | Aaron Cook | Kiko Calero | Ray King | | 321 | 315 | 6 |
| 2006-06-23 | @ SFN | 73 | W 4-3 | 40-33 | 1 | 42,948 | Joe Blanton | Jason Schmidt | Kiko Calero | Armando Benitez | Huston Street | 325 | 318 | 7 |
| 2006-06-24 | @ SFN | 74 | L 7-8 | 40-34 | 1 | 42,866 | Dan Haren | Jamey Wright | Tim Worrell | Huston Street | | 332 | 326 | 6 |
| 2006-06-25 | @ SFN | 75 | W 10-4 | 41-34 | 1 | 42,414 | Esteban Loaiza | Matt Cain | Esteban Loaiza | Matt Cain | | 342 | 330 | 12 |
| 2006-06-27 | @ SDN | 76 | L 0-3 | 41-35 | 1 | 34,102 | Barry Zito | Chris Young | Chris Young | Barry Zito | Trevor Hoffman | 342 | 333 | 9 |
| 2006-06-28 | @ SDN | 77 | L 1-8 | 41-36 | 1 | 39,874 | Joe Blanton | Clay Hensley | Clay Hensley | Joe Blanton | | 343 | 341 | 2 |
| 2006-06-29 | @ SDN | 78 | W 6-5 | 42-36 | 1 | 30,301 | Dan Haren | Jake Peavy | Ron Flores | Scott Cassidy | Chad Gaudin | 349 | 346 | 3 |
| 2006-06-30 | vs ARI | 79 | L 4-6 | 42-37 | 1 | 16,756 | Kirk Saarloos | Claudio Vargas | Claudio Vargas | Brad Halsey | Jorge Julio | 353 | 352 | 1 |
| 2006-07-01 | vs ARI | 80 | L 2-7 | 42-38 | 1 | 19,024 | Esteban Loaiza | Miguel Batista | Miguel Batista | Esteban Loaiza | | 355 | 359 | -4 |
| 2006-07-02 | vs ARI | 81 | L 1-3 | 42-39 | 1 | 19,130 | Barry Zito | Brandon Webb | Brandon Webb | Barry Zito | | 356 | 362 | -6 |
| 2006-07-03 | vs DET | 82 | W 5-3 | 43-39 | 1 | 35,077 | Joe Blanton | Nate Robertson | Joe Blanton | Nate Robertson | Huston Street | 361 | 365 | -4 |
| 2006-07-04 | vs DET | 83 | W 2-1 | 44-39 | 1 | 21,096 | Dan Haren | Justin Verlander | Chad Gaudin | Fernando Rodney | | 363 | 366 | -3 |
| 2006-07-05 | vs DET | 84 | L 4-10 | 44-40 | 1 | 22,210 | Kirk Saarloos | Kenny Rogers | Kenny Rogers | Kirk Saarloos | Roman Colon | 367 | 376 | -9 |
| 2006-07-06 | vs ANA | 85 | W 7-5 | 45-40 | 1 | 14,673 | Esteban Loaiza | Kelvim Escobar | Huston Street | Scot Shields | | 374 | 381 | -7 |
| 2006-07-07 | vs ANA | 86 | L 0-3 | 45-41 | 1 | 20,711 | Barry Zito | John Lackey | John Lackey | Barry Zito | | 374 | 384 | -10 |
| 2006-07-08 | vs ANA | 87 | L 4-6 | 45-42 | 1 | 25,289 | Joe Blanton | Jered Weaver | Jered Weaver | Joe Blanton | Francisco Rodriguez | 378 | 390 | -12 |
| 2006-07-09 | vs ANA | 88 | L 2-4 | 45-43 | 1 | 26,603 | Dan Haren | Ervin Santana | Ervin Santana | Dan Haren | Francisco Rodriguez | 380 | 394 | -14 |
| 2006-07-13 | @ BOS | 89 | W 5-4 | 46-43 | 1 | 36,141 | Esteban Loaiza | Jon Lester | Huston Street | Julian Tavarez | Kirk Saarloos | 385 | 398 | -13 |
| 2006-07-14 | @ BOS | 90 | W 15-3 | 47-43 | 1 | 36,319 | Barry Zito | Josh Beckett | Barry Zito | Josh Beckett | | 400 | 401 | -1 |
