| 2010-04-04 | vs NYA | 1 | W 9-7 | 1-0 | 1 | 37,440 | Josh Beckett | CC Sabathia | Hideki Okajima | Chan Ho Park | Jonathan Papelbon | 9 | 7 | 2 |
| 2010-04-06 | vs NYA | 2 | L 4-6 | 1-1 | 2 | 38,000 | Jon Lester | A.J. Burnett | Alfredo Aceves | Hideki Okajima | Mariano Rivera | 13 | 13 | 0 |
| 2010-04-07 | vs NYA | 3 | L 1-3 | 1-2 | 4 | 38,238 | John Lackey | Andy Pettitte | Chan Ho Park | Jonathan Papelbon | Mariano Rivera | 14 | 16 | -2 |
| 2010-04-09 | @ KCA | 4 | L 3-4 | 1-3 | 5 | 21,091 | Tim Wakefield | Kyle Davies | John Parrish | Daniel Bard | Joakim Soria | 17 | 20 | -3 |
| 2010-04-10 | @ KCA | 5 | W 8-3 | 2-3 | 4 | 37,505 | Josh Beckett | Zack Greinke | Josh Beckett | Zack Greinke | | 25 | 23 | 2 |
| 2010-04-11 | @ KCA | 6 | W 8-6 | 3-3 | 3 | 19,240 | Clay Buchholz | Gil Meche | Clay Buchholz | Gil Meche | Jonathan Papelbon | 33 | 29 | 4 |
| 2010-04-12 | @ MIN | 7 | L 2-5 | 3-4 | 4 | 38,145 | Jon Lester | Carl Pavano | Carl Pavano | Jon Lester | Jon Rauch | 35 | 34 | 1 |
| 2010-04-14 | @ MIN | 8 | W 6-3 | 4-4 | 4 | 38,164 | John Lackey | Kevin Slowey | John Lackey | Kevin Slowey | Jonathan Papelbon | 41 | 37 | 4 |
| 2010-04-15 | @ MIN | 9 | L 0-8 | 4-5 | 4 | 38,341 | Tim Wakefield | Francisco Liriano | Francisco Liriano | Tim Wakefield | | 41 | 45 | -4 |
| 2010-04-16 | vs TBA | 10 | L 1-3 | 4-6 | 4 | 37,084 | Josh Beckett | Wade Davis | Lance Cormier | Manny Delcarmen | Rafael Soriano | 42 | 48 | -6 |
| 2010-04-17 | vs TBA | 11 | L 5-6 | 4-7 | 4 | 37,022 | Clay Buchholz | James Shields | James Shields | Clay Buchholz | Rafael Soriano | 47 | 54 | -7 |
| 2010-04-18 | vs TBA | 12 | L 1-7 | 4-8 | 4 | 37,143 | Jon Lester | Matt Garza | Matt Garza | Jon Lester | | 48 | 61 | -13 |
| 2010-04-19 | vs TBA | 13 | L 2-8 | 4-9 | 4 | 37,609 | John Lackey | Jeff Niemann | Jeff Niemann | John Lackey | | 50 | 69 | -19 |
| 2010-04-20 | vs TEX | 14 | W 7-6 | 5-9 | 4 | 37,614 | Tim Wakefield | Colby Lewis | Jonathan Papelbon | Frank Francisco | | 57 | 75 | -18 |
| 2010-04-21 | vs TEX | 15 | W 8-7 | 6-9 | 4 | 37,518 | Josh Beckett | Matt Harrison | Hideki Okajima | Dustin Nippert | | 65 | 82 | -17 |
| 2010-04-22 | vs TEX | 16 | L 0-3 | 6-10 | 4 | 37,417 | Clay Buchholz | C.J. Wilson | C.J. Wilson | Clay Buchholz | Darren Oliver | 65 | 85 | -20 |
| 2010-04-23 | vs BAL | 17 | W 4-3 | 7-10 | 4 | 37,367 | Jon Lester | Jeremy Guthrie | Manny Delcarmen | Matt Albers | Jonathan Papelbon | 69 | 88 | -19 |
| 2010-04-24 | vs BAL | 18 | W 7-6 | 8-10 | 4 | 38,017 | John Lackey | Brian Matusz | John Lackey | Matt Albers | Jonathan Papelbon | 76 | 94 | -18 |
| 2010-04-25 | vs BAL | 19 | L 6-7 | 8-11 | 4 | 37,102 | Tim Wakefield | David Hernandez | Jim Johnson | Scott Atchison | Cla Meredith | 82 | 101 | -19 |
| 2010-04-26 | @ TOR | 20 | W 13-12 | 9-11 | 4 | 13,847 | Josh Beckett | Dana Eveland | Scott Schoeneweis | Shawn Camp | Jonathan Papelbon | 95 | 113 | -18 |
| 2010-04-27 | @ TOR | 21 | W 2-1 | 10-11 | 3 | 14,776 | Clay Buchholz | Shaun Marcum | Clay Buchholz | Scott Downs | Ramon Ramirez | 97 | 114 | -17 |
| 2010-04-28 | @ TOR | 22 | W 2-0 | 11-11 | 3 | 15,276 | Jon Lester | Brett Cecil | Jon Lester | Brett Cecil | Jonathan Papelbon | 99 | 114 | -15 |
| 2010-04-30 | @ BAL | 23 | L 4-5 | 11-12 | 3 | 30,668 | John Lackey | David Hernandez | Matt Albers | Ramon Ramirez | | 103 | 119 | -16 |
| 2010-05-01 | @ BAL | 24 | L 9-12 | 12-12 | 3 | 35,164 | Daisuke Matsuzaka | Brad Bergesen | Brad Bergesen | Daisuke Matsuzaka | Alfredo Simon | 112 | 131 | -19 |
| 2010-05-02 | @ BAL | 25 | L 2-3 | 12-13 | 3 | 34,255 | Josh Beckett | Kevin Millwood | Matt Albers | Jonathan Papelbon | | 114 | 134 | -20 |
| 2010-05-03 | vs ANA | 26 | W 17-8 | 12-14 | 4 | 37,404 | Clay Buchholz | Joe Saunders | Clay Buchholz | Joe Saunders | | 131 | 142 | -11 |
| 2010-05-04 | vs ANA | 27 | W 5-1 | 13-14 | 4 | 37,411 | Jon Lester | Ervin Santana | Jon Lester | Kevin Jepsen | | 136 | 143 | -7 |
| 2010-05-05 | vs ANA | 28 | W 3-1 | 14-14 | 4 | 37,601 | John Lackey | Joel Pineiro | John Lackey | Joel Pineiro | Jonathan Papelbon | 139 | 144 | -5 |
| 2010-05-06 | vs ANA | 29 | W 11-6 | 14-15 | 4 | 37,639 | Daisuke Matsuzaka | Scott Kazmir | Daisuke Matsuzaka | Scott Kazmir | | 150 | 150 | 0 |
| 2010-05-07 | vs NYA | 30 | L 3-10 | 15-15 | 4 | 37,898 | Josh Beckett | Phil Hughes | Phil Hughes | Josh Beckett | | 153 | 160 | -7 |
| 2010-05-08 | vs NYA | 31 | L 3-14 | 16-15 | 4 | 37,138 | Clay Buchholz | CC Sabathia | Alfredo Aceves | Clay Buchholz | | 156 | 174 | -18 |
| 2010-05-09 | vs NYA | 32 | W 9-3 | 17-15 | 4 | 37,618 | Jon Lester | A.J. Burnett | Jon Lester | A.J. Burnett | | 165 | 177 | -12 |
| 2010-05-10 | vs TOR | 33 | W 7-6 | 18-15 | 3 | 37,332 | John Lackey | Brandon Morrow | John Lackey | Brandon Morrow | Jonathan Papelbon | 172 | 183 | -11 |
| 2010-05-11 | vs TOR | 34 | W 6-1 | 19-15 | 3 | 37,609 | Daisuke Matsuzaka | Dana Eveland | Daisuke Matsuzaka | Dana Eveland | | 178 | 184 | -6 |
| 2010-05-12 | vs TOR | 35 | L 2-3 | 19-16 | 4 | 37,198 | Tim Wakefield | Shaun Marcum | Shaun Marcum | Tim Wakefield | Kevin Gregg | 180 | 187 | -7 |
| 2010-05-14 | @ DET | 36 | W 7-2 | 20-16 | 3 | 31,732 | Clay Buchholz | Max Scherzer | Clay Buchholz | Max Scherzer | | 187 | 189 | -2 |
| 2010-05-15 | @ DET | 37 | L 6-7 | 20-17 | 4 | 40,742 | Jon Lester | Dontrelle Willis | Jose Valverde | Manny Delcarmen | | 193 | 196 | -3 |
| 2010-05-16 | @ DET | 38 | L 1-5 | 20-18 | 4 | 35,454 | John Lackey | Armando Galarraga | Armando Galarraga | John Lackey | | 194 | 201 | -7 |
| 2010-05-17 | @ NYA | 39 | L 9-11 | 21-18 | 4 | 48,271 | Daisuke Matsuzaka | Phil Hughes | Javier Vazquez | Jonathan Papelbon | | 203 | 212 | -9 |
| 2010-05-18 | @ NYA | 40 | W 7-6 | 22-18 | 2 | 47,734 | Josh Beckett | CC Sabathia | Daniel Bard | Mariano Rivera | Jonathan Papelbon | 210 | 218 | -8 |
| 2010-05-19 | vs MIN | 41 | W 3-2 | 23-18 | 2 | 37,426 | Clay Buchholz | Scott Baker | Clay Buchholz | Scott Baker | Daniel Bard | 213 | 220 | -7 |
| 2010-05-20 | vs MIN | 42 | W 6-2 | 24-18 | 2 | 38,144 | Jon Lester | Francisco Liriano | Jon Lester | Francisco Liriano | | 219 | 222 | -3 |
| 2010-05-21 | @ PHI | 43 | L 1-5 | 24-19 | 2 | 45,341 | John Lackey | Cole Hamels | Cole Hamels | John Lackey | J.C. Romero | 220 | 227 | -7 |
| 2010-05-22 | @ PHI | 44 | W 5-0 | 25-19 | 2 | 45,310 | Daisuke Matsuzaka | Kyle Kendrick | Daisuke Matsuzaka | Kyle Kendrick | | 225 | 227 | -2 |
| 2010-05-23 | @ PHI | 45 | W 8-3 | 26-19 | 2 | 45,068 | Tim Wakefield | Roy Halladay | Tim Wakefield | Roy Halladay | | 233 | 230 | 3 |
| 2010-05-24 | @ TBA | 46 | W 6-1 | 27-19 | 2 | 21,430 | Clay Buchholz | Wade Davis | Clay Buchholz | Wade Davis | | 239 | 231 | 8 |
| 2010-05-25 | @ TBA | 47 | W 2-0 | 28-19 | 2 | 24,310 | Jon Lester | James Shields | Jon Lester | James Shields | Jonathan Papelbon | 241 | 231 | 10 |
| 2010-05-26 | @ TBA | 48 | W 11-3 | 28-20 | 2 | 22,147 | John Lackey | Matt Garza | John Lackey | Matt Garza | | 252 | 234 | 18 |
| 2010-05-27 | vs KCA | 49 | L 3-4 | 28-21 | 2 | 37,940 | Daisuke Matsuzaka | Brian Bannister | Brian Bannister | Daisuke Matsuzaka | Joakim Soria | 255 | 238 | 17 |
| 2010-05-28 | vs KCA | 50 | L 5-12 | 29-21 | 2 | 37,945 | Tim Wakefield | Kyle Davies | Kyle Davies | Tim Wakefield | | 260 | 250 | 10 |
| 2010-05-29 | vs KCA | 51 | W 1-0 | 30-21 | 2 | 37,956 | Clay Buchholz | Zack Greinke | Clay Buchholz | Zack Greinke | Jonathan Papelbon | 261 | 250 | 11 |
| 2010-05-30 | vs KCA | 52 | W 8-1 | 31-21 | 2 | 37,581 | Jon Lester | Bruce Chen | Jon Lester | Brad Thompson | | 269 | 251 | 18 |
| 2010-06-01 | vs OAK | 53 | W 9-4 | 32-21 | 1 | 37,337 | John Lackey | Gio Gonzalez | John Lackey | Tyson Ross | | 278 | 255 | 23 |
| 2010-06-02 | vs OAK | 54 | W 6-4 | 33-21 | 1 | 37,783 | Daisuke Matsuzaka | Ben Sheets | Daisuke Matsuzaka | Ben Sheets | Jonathan Papelbon | 284 | 259 | 25 |
| 2010-06-03 | vs OAK | 55 | L 8-9 | 33-22 | 2 | 37,386 | Tim Wakefield | Brett Anderson | Vin Mazzaro | Tim Wakefield | Andrew Bailey | 292 | 268 | 24 |
| 2010-06-04 | @ BAL | 56 | W 11-0 | 34-22 | 1 | 30,070 | Clay Buchholz | Chris Tillman | Clay Buchholz | Chris Tillman | | 303 | 268 | 35 |
| 2010-06-05 | @ BAL | 57 | W 8-2 | 35-22 | 1 | 40,001 | Jon Lester | Jeremy Guthrie | Jon Lester | Jeremy Guthrie | | 311 | 270 | 41 |
| 2010-06-06 | @ BAL | 58 | L 3-4 | 35-23 | 1 | 27,774 | John Lackey | Brian Matusz | David Hernandez | Hideki Okajima | | 314 | 274 | 40 |
| 2010-06-07 | @ CLE | 59 | W 4-1 | 36-23 | 1 | 14,758 | Daisuke Matsuzaka | Fausto Carmona | Daisuke Matsuzaka | Fausto Carmona | | 318 | 275 | 43 |
| 2010-06-08 | @ CLE | 60 | W 3-2 | 37-23 | 1 | 15,462 | Tim Wakefield | David Huff | Tim Wakefield | David Huff | Daniel Bard | 321 | 277 | 44 |
| 2010-06-09 | @ CLE | 61 | L 0-11 | 37-24 | 2 | 14,022 | Clay Buchholz | Justin Masterson | Justin Masterson | Clay Buchholz | | 321 | 288 | 33 |
| 2010-06-10 | @ CLE | 62 | L 7-8 | 37-25 | 2 | 20,446 | Jon Lester | Mitch Talbot | Kerry Wood | Daniel Bard | | 328 | 296 | 32 |
| 2010-06-11 | vs PHI | 63 | W 12-2 | 37-26 | 2 | 38,021 | John Lackey | Jamie Moyer | John Lackey | Jamie Moyer | | 340 | 298 | 42 |
| 2010-06-12 | vs PHI | 64 | W 10-2 | 37-27 | 2 | 37,061 | Scott Atchison | Joe Blanton | Manny Delcarmen | Joe Blanton | | 350 | 300 | 50 |
| 2010-06-13 | vs PHI | 65 | L 3-5 | 37-28 | 2 | 37,230 | Tim Wakefield | Cole Hamels | Cole Hamels | Tim Wakefield | Brad Lidge | 353 | 305 | 48 |
| 2010-06-15 | vs ARI | 66 | W 6-3 | 38-28 | 2 | 37,459 | Clay Buchholz | Ian Kennedy | Clay Buchholz | Ian Kennedy | Jonathan Papelbon | 359 | 308 | 51 |
| 2010-06-16 | vs ARI | 67 | W 6-2 | 39-28 | 2 | 37,452 | Jon Lester | Rodrigo Lopez | Jon Lester | Rodrigo Lopez | Jonathan Papelbon | 365 | 310 | 55 |
| 2010-06-17 | vs ARI | 68 | W 8-5 | 40-28 | 1 | 37,544 | John Lackey | Dan Haren | John Lackey | Dan Haren | | 373 | 315 | 58 |
| 2010-06-18 | vs LAN | 69 | W 10-6 | 40-29 | 1 | 37,723 | Felix Doubront | Carlos Monasterios | Felix Doubront | Carlos Monasterios | Daniel Bard | 383 | 321 | 62 |
| 2010-06-19 | vs LAN | 70 | W 5-4 | 41-29 | 1 | 37,454 | Tim Wakefield | Vicente Padilla | Jonathan Papelbon | Ronald Belisario | | 388 | 325 | 63 |
| 2010-06-20 | vs LAN | 71 | W 2-0 | 42-29 | 1 | 37,430 | Clay Buchholz | Hiroki Kuroda | Clay Buchholz | Hiroki Kuroda | Jonathan Papelbon | 390 | 325 | 65 |
| 2010-06-22 | @ COL | 72 | L 1-2 | 42-30 | 1 | 48,112 | Jon Lester | Jhoulis Chacin | Jhoulis Chacin | Jon Lester | Matt Belisle | 391 | 327 | 64 |
| 2010-06-23 | @ COL | 73 | L 6-8 | 42-31 | 1 | 48,243 | John Lackey | Ubaldo Jimenez | Manuel Corpas | Jonathan Papelbon | | 397 | 335 | 62 |
| 2010-06-24 | @ COL | 74 | W 13-11 | 43-31 | 1 | 48,582 | Daisuke Matsuzaka | Jason Hammel | Jonathan Papelbon | Huston Street | | 410 | 346 | 64 |
| 2010-06-25 | @ SFN | 75 | L 4-5 | 43-32 | 2 | 41,182 | Tim Wakefield | Jonathan Sanchez | Jonathan Sanchez | Tim Wakefield | Brian Wilson | 414 | 351 | 63 |
| 2010-06-26 | @ SFN | 76 | W 4-2 | 44-32 | 1 | 42,178 | Clay Buchholz | Madison Bumgarner | Scott Atchison | Madison Bumgarner | Jonathan Papelbon | 418 | 353 | 65 |
| 2010-06-27 | @ SFN | 77 | W 5-1 | 45-32 | 1 | 41,528 | Jon Lester | Tim Lincecum | Jon Lester | Tim Lincecum | | 423 | 354 | 69 |
| 2010-06-29 | vs TBA | 78 | W 8-5 | 46-32 | 1 | 38,013 | John Lackey | James Shields | John Lackey | James Shields | Jonathan Papelbon | 431 | 359 | 72 |
| 2010-06-30 | vs TBA | 79 | L 4-9 | 46-33 | 1 | 38,055 | Daisuke Matsuzaka | Matt Garza | Matt Garza | Daisuke Matsuzaka | | 435 | 368 | 67 |
| 2010-07-02 | vs BAL | 80 | W 3-2 | 47-33 | 1 | 38,067 | Tim Wakefield | Brad Bergesen | Tim Wakefield | Brad Bergesen | Jonathan Papelbon | 438 | 370 | 68 |
| 2010-07-03 | vs BAL | 81 | W 9-3 | 48-33 | 1 | 38,106 | Jon Lester | Jeremy Guthrie | Jon Lester | Jeremy Guthrie | | 447 | 373 | 74 |
| 2010-07-04 | vs BAL | 82 | L 1-6 | 48-34 | 1 | 37,742 | John Lackey | Brian Matusz | Brian Matusz | John Lackey | | 448 | 379 | 69 |
| 2010-07-05 | @ TBA | 83 | L 5-6 | 48-35 | 1 | 28,528 | Daisuke Matsuzaka | Matt Garza | Randy Choate | Ramon Ramirez | Rafael Soriano | 453 | 385 | 68 |
| 2010-07-06 | @ TBA | 84 | L 2-3 | 48-36 | 1 | 19,902 | Felix Doubront | Jeff Niemann | Jeff Niemann | Felix Doubront | Rafael Soriano | 455 | 388 | 67 |
| 2010-07-07 | @ TBA | 85 | L 4-6 | 48-37 | 3 | 24,356 | Tim Wakefield | David Price | David Price | Tim Wakefield | Matt Garza | 459 | 394 | 65 |
| 2010-07-09 | @ TOR | 86 | W 14-3 | 48-38 | 3 | 27,567 | Jon Lester | Ricky Romero | Jon Lester | Ricky Romero | | 473 | 397 | 76 |
| 2010-07-10 | @ TOR | 87 | L 5-9 | 48-39 | 3 | 35,037 | John Lackey | Brandon Morrow | Shawn Camp | John Lackey | Kevin Gregg | 478 | 406 | 72 |
| 2010-07-11 | @ TOR | 88 | W 3-2 | 49-39 | 3 | 26,062 | Daisuke Matsuzaka | Jesse Litsch | Daisuke Matsuzaka | Jesse Litsch | Jonathan Papelbon | 481 | 408 | 73 |
| 2010-07-15 | vs TEX | 89 | L 2-7 | 49-40 | 3 | 38,062 | Tim Wakefield | Tommy Hunter | Tommy Hunter | Tim Wakefield | | 483 | 415 | 68 |
| 2010-07-16 | vs TEX | 90 | L 4-8 | 49-41 | 3 | 37,669 | Felix Doubront | Colby Lewis | Colby Lewis | Felix Doubront | | 487 | 423 | 64 |
| 2010-07-17 | vs TEX | 91 | W 3-2 | 50-41 | 3 | 37,744 | John Lackey | Cliff Lee | Manny Delcarmen | Alexi Ogando | | 490 | 425 | 65 |
| 2010-07-18 | vs TEX | 92 | L 2-4 | 50-42 | 3 | 37,431 | Jon Lester | C.J. Wilson | C.J. Wilson | Jon Lester | Neftali Feliz | 492 | 429 | 63 |
| 2010-07-19 | @ OAK | 93 | W 2-1 | 51-42 | 3 | 19,341 | Daisuke Matsuzaka | Ben Sheets | Daisuke Matsuzaka | Ben Sheets | Jonathan Papelbon | 494 | 430 | 64 |
| 2010-07-20 | @ OAK | 94 | L 4-5 | 51-43 | 3 | 20,271 | Tim Wakefield | Dallas Braden | Andrew Bailey | Ramon Ramirez | | 498 | 435 | 63 |
| 2010-07-21 | @ OAK | 95 | L 4-6 | 51-44 | 3 | 30,456 | Clay Buchholz | Gio Gonzalez | Gio Gonzalez | Clay Buchholz | Michