| 2010-04-05 | @ KCA | 1 | W 8-4 | 1-0 | 2 | 40,052 | Justin Verlander | Zack Greinke | Joel Zumaya | Rob Tejeda | | 8 | 4 | 4 |
| 2010-04-07 | @ KCA | 2 | L 2-3 | 1-1 | 4 | 10,574 | Max Scherzer | Luke Hochevar | Kyle Farnsworth | Jose Valverde | | 10 | 7 | 3 |
| 2010-04-08 | @ KCA | 3 | W 7-3 | 2-1 | 3 | 10,909 | Dontrelle Willis | Brian Bannister | Eddie Bonine | Luis Mendoza | | 17 | 10 | 7 |
| 2010-04-09 | vs CLE | 4 | W 5-2 | 3-1 | 2 | 45,010 | Rick Porcello | David Huff | Rick Porcello | David Huff | Jose Valverde | 22 | 12 | 10 |
| 2010-04-10 | vs CLE | 5 | W 4-2 | 4-1 | 2 | 35,332 | Jeremy Bonderman | Mitch Talbot | Jeremy Bonderman | Mitch Talbot | Ryan Perry | 26 | 14 | 12 |
| 2010-04-11 | vs CLE | 6 | W 9-8 | 5-1 | 1 | 26,081 | Justin Verlander | Jake Westbrook | Phil Coke | Chris Perez | | 35 | 22 | 13 |
| 2010-04-12 | vs KCA | 7 | L 5-10 | 6-1 | 1 | 17,058 | Max Scherzer | Luke Hochevar | Luke Hochevar | Max Scherzer | | 40 | 32 | 8 |
| 2010-04-13 | vs KCA | 8 | W 6-5 | 7-1 | 1 | 18,414 | Dontrelle Willis | Brian Bannister | Joel Zumaya | Dusty Hughes | Jose Valverde | 46 | 37 | 9 |
| 2010-04-14 | vs KCA | 9 | L 3-7 | 7-2 | 1 | 19,262 | Rick Porcello | Kyle Davies | Kyle Davies | Ryan Perry | Joakim Soria | 49 | 44 | 5 |
| 2010-04-16 | @ SEA | 10 | L 3-11 | 8-2 | 1 | 39,999 | Jeremy Bonderman | Felix Hernandez | Felix Hernandez | Jeremy Bonderman | | 52 | 55 | -3 |
| 2010-04-17 | @ SEA | 11 | L 2-4 | 8-3 | 1 | 31,647 | Justin Verlander | Ryan Rowland-Smith | Brandon League | Justin Verlander | David Aardsma | 54 | 59 | -5 |
| 2010-04-18 | @ SEA | 12 | W 4-2 | 9-3 | 1 | 30,419 | Max Scherzer | Ian Snell | Max Scherzer | Ian Snell | Jose Valverde | 58 | 61 | -3 |
| 2010-04-19 | @ ANA | 13 | L 0-2 | 9-4 | 1 | 36,006 | Dontrelle Willis | Joel Pineiro | Joel Pineiro | Dontrelle Willis | Fernando Rodney | 58 | 63 | -5 |
| 2010-04-20 | @ ANA | 14 | L 5-6 | 9-5 | 2 | 35,266 | Rick Porcello | Scott Kazmir | Scott Kazmir | Rick Porcello | Fernando Rodney | 63 | 69 | -6 |
| 2010-04-21 | @ ANA | 15 | W 4-3 | 10-5 | 2 | 35,279 | Jeremy Bonderman | Jered Weaver | Phil Coke | Brian Fuentes | Jose Valverde | 67 | 72 | -5 |
| 2010-04-22 | @ ANA | 16 | W 5-4 | 11-5 | 1 | 37,338 | Justin Verlander | Joe Saunders | Justin Verlander | Joe Saunders | Jose Valverde | 72 | 76 | -4 |
| 2010-04-23 | @ TEX | 17 | L 4-5 | 11-6 | 2 | 26,445 | Max Scherzer | Rich Harden | Neftali Feliz | Fu-Te Ni | | 76 | 81 | -5 |
| 2010-04-24 | @ TEX | 18 | W 8-4 | 12-6 | 2 | 45,752 | Brad Thomas | Scott Feldman | Eddie Bonine | Scott Feldman | | 84 | 85 | -1 |
| 2010-04-25 | @ TEX | 19 | L 4-8 | 12-7 | 2 | 31,211 | Rick Porcello | Colby Lewis | Colby Lewis | Rick Porcello | | 88 | 93 | -5 |
| 2010-04-26 | @ TEX | 20 | W 8-6 | 13-7 | 2 | 16,381 | Jeremy Bonderman | Matt Harrison | Phil Coke | Neftali Feliz | Jose Valverde | 96 | 99 | -3 |
| 2010-04-27 | vs MIN | 21 | L 0-2 | 13-8 | 2 | 22,008 | Justin Verlander | Francisco Liriano | Francisco Liriano | Justin Verlander | Jon Rauch | 96 | 101 | -5 |
| 2010-04-28 | vs MIN | 22 | W 11-6 | 13-9 | 2 | 19,900 | Max Scherzer | Scott Baker | Brad Thomas | Ron Mahay | | 107 | 107 | 0 |
| 2010-04-29 | vs MIN | 23 | W 3-0 | 14-9 | 2 | 25,595 | Dontrelle Willis | Carl Pavano | Dontrelle Willis | Carl Pavano | Jose Valverde | 110 | 107 | 3 |
| 2010-04-30 | vs ANA | 24 | W 10-6 | 14-10 | 2 | 31,725 | Rick Porcello | Joel Pineiro | Rick Porcello | Joel Pineiro | | 120 | 113 | 7 |
| 2010-05-01 | vs ANA | 25 | W 3-2 | 15-10 | 2 | 31,042 | Jeremy Bonderman | Scott Kazmir | Ryan Perry | Scot Shields | | 123 | 115 | 8 |
| 2010-05-02 | vs ANA | 26 | W 5-1 | 16-10 | 2 | 25,603 | Justin Verlander | Jered Weaver | Justin Verlander | Jered Weaver | | 128 | 116 | 12 |
| 2010-05-03 | @ MIN | 27 | L 4-10 | 17-10 | 2 | 38,728 | Max Scherzer | Scott Baker | Scott Baker | Max Scherzer | | 132 | 126 | 6 |
| 2010-05-04 | @ MIN | 28 | L 3-4 | 17-11 | 2 | 39,020 | Dontrelle Willis | Nick Blackburn | Nick Blackburn | Ryan Perry | | 135 | 130 | 5 |
| 2010-05-05 | @ MIN | 29 | L 4-5 | 17-12 | 2 | 39,037 | Rick Porcello | Kevin Slowey | Kevin Slowey | Rick Porcello | Jon Rauch | 139 | 135 | 4 |
| 2010-05-08 | @ CLE | 30 | W 6-4 | 18-12 | 3 | 18,428 | Justin Verlander | Justin Masterson | Justin Verlander | Kerry Wood | Jose Valverde | 145 | 139 | 6 |
| 2010-05-09 | @ CLE | 31 | L 4-7 | 18-13 | 2 | 16,980 | Max Scherzer | Mitch Talbot | Mitch Talbot | Max Scherzer | Chris Perez | 149 | 146 | 3 |
| 2010-05-10 | vs NYA | 32 | W 5-4 | 19-13 | 2 | 34,365 | Brad Thomas | Sergio Mitre | Eddie Bonine | Sergio Mitre | Jose Valverde | 154 | 150 | 4 |
| 2010-05-12 | vs NYA | 33 | W 2-0 | 20-14 | 3 | 27,376 | Rick Porcello | Javier Vazquez | Rick Porcello | Javier Vazquez | Jose Valverde | 156 | 150 | 6 |
| 2010-05-12 | vs NYA | 34 | L 0-8 | 20-14 | 3 | 28,514 | Jeremy Bonderman | Phil Hughes | Phil Hughes | Jeremy Bonderman | | 156 | 158 | -2 |
| 2010-05-13 | vs NYA | 35 | W 6-0 | 21-14 | 2 | 31,130 | Justin Verlander | CC Sabathia | Justin Verlander | CC Sabathia | | 162 | 158 | 4 |
| 2010-05-14 | vs BOS | 36 | L 2-7 | 21-15 | 2 | 31,732 | Max Scherzer | Clay Buchholz | Clay Buchholz | Max Scherzer | | 164 | 165 | -1 |
| 2010-05-15 | vs BOS | 37 | W 7-6 | 22-15 | 2 | 40,742 | Dontrelle Willis | Jon Lester | Jose Valverde | Manny Delcarmen | | 171 | 171 | 0 |
| 2010-05-16 | vs BOS | 38 | W 5-1 | 23-15 | 2 | 35,454 | Armando Galarraga | John Lackey | Armando Galarraga | John Lackey | | 176 | 172 | 4 |
| 2010-05-18 | vs CHA | 39 | L 2-6 | 23-16 | 2 | 28,155 | Rick Porcello | Freddy Garcia | Freddy Garcia | Rick Porcello | | 178 | 178 | 0 |
| 2010-05-19 | @ OAK | 40 | W 5-1 | 24-16 | 2 | 19,284 | Justin Verlander | Dallas Braden | Justin Verlander | Dallas Braden | | 183 | 179 | 4 |
| 2010-05-20 | @ OAK | 41 | W 5-2 | 25-16 | 1 | 24,146 | Jeremy Bonderman | Tyson Ross | Jeremy Bonderman | Tyson Ross | Jose Valverde | 188 | 181 | 7 |
| 2010-05-21 | @ LAN | 42 | L 1-4 | 25-17 | 1 | 44,282 | Dontrelle Willis | Chad Billingsley | Chad Billingsley | Dontrelle Willis | Jonathan Broxton | 189 | 185 | 4 |
| 2010-05-22 | @ LAN | 43 | L 4-6 | 25-18 | 2 | 45,117 | Armando Galarraga | John Ely | John Ely | Armando Galarraga | Jonathan Broxton | 193 | 191 | 2 |
| 2010-05-23 | @ LAN | 44 | W 6-2 | 26-18 | 1 | 46,053 | Rick Porcello | Hiroki Kuroda | Rick Porcello | Hiroki Kuroda | | 199 | 193 | 6 |
| 2010-05-25 | @ SEA | 45 | L 3-5 | 26-19 | 1 | 20,920 | Justin Verlander | Doug Fister | Shawn Kelley | Justin Verlander | David Aardsma | 202 | 198 | 4 |
| 2010-05-26 | @ SEA | 46 | L 4-5 | 26-20 | 1 | 22,422 | Jeremy Bonderman | Jason Vargas | Brandon League | Ryan Perry | David Aardsma | 206 | 203 | 3 |
| 2010-05-28 | vs OAK | 47 | L 4-5 | 26-21 | 2 | 40,210 | Dontrelle Willis | Ben Sheets | Brad Ziegler | Ryan Perry | Andrew Bailey | 210 | 208 | 2 |
| 2010-05-29 | vs OAK | 48 | L 0-6 | 26-22 | 2 | 39,750 | Rick Porcello | Brett Anderson | Brett Anderson | Rick Porcello | | 210 | 214 | -4 |
| 2010-05-30 | vs OAK | 49 | W 10-2 | 26-23 | 2 | 32,510 | Max Scherzer | Dallas Braden | Max Scherzer | Dallas Braden | Joel Zumaya | 220 | 216 | 4 |
| 2010-05-31 | vs OAK | 50 | L 1-4 | 26-24 | 2 | 23,641 | Justin Verlander | Trevor Cahill | Trevor Cahill | Justin Verlander | Andrew Bailey | 221 | 220 | 1 |
| 2010-06-01 | vs CLE | 51 | L 2-3 | 26-25 | 2 | 19,446 | Jeremy Bonderman | Jake Westbrook | Jake Westbrook | Jeremy Bonderman | Kerry Wood | 223 | 223 | 0 |
| 2010-06-02 | vs CLE | 52 | W 3-0 | 27-25 | 2 | 17,738 | Armando Galarraga | Fausto Carmona | Armando Galarraga | Fausto Carmona | | 226 | 223 | 3 |
| 2010-06-03 | vs CLE | 53 | W 12-6 | 27-26 | 2 | 28,169 | Rick Porcello | David Huff | Brad Thomas | Hector Ambriz | | 238 | 229 | 9 |
| 2010-06-04 | @ KCA | 54 | L 3-7 | 27-27 | 2 | 21,930 | Max Scherzer | Bruce Chen | Bruce Chen | Max Scherzer | | 241 | 236 | 5 |
| 2010-06-05 | @ KCA | 55 | W 4-2 | 28-27 | 2 | 24,383 | Justin Verlander | Luke Hochevar | Justin Verlander | Luke Hochevar | Jose Valverde | 245 | 238 | 7 |
| 2010-06-06 | @ KCA | 56 | L 2-7 | 28-28 | 2 | 22,240 | Jeremy Bonderman | Brian Bannister | Brian Bannister | Jeremy Bonderman | | 247 | 245 | 2 |
| 2010-06-08 | @ CHA | 57 | W 7-2 | 29-28 | 2 | 20,776 | Armando Galarraga | Gavin Floyd | Brad Thomas | Matt Thornton | | 254 | 247 | 7 |
| 2010-06-09 | @ CHA | 58 | L 3-15 | 30-28 | 2 | 21,959 | Rick Porcello | Freddy Garcia | Freddy Garcia | Rick Porcello | | 257 | 262 | -5 |
| 2010-06-10 | @ CHA | 59 | L 0-3 | 30-29 | 2 | 26,004 | Max Scherzer | John Danks | John Danks | Max Scherzer | Bobby Jenks | 257 | 265 | -8 |
| 2010-06-11 | vs PIT | 60 | W 6-2 | 31-29 | 2 | 33,236 | Justin Verlander | Ross Ohlendorf | Justin Verlander | Ross Ohlendorf | | 263 | 267 | -4 |
| 2010-06-12 | vs PIT | 61 | W 4-3 | 32-29 | 2 | 34,501 | Jeremy Bonderman | Paul Maholm | Phil Coke | Brendan Donnelly | | 267 | 270 | -3 |
| 2010-06-13 | vs PIT | 62 | W 4-3 | 33-29 | 2 | 31,243 | Armando Galarraga | Jeff Karstens | Brad Thomas | Javier Lopez | Jose Valverde | 271 | 273 | -2 |
| 2010-06-15 | vs WAS | 63 | W 7-4 | 34-29 | 2 | 24,821 | Max Scherzer | John Lannan | Max Scherzer | John Lannan | Jose Valverde | 278 | 277 | 1 |
| 2010-06-16 | vs WAS | 64 | W 8-3 | 35-29 | 2 | 24,767 | Justin Verlander | Livan Hernandez | Justin Verlander | Livan Hernandez | | 286 | 280 | 6 |
| 2010-06-17 | vs WAS | 65 | W 8-3 | 36-29 | 2 | 33,630 | Jeremy Bonderman | Luis Atilano | Jeremy Bonderman | Luis Atilano | | 294 | 283 | 11 |
| 2010-06-18 | vs ARI | 66 | W 7-5 | 37-29 | 2 | 37,438 | Armando Galarraga | Dontrelle Willis | Phil Coke | Chad Qualls | Jose Valverde | 301 | 288 | 13 |
| 2010-06-19 | vs ARI | 67 | L 5-6 | 37-30 | 2 | 40,681 | Rick Porcello | Edwin Jackson | Edwin Jackson | Rick Porcello | Aaron Heilman | 306 | 294 | 12 |
| 2010-06-20 | vs ARI | 68 | W 3-1 | 38-30 | 2 | 41,417 | Max Scherzer | Ian Kennedy | Max Scherzer | Ian Kennedy | Jose Valverde | 309 | 295 | 14 |
| 2010-06-22 | @ NYN | 69 | L 6-14 | 39-30 | 2 | 32,363 | Justin Verlander | Jonathon Niese | Fernando Nieve | Justin Verlander | | 315 | 309 | 6 |
| 2010-06-23 | @ NYN | 70 | L 0-5 | 39-31 | 2 | 35,045 | Jeremy Bonderman | R.A. Dickey | R.A. Dickey | Jeremy Bonderman | | 315 | 314 | 1 |
| 2010-06-24 | @ NYN | 71 | W 6-5 | 40-31 | 1 | 31,319 | Armando Galarraga | Hisanori Takahashi | Armando Galarraga | Hisanori Takahashi | Jose Valverde | 321 | 319 | 2 |
| 2010-06-25 | @ ATL | 72 | L 1-3 | 40-32 | 1 | 36,634 | Andrew Oliver | Kris Medlen | Kris Medlen | Andrew Oliver | Billy Wagner | 322 | 322 | 0 |
| 2010-06-26 | @ ATL | 73 | L 3-4 | 40-33 | 2 | 39,184 | Max Scherzer | Kenshin Kawakami | Kenshin Kawakami | Joel Zumaya | Peter Moylan | 325 | 326 | -1 |
| 2010-06-27 | @ ATL | 74 | W 10-4 | 40-34 | 2 | 26,034 | Justin Verlander | Tommy Hanson | Justin Verlander | Tommy Hanson | | 335 | 330 | 5 |
| 2010-06-28 | @ MIN | 75 | W 7-5 | 41-34 | 1 | 40,681 | Jeremy Bonderman | Francisco Liriano | Jeremy Bonderman | Francisco Liriano | Jose Valverde | 342 | 335 | 7 |
| 2010-06-29 | @ MIN | 76 | L 4-11 | 42-34 | 1 | 40,593 | Armando Galarraga | Nick Blackburn | Nick Blackburn | Armando Galarraga | | 346 | 346 | 0 |
| 2010-06-30 | @ MIN | 77 | L 1-5 | 42-35 | 1 | 40,671 | Andrew Oliver | Kevin Slowey | Kevin Slowey | Andrew Oliver | | 347 | 351 | -4 |
| 2010-07-02 | vs SEA | 78 | W 7-1 | 43-35 | 1 | 32,512 | Max Scherzer | Doug Fister | Max Scherzer | Doug Fister | | 354 | 352 | 2 |
| 2010-07-03 | vs SEA | 79 | W 6-1 | 44-35 | 1 | 32,430 | Justin Verlander | Jason Vargas | Justin Verlander | Jason Vargas | | 360 | 353 | 7 |
| 2010-07-04 | vs SEA | 80 | L 1-8 | 44-36 | 1 | 24,899 | Jeremy Bonderman | Cliff Lee | Cliff Lee | Jeremy Bonderman | | 361 | 361 | 0 |
| 2010-07-05 | vs BAL | 81 | W 12-9 | 44-37 | 1 | 26,432 | Andrew Oliver | Kevin Millwood | Eddie Bonine | Mark Hendrickson | | 373 | 370 | 3 |
| 2010-07-06 | vs BAL | 82 | W 7-5 | 45-37 | 1 | 22,532 | Armando Galarraga | Jake Arrieta | Ryan Perry | David Hernandez | | 380 | 375 | 5 |
| 2010-07-07 | vs BAL | 83 | W 4-2 | 46-37 | 1 | 22,837 | Max Scherzer | Brad Bergesen | Max Scherzer | Brad Bergesen | Phil Coke | 384 | 377 | 7 |
| 2010-07-09 | vs MIN | 84 | W 7-3 | 47-37 | 1 | 42,549 | Justin Verlander | Francisco Liriano | Justin Verlander | Francisco Liriano | | 391 | 380 | 11 |
| 2010-07-10 | vs MIN | 85 | W 7-4 | 48-37 | 1 | 41,461 | Jeremy Bonderman | Nick Blackburn | Jeremy Bonderman | Nick Blackburn | Jose Valverde | 398 | 384 | 14 |
| 2010-07-11 | vs MIN | 86 | L 3-6 | 48-38 | 1 | 39,689 | Andrew Oliver | Carl Pavano | Carl Pavano | Andrew Oliver | Jon Rauch | 401 | 390 | 11 |
| 2010-07-16 | @ CLE | 87 | L 2-8 | 48-39 | 1 | 22,295 | Max Scherzer | Jake Westbrook | Jake Westbrook | Max Scherzer | | 403 | 398 | 5 |
| 2010-07-17 | @ CLE | 88 | L 3-4 | 48-41 | 3 | 20,090 | Justin Verlander | Fausto Carmona | Fausto Carmona | Phil Coke | Chris Perez | 406 | 402 | 4 |
| 2010-07-17 | @ CLE | 89 | L 1-2 | 48-41 | 3 | 20,902 | Rick Porcello | Mitch Talbot | Rafael Perez | Robbie Weinhart | | 407 | 404 | 3 |
| 2010-07-18 | @ CLE | 90 | L 2-7 | 48-42 | 2 | 19,102 | Andrew Oliver | Jeanmar Gomez | Jeanmar Gomez | Andrew Oliver | | 409 | 411 | -2 |
| 2010-07-19 | vs TEX | 91 | L 6-8 | 48-43 | 2 | 26,626 | Jeremy Bonderman | Scott Feldman | Matt Harrison | Enrique Gonzalez | Neftali Feliz | 415 | 419 | -4 |
| 2010-07-20 | vs TEX | 92 | L 0-8 | 48-44 | 2 | 27,576 | Armando Galarraga | Tommy Hunter | Tommy Hunter | Armando Galarraga | | 415 | 427 | -12 |
| 2010-07-21 | vs TEX | 93 | W 4-1 | 49-44 | 2 | 28,704 | Max Scherzer | Colby Lewis | Max Scherzer | Colby Lewis | | 419 | 428 | -9 |
| 2010-07-22 | vs TOR | 94 | W 5-2 | 50-44 | 2 | 34,476 | Justin Verlander | Ricky Romero | Justin Verlander | Ricky Romero | Jose Valverde | 424 | 430 | -6 |
| 2010-07-24 | vs TOR | 95 | L 2-3 | 50-45 | 3 | 39,391 | Rick Porcello | Shaun Marcum | Shaun Marcum | Rick Porcello | Kevin Gregg | 426 | 433 | -7 |
| 2010-07-25 | vs TOR | 96 | L 3-5 | 50-46 | 4 | 38,526 | Armando Galarraga | Brett Cecil | Scott Downs | Jose Valverde | Kevin Gregg | 429 | 438 | -9 |
| 2010-07-25 | vs TOR | 97 | W 6-5 | 50-46 | 4 | 37,093 | Jeremy Bonderman | Jesse Litsch | Phil Coke | Jason Frasor | Jose Valverde | 435 | 443 | -8 |
| 2010-07-26 | @ TBA | 98 | L 0-5 | 51-47 | 3 | 17,009 | Max Scherzer | Matt Garza | Matt Garza | Max Scherzer | | 435 | 448 | -13 |
| 2010-07-27 | @ TBA | 99 | L 2-3 | 51-48 | 3 | 19,843 | Justin Verlander | James Shields | James Shields | Justin Verlander | Rafael Soriano | 437 | 451 | -14 |
| 2010-07-28 | @ TBA | 100 | L 4-7 | 51-49 | 3 | 16,209 | Eddie Bonine | Jeff Niemann | Jeff Niemann | Eddie Bonine | Rafael Soriano | 441 | 458 | -17 |
| 2010-07-29 | @ TBA | 101 | L 2-4 | 51-50 | 3 | 26,716 | Rick Porcello | David Price | David Price | Rick Porcello | Dan Wheeler | 443 | 462 | -19 |
| 2010-07-30 | @ BOS | 102 | W 6-5 | 52-50 | 3 | 37,832 | Armando Galarraga | Jon Lester | Robbie Weinhart | Jon Lester | | 449 | 467 | -18 |
| 2010-07-31 | @ BOS | 103 | L 4-5 | 52-51 | 3 | 37,498 | Max Scherzer | Daisuke Matsuzaka | Hideki Okajima | Phil Coke | | 453 | 472 | -19 |
| 2010-08-01 | @ BOS | 104 | L 3-4 | 52-52 | 3 | 37,479 | Justin Verlander | Clay Buchholz | Jonathan Papelbon | Brad Thomas | | 456 | 476 | -20 |
| 2010-08-03 | vs CHA | 105 | L 2-12 | 53-52 | 5 | 26,141 | Rick Porcello | Mark Buehrle | Mark Buehrle | Rick Porcello | | 458 | 488 | -30 |
| 2010-08-03 | vs CHA | 106 | W 7-1 | 53-52 | 5 | 24,826 | Jeremy Bonderman | Carlos Torres | Jeremy Bonderman | Carlos Torres | | 465 | 489 | -24 |
| 2010-08-04 | vs CHA | 107 | L 1-4 | 54-53 | 3 | 31,770 | Armando Galarraga | Edwin Jackson | Edwin Jackson | Armando Galarraga | Bobby Jenks | 466 | 493 | -27 |
| 2010-08-05 | vs CHA | 108 | L 4-6 | 54-54 | 3 | 34,156 | Max Scherzer | Freddy Garcia | Sergio Santos | Jose Valverde | | 470 | 499 | -29 |
| 2010-08-06 | vs ANA | 109 | L 2-4 | 54-55 | 3 | 35,106 | Justin Verlander | Jered Weaver | Jered Weaver | Justin Verlander | Brian Fuentes | 472 | 503 | -31 |
| 2010-08-07 | vs ANA | 110 | L 1-10 | 54-56 | 3 | 38,783 | Jeremy Bonderman | Scott Kazmir | Scott Kazmir | Jeremy Bonderman | | 473 | 513 | -40 |
| 2010-08-08 | vs ANA | 111 | W 9-4 | 55-56 | 3 | 32,037 | Rick Porcello | Trevor Bell | Rick Porcello | Trevor Bell | | 482 | 517 | -35 |
| 2010-08-09 | vs TBA | 112 | L 3-6 | 55-57 | 3 | 23,932 | Armando Galarraga | David Price | David Price | Armando Galarraga | Rafael Soriano | 485 | 523 | -38 |
| 2010-08-10 | vs TBA | 113 | L 0-8 | 55-58 | 3 | 26,114 | Max Scherzer | Jeremy Hellickson | Jeremy Hellickson | Max Scherzer | | 485 | 531 | -46 |
| 2010-08-11 | vs TBA | 114 | W 3-2 | 56-58 | 3 | 28,815 | Justin Verlander | Matt Garza | Justin Verlander | Matt Garza | Jose Valverde | 488 | 533 | -45 |
| 2010-08-13 | @ CHA | 115 | L 4-8 | 56-59 | 3 | 34,834 | Jeremy Bonderman | Mark Buehrle | Mark Buehrle | Jeremy Bonderman | | 492 | 541 | -49 |
| 2010-08-14 | @ CHA | 116 | W 3-2 | 57-59 | 3 | 36,548 | Rick Porcello | Edwin Jackson | Phil Coke | J.J. Putz | | 495 | 543 | -48 |
| 2010-08-15 | @ CHA | 117 | W 13-8 | 57-60 | 3 | 36,287 | Armando Galarraga | Freddy Garcia | Brad Thomas | J.J. Putz | | 508 | 551 | -43 |
| 2010-08-16 | @ NYA | 118 | W 3-1 | 58-60 | 3 | 46,098 | Max Scherzer | Javier Vazquez | Max Scherzer | Javier Vazquez | Jose Valverde | 511 | 552 | -41 |
| 2010-08-17 | @ NYA | 119 | L 2-6 | 58-61 | 3 | 46,906 | Justin Verlander | CC Sabathia | CC Sabathia | Justin Verlander | | 513 | 558 | -45 |
| 2010-08-18 | @ NYA | 120 | L 5-9 | 58-62 | 3 | 46,479 | Jeremy Bonderman | Dustin Moseley | Dustin Moseley | Jeremy Bonderman | | 518 | 567 | -49 |
| 2010-08-19 | @ NYA | 121 | L 5-11 | 59-62 | 3 | 48,143 | Rick Porcello | Phil Hughes | Phil Hughes | Rick Porcello | Sergio Mitre | 523 | 578 | -55 |
| 2010-08-20 | vs CLE | 122 | W 6-0 | 60-62 | 3 | 33,936 | Armando Galarraga | Justin Masterson | Armando Galarraga | Justin Masterson | | 529 | 578 | -49 |
| 2010-08-21 | vs CLE | 123 | W 5-2 | 61-62 | 4 | 38,088 | Max Scherzer | Josh Tomlin | Max Scherzer | Josh Tomlin | Jose Valverde | 534 | 580 | -46 |
| 2010-08-22 | vs CLE | 124 | W 8-1 | 62-62 | 3 | 35,104 | Justin Verlander | Jeanmar Gomez | Justin Verlander | Jeanmar Gomez | | 542 | 581 | -39 |
| 2010-08-23 | vs KCA | 125 | W 12-3 | 62-63 | 3 | 30,552 | Jeremy Bonderman | Bruce Chen | Jeremy Bonderman | Bruce Chen | | 554 | 584 | -30 |
| 2010-08-24 | vs KCA | 126 | W 9-1 | 63-63 | 3 | 29,043 | Rick Porcello | Kyle Davies | Rick Porcello | Kyle Davies | | 563 | 585 | -22 |
| 2010-08-25 | vs KCA | 127 | L 3-4 | 63-64 | 3 | 31,231 | Armando Galarraga | Sean O'Sullivan | Philip Humber | Alfredo Figaro | Joakim Soria | 566 | 589 | -23 |
| 2010-08-26 | @ TOR | 128 | W 7-1 | 64-64 | 3 | 16,088 | Max Scherzer | Ricky Romero | Max Scherzer | Ricky Romero | | 573 | 590 | -17 |
| 2010-08-27 | @ TOR | 129 | L 2-3 | 64-65 | 3 | 20,298 | Justin Verlander | Shaun Marcum | Shawn Camp | Phil Coke | | 575 | 593 | -18 |
| 2010-08-28 | @ TOR | 130 | L 4-5 | 64-66 | 3 | 27,119 | Alfredo Figaro | Brandon Morrow | Brandon Morrow | Alfredo Figaro | Kevin Gregg | 579 | 598 | -19 |
| 2010-08-29 | @ TOR | 131 | W 10-4 | 64-67 | 3 | 26,624 | Rick Porcello | Marc Rzepczynski | Rick Porcello | Marc Rzepczynski | | 589 | 602 | -13 |
| 2010-08-31 | @ MIN | 132 | L 3-4 | 64-68 | 3 | 40,186 | Armando Galarraga | Brian Duensing | Matt Guerrier | Phil Coke | Matt Capps | 592 | 606 | -14 |
| 2010-09-01 | @ MIN | 133 | L 1-2 | 64-69 | 3 | 39,438 | Max Scherzer | Francisco Liriano | Jon Rauch | Ryan Perry | | 593 | 608 | -15 |
| 2010-09-02 | @ MIN | 134 | W 10-9 | 64-70 | 3 | 39,551 | Justin Verlander | Scott Baker | Jose Valverde | Nick Blackburn | | 603 | 617 | -14 |
| 2010-09-03 | @ KCA | 135 | W 9-5 | 65-70 | 3 | 17,835 | Jeremy Bonderman | Zack Greinke | Ryan Perry | Jesse Chavez | | 612 | 622 | -10 |
| 2010-09-04 | @ KCA | 136 | W 6-4 | 66-70 | 4 | 21,483 | Rick Porcello | Bruce Chen | Rick Porcello | Dusty Hughes | Jose Valverde | 618 | 626 | -8 |
| 2010-09-05 | @ KCA | 137 | L 1-2 | 66-71 | 3 | 19,061 | Armando Galarraga | Kyle Davies | Kyle Davies | Brad Thomas | Joakim Soria | 619 | 628 | -9 |
| 2010-09-06 | vs CHA | 138 | L 4-5 | 66-72 | 3 | 32,924 | Max Scherzer | Edwin Jackson | Chris Sale | Jose Valverde | | 623 | 633 | -10 |
| 2010-09-07 | vs CHA | 139 | W 9-1 | 67-72 | 3 | 24,905 | Justin Verlander | Freddy Garcia | Justin Verlander | Freddy Garcia | | 632 | 634 | -2 |
| 2010-09-08 | vs CHA | 140 | W 5-1 | 68-72 | 3 | 25,995 | Jeremy Bonderman | John Danks | Jeremy Bonderman | John Danks | | 637 | 635 | 2 |
| 2010-09-09 | vs CHA | 141 | W 6-3 | 69-72 | 3 | 29,995 | Rick Porcello | Gavin Floyd | Rick Porcello | Gavin Floyd | Ryan Perry | 643 | 638 | 5 |
| 2010-09-10 | vs BAL | 142 | L 3-6 | 69-73 | 3 | 28,575 | Armando Galarraga | Kevin Millwood | David Hernandez | Phil Coke | Koji Uehara | 646 | 644 | 2 |
| 2010-09-11 | vs BAL | 143 | L 3-5 | 69-74 | 3 | 28,139 | Max Scherzer | Jeremy Guthrie | Jeremy Guthrie | Max Scherzer | Koji Uehara | 649 | 649 | 0 |
| 2010-09-12 | vs BAL | 144 | W 6-2 | 70-74 | 3 | 24,170 | Justin Verlander | Chris Tillman | Justin Verlander | Mike Gonzalez | | 655 | 651 | 4 |
| 2010-09-14 | @ TEX | 145 | L 4-11 | 71-74 | 3 | 24,452 | Jeremy Bonderman | Derek Holland | Dustin Nippert | Robbie Weinhart | | 659 | 662 | -3 |
| 2010-09-15 | @ TEX | 146 | L 7-11 | 72-74 | 3 | 34,964 | Armando Galarraga | Colby Lewis | Colby Lewis | Armando Galarraga | | 666 | 673 | -7 |
| 2010-09-17 | @ CHA | 147 | W 9-2 | 73-74 | 3 | 28,563 | Max Scherzer | Edwin Jackson | Max Scherzer | Edwin Jackson | | 675 | 675 | 0 |
| 2010-09-18 | @ CHA | 148 | W 6-3 | 74-74 | 3 | 27,828 | Justin Verlander | Lucas Harrell | Justin Verlander | Sergio Santos | | 681 | 678 | 3 |
| 2010-09-19 | @ CHA | 149 | W 9-7 | 75-74 | 3 | 25,417 | Jeremy Bonderman | John Danks | Robbie Weinhart | Sergio Santos | Daniel Schlereth | 690 | 685 | 5 |
| 2010-09-20 | vs KCA | 150 | W 7-5 | 76-74 | 3 | 24,382 | Rick Porcello | Zack Greinke | Brad Thomas | Zack Greinke | Phil Coke | 697 | 690 | 7 |
| 2010-09-21 | vs KCA | 151 | L 6-9 | 76-75 | 3 | 26,178 | Armando Galarraga | Bruce Chen | Bruce Chen | Armando Galarraga | Joakim Soria | 703 | 699 | 4 |
| 2010-09-22 | vs KCA | 152 | W 4-2 | 77-75 | 3 | 24,678 | Max Scherzer | Kyle Davies | Max Scherzer | Kyle Davies | | 707 | 701 | 6 |
| 2010-09-24 | vs MIN | 153 | W 10-1 | 78-75 | 3 | 30,083 | Justin Verlander | Francisco Liriano | Justin Verlander | Francisco Liriano | | 717 | 702 | 15 |
| 2010-09-25 | vs MIN | 154 | W 11-10 | 79-75 | 3 | 34,129 | Jeremy Bonderman | Carl Pavano | Daniel Schlereth | Pat Neshek | | 728 | 712 | 16 |
| 2010-09-26 | vs MIN | 155 | W 5-1 | 80-75 | 3 | 32,021 | Rick Porcello | Brian Duensing | Rick Porcello | Brian Duensing | | 733 | 713 | 20 |
| 2010-09-27 | @ CLE | 156 | L 3-6 | 80-76 | 3 | 10,161 | Armando Galarraga | Carlos Carrasco | Carlos Carrasco | Armando Galarraga | Chris Perez | 736 | 719 | 17 |
| 2010-09-29 | @ CLE | 157 | L 0-4 | 80-78 | 4 | 0 | Max Scherzer | Mitch Talbot | Mitch Talbot | Max Scherzer | | 736 | 723 | 13 |
| 2010-09-29 | @ CLE | 158 | L 3-4 | 80-78 | 4 | 12,227 | Justin Verlander | Josh Tomlin | Josh Tomlin | Justin Verlander | Chris Perez | 739 | 727 | 12 |
| 2010-10-01 | @ BAL | 159 | L 6-10 | 81-79 | 4 | 0 | Jeremy Bonderman | Chris Tillman | Chris Tillman | Jeremy Bonderman | | 745 | 737 | 8 |
| 2010-10-01 | @ BAL | 160 | L 1-2 | 81-79 | 4 | 20,870 | Rick Porcello | Jeremy Guthrie | Jeremy Guthrie | Rick Porcello | Koji Uehara | 746 | 739 | 7 |
| 2010-10-02 | @ BAL | 161 | L 1-2 | 81-80 | 3 | 35,332 | Armando Galarraga | Brian Matusz | Brian Matusz | Armando Galarraga | Koji Uehara | 747 | 741 | 6 |
| 2010-10-03 | @ BAL | 162 | W 4-2 | 82-80 | 3 | 23,914 | Phil Coke | Brad Bergesen | Daniel Schlereth | Brad Bergesen | Jose Valverde | 751 | 743 | 8 |