| 2006-07-15 | @ BOS | 91 | L 0-7 | 47-44 | 1 | 36,232 | Dan Haren | Curt Schilling | Curt Schilling | Dan Haren | | 400 | 408 | -8 |
| 2006-07-16 | @ BOS | 92 | W 8-1 | 48-44 | 1 | 35,643 | Joe Blanton | Kyle Snyder | Joe Blanton | Kyle Snyder | | 408 | 409 | -1 |
| 2006-07-17 | @ BAL | 93 | L 3-5 | 48-45 | 1 | 19,652 | Jason Windsor | Adam Loewen | Kurt Birkins | Kirk Saarloos | Chris Ray | 411 | 414 | -3 |
| 2006-07-18 | @ BAL | 94 | W 5-4 | 49-45 | 1 | 20,827 | Esteban Loaiza | Russ Ortiz | Esteban Loaiza | Eddy Rodriguez | Huston Street | 416 | 418 | -2 |
| 2006-07-19 | @ BAL | 95 | W 5-1 | 50-45 | 1 | 29,407 | Barry Zito | Kris Benson | Barry Zito | Kris Benson | | 421 | 419 | 2 |
| 2006-07-21 | @ DET | 96 | L 4-7 | 50-46 | 1 | 40,687 | Dan Haren | Justin Verlander | Justin Verlander | Dan Haren | | 425 | 426 | -1 |
| 2006-07-22 | @ DET | 97 | W 9-5 | 51-46 | 1 | 38,923 | Joe Blanton | Zach Miner | Joe Blanton | Wil Ledezma | | 434 | 431 | 3 |
| 2006-07-23 | @ DET | 98 | L 4-8 | 51-47 | 1 | 40,355 | Esteban Loaiza | Nate Robertson | Nate Robertson | Esteban Loaiza | | 438 | 439 | -1 |
| 2006-07-24 | vs BOS | 99 | L 3-7 | 51-48 | 1 | 33,370 | Barry Zito | Josh Beckett | Josh Beckett | Barry Zito | | 441 | 446 | -5 |
| 2006-07-25 | vs BOS | 100 | L 5-13 | 51-49 | 1 | 34,077 | Jason Windsor | Curt Schilling | Curt Schilling | Jason Windsor | | 446 | 459 | -13 |
| 2006-07-26 | vs BOS | 101 | W 5-1 | 52-49 | 1 | 35,077 | Dan Haren | Kyle Snyder | Dan Haren | Kyle Snyder | | 451 | 460 | -9 |
| 2006-07-27 | vs TOR | 102 | W 5-2 | 53-49 | 1 | 19,251 | Joe Blanton | Ted Lilly | Joe Blanton | Ted Lilly | Huston Street | 456 | 462 | -6 |
| 2006-07-28 | vs TOR | 103 | L 3-4 | 53-50 | 2 | 22,217 | Esteban Loaiza | Shaun Marcum | Scott Downs | Esteban Loaiza | B.J. Ryan | 459 | 466 | -7 |
| 2006-07-29 | vs TOR | 104 | W 7-4 | 54-50 | 1 | 25,627 | Barry Zito | Dustin McGowan | Barry Zito | Dustin McGowan | Huston Street | 466 | 470 | -4 |
| 2006-07-30 | vs TOR | 105 | W 6-5 | 55-50 | 1 | 29,709 | Shane Komine | Roy Halladay | Huston Street | B.J. Ryan | | 472 | 475 | -3 |
| 2006-07-31 | @ ANA | 106 | W 3-1 | 56-50 | 1 | 43,558 | Dan Haren | Ervin Santana | Dan Haren | Ervin Santana | | 475 | 476 | -1 |
| 2006-08-01 | @ ANA | 107 | L 2-3 | 56-51 | 1 | 44,111 | Joe Blanton | Joe Saunders | Joe Saunders | Joe Blanton | Francisco Rodriguez | 477 | 479 | -2 |
| 2006-08-02 | @ ANA | 108 | W 3-2 | 57-51 | 1 | 44,149 | Esteban Loaiza | Kelvim Escobar | Kiko Calero | Scot Shields | Huston Street | 480 | 481 | -1 |
| 2006-08-04 | @ SEA | 109 | W 5-2 | 58-51 | 1 | 44,277 | Barry Zito | Jarrod Washburn | Barry Zito | Jarrod Washburn | | 485 | 483 | 2 |
| 2006-08-05 | @ SEA | 110 | W 5-2 | 59-51 | 1 | 40,115 | Dan Haren | Joel Pineiro | Dan Haren | Joel Pineiro | Huston Street | 490 | 485 | 5 |
| 2006-08-06 | @ SEA | 111 | W 7-6 | 60-51 | 1 | 37,437 | Joe Blanton | Gil Meche | Joe Blanton | Gil Meche | Huston Street | 497 | 491 | 6 |
| 2006-08-07 | vs TEX | 112 | W 7-4 | 61-51 | 1 | 21,208 | Esteban Loaiza | Edinson Volquez | Esteban Loaiza | Edinson Volquez | Kiko Calero | 504 | 495 | 9 |
| 2006-08-08 | vs TEX | 113 | W 7-6 | 62-51 | 1 | 21,650 | Shane Komine | Kevin Millwood | Kirk Saarloos | Kevin Millwood | Huston Street | 511 | 501 | 10 |
| 2006-08-09 | vs TEX | 114 | L 0-14 | 62-52 | 1 | 30,127 | Barry Zito | Vicente Padilla | Vicente Padilla | Barry Zito | | 511 | 515 | -4 |
| 2006-08-11 | vs TBA | 115 | W 5-2 | 63-52 | 1 | 20,758 | Dan Haren | Scott Kazmir | Dan Haren | Scott Kazmir | Huston Street | 516 | 517 | -1 |
| 2006-08-12 | vs TBA | 116 | W 6-3 | 64-52 | 1 | 26,523 | Joe Blanton | Casey Fossum | Joe Blanton | Casey Fossum | Huston Street | 522 | 520 | 2 |
| 2006-08-13 | vs TBA | 117 | W 3-1 | 65-52 | 1 | 28,692 | Esteban Loaiza | Tim Corcoran | Esteban Loaiza | Tim Corcoran | Huston Street | 525 | 521 | 4 |
| 2006-08-14 | vs SEA | 118 | W 5-4 | 66-52 | 1 | 21,859 | Barry Zito | Jarrod Washburn | Joe Kennedy | Rafael Soriano | Justin Duchscherer | 530 | 525 | 5 |
| 2006-08-15 | vs SEA | 119 | W 11-2 | 67-52 | 1 | 23,726 | Kirk Saarloos | Joel Pineiro | Kirk Saarloos | Joel Pineiro | | 541 | 527 | 14 |
| 2006-08-16 | vs SEA | 120 | W 4-0 | 68-52 | 1 | 34,077 | Dan Haren | Gil Meche | Dan Haren | Gil Meche | | 545 | 527 | 18 |
| 2006-08-18 | @ KCA | 121 | L 1-7 | 68-54 | 1 | 0 | Joe Blanton | Luke Hudson | Luke Hudson | Joe Blanton | | 546 | 534 | 12 |
| 2006-08-18 | @ KCA | 122 | L 3-5 | 68-54 | 1 | 23,952 | Esteban Loaiza | Jorge de la Rosa | Ambiorix Burgos | Huston Street | Joe Nelson | 549 | 539 | 10 |
| 2006-08-19 | @ KCA | 123 | W 7-2 | 69-54 | 1 | 30,810 | Barry Zito | Mark Redman | Barry Zito | Mark Redman | | 556 | 541 | 15 |
| 2006-08-20 | @ KCA | 124 | W 6-4 | 70-54 | 1 | 16,592 | Kirk Saarloos | Runelvys Hernandez | Kirk Saarloos | Runelvys Hernandez | | 562 | 545 | 17 |
| 2006-08-21 | @ TOR | 125 | W 12-10 | 71-54 | 1 | 28,280 | Dan Haren | Ted Lilly | Dan Haren | Brandon League | Justin Duchscherer | 574 | 555 | 19 |
| 2006-08-22 | @ TOR | 126 | L 3-4 | 71-55 | 1 | 30,071 | Brad Halsey | A.J. Burnett | A.J. Burnett | Brad Halsey | B.J. Ryan | 577 | 559 | 18 |
| 2006-08-23 | @ TOR | 127 | W 6-0 | 72-55 | 1 | 32,516 | Esteban Loaiza | Gustavo Chacin | Esteban Loaiza | Gustavo Chacin | | 583 | 559 | 24 |
| 2006-08-25 | @ TEX | 128 | W 9-3 | 73-55 | 1 | 31,178 | Barry Zito | Edinson Volquez | Barry Zito | Edinson Volquez | | 592 | 562 | 30 |
| 2006-08-26 | @ TEX | 129 | W 5-3 | 74-55 | 1 | 37,752 | Joe Blanton | Adam Eaton | Joe Blanton | Adam Eaton | Justin Duchscherer | 597 | 565 | 32 |
| 2006-08-27 | @ TEX | 130 | L 0-3 | 74-56 | 1 | 25,708 | Dan Haren | Vicente Padilla | Vicente Padilla | Dan Haren | Akinori Otsuka | 597 | 568 | 29 |
| 2006-08-28 | vs BOS | 131 | W 9-0 | 75-56 | 1 | 30,159 | Esteban Loaiza | Kason Gabbard | Esteban Loaiza | Kason Gabbard | | 606 | 568 | 38 |
| 2006-08-29 | vs BOS | 132 | W 2-1 | 76-56 | 1 | 30,517 | Kirk Saarloos | Josh Beckett | Kirk Saarloos | Josh Beckett | Justin Duchscherer | 608 | 569 | 39 |
| 2006-08-30 | vs BOS | 133 | W 7-2 | 77-56 | 1 | 31,073 | Barry Zito | Curt Schilling | Barry Zito | Curt Schilling | | 615 | 571 | 44 |
| 2006-09-01 | vs BAL | 134 | W 5-4 | 78-56 | 1 | 31,179 | Joe Blanton | Erik Bedard | Brad Halsey | Todd Williams | Justin Duchscherer | 620 | 575 | 45 |
| 2006-09-02 | vs BAL | 135 | L 5-6 | 78-57 | 1 | 24,383 | Dan Haren | Adam Loewen | Adam Loewen | Dan Haren | Chris Ray | 625 | 581 | 44 |
| 2006-09-03 | vs BAL | 136 | W 10-1 | 79-57 | 1 | 26,280 | Esteban Loaiza | Hayden Penn | Esteban Loaiza | Hayden Penn | | 635 | 582 | 53 |
| 2006-09-04 | vs TEX | 137 | L 1-8 | 79-58 | 1 | 23,949 | Barry Zito | Rob Tejeda | Rob Tejeda | Barry Zito | | 636 | 590 | 46 |
| 2006-09-05 | vs TEX | 138 | L 4-5 | 79-59 | 1 | 27,225 | Kirk Saarloos | Adam Eaton | Adam Eaton | Kirk Saarloos | Akinori Otsuka | 640 | 595 | 45 |
| 2006-09-06 | vs TEX | 139 | W 9-6 | 80-59 | 1 | 17,838 | Joe Blanton | Vicente Padilla | Joe Blanton | Josh Rupe | Justin Duchscherer | 649 | 601 | 48 |
| 2006-09-08 | @ TBA | 140 | W 8-6 | 81-59 | 1 | 12,821 | Dan Haren | James Shields | Dan Haren | James Shields | Huston Street | 657 | 607 | 50 |
| 2006-09-09 | @ TBA | 141 | L 6-9 | 81-60 | 1 | 22,016 | Esteban Loaiza | J.P. Howell | Dan Miceli | Esteban Loaiza | Seth McClung | 663 | 616 | 47 |
| 2006-09-10 | @ TBA | 142 | W 9-7 | 82-60 | 1 | 16,791 | Barry Zito | Jae Weong Seo | Joe Kennedy | Shawn Camp | Huston Street | 672 | 623 | 49 |
| 2006-09-11 | @ MIN | 143 | L 4-9 | 82-61 | 1 | 15,728 | Joe Blanton | Carlos Silva | Carlos Silva | Joe Blanton | Joe Nathan | 676 | 632 | 44 |
| 2006-09-12 | @ MIN | 144 | L 5-7 | 82-62 | 1 | 20,991 | Kirk Saarloos | Matt Guerrier | Dennys Reyes | Joe Kennedy | Joe Nathan | 681 | 639 | 42 |
| 2006-09-13 | @ MIN | 145 | W 1-0 | 83-62 | 1 | 18,902 | Dan Haren | Francisco Liriano | Dan Haren | Matt Garza | Huston Street | 682 | 639 | 43 |
| 2006-09-15 | vs CHA | 146 | W 4-2 | 84-62 | 1 | 26,809 | Esteban Loaiza | Jon Garland | Esteban Loaiza | Jon Garland | Huston Street | 686 | 641 | 45 |
| 2006-09-16 | vs CHA | 147 | W 7-4 | 85-62 | 1 | 32,169 | Barry Zito | Javier Vazquez | Barry Zito | Matt Thornton | Huston Street | 693 | 645 | 48 |
| 2006-09-17 | vs CHA | 148 | W 5-4 | 86-62 | 1 | 28,806 | Joe Blanton | Jose Contreras | Joe Blanton | Jose Contreras | Justin Duchscherer | 698 | 649 | 49 |
| 2006-09-18 | vs CLE | 149 | L 2-7 | 86-63 | 1 | 17,352 | Dan Haren | Jake Westbrook | Jake Westbrook | Dan Haren | | 700 | 656 | 44 |
| 2006-09-19 | vs CLE | 150 | W 7-3 | 87-63 | 1 | 15,866 | Kirk Saarloos | Cliff Lee | Chad Gaudin | Cliff Lee | | 707 | 659 | 48 |
| 2006-09-20 | vs CLE | 151 | W 4-3 | 88-63 | 1 | 25,131 | Esteban Loaiza | Fausto Carmona | Esteban Loaiza | Fernando Cabrera | Huston Street | 711 | 662 | 49 |
| 2006-09-21 | vs CLE | 152 | W 7-4 | 89-63 | 1 | 20,452 | Rich Harden | CC Sabathia | Chad Gaudin | CC Sabathia | Huston Street | 718 | 666 | 52 |
| 2006-09-22 | vs ANA | 153 | W 5-4 | 90-63 | 1 | 35,077 | Barry Zito | Jered Weaver | Brad Halsey | Francisco Rodriguez | | 723 | 670 | 53 |
| 2006-09-23 | vs ANA | 154 | L 2-6 | 90-64 | 1 | 34,077 | Joe Blanton | John Lackey | John Lackey | Joe Blanton | | 725 | 676 | 49 |
| 2006-09-24 | vs ANA | 155 | L 1-7 | 90-65 | 1 | 34,077 | Dan Haren | Ervin Santana | Ervin Santana | Dan Haren | | 726 | 683 | 43 |
| 2006-09-25 | @ SEA | 156 | L 9-10 | 90-66 | 1 | 20,982 | Esteban Loaiza | Cesar Jimenez | J.J. Putz | Kiko Calero | | 735 | 693 | 42 |
| 2006-09-26 | @ SEA | 157 | W 12-3 | 91-66 | 1 | 19,604 | Rich Harden | Jake Woods | Rich Harden | Jake Woods | | 747 | 696 | 51 |
| 2006-09-27 | @ SEA | 158 | W 7-6 | 92-66 | 1 | 23,421 | Jason Windsor | Gil Meche | Jay Witasick | George Sherrill | Huston Street | 754 | 702 | 52 |
| 2006-09-28 | @ ANA | 159 | L 0-2 | 92-67 | 1 | 41,944 | Barry Zito | John Lackey | John Lackey | Barry Zito | Francisco Rodriguez | 754 | 704 | 50 |
| 2006-09-29 | @ ANA | 160 | L 0-6 | 92-68 | 1 | 43,948 | Esteban Loaiza | Ervin Santana | Ervin Santana | Esteban Loaiza | | 754 | 710 | 44 |
| 2006-09-30 | @ ANA | 161 | L 6-7 | 92-69 | 1 | 43,944 | Dan Haren | Joe Saunders | Hector Carrasco | Ron Flores | Francisco Rodriguez | 760 | 717 | 43 |
| 2006-10-01 | @ ANA | 162 | W 11-10 | 93-69 | 1 | 44,107 | Rich Harden | Dustin Moseley | Chad Gaudin | Chris Bootcheck | Ron Flores | 771 | 727 | 44 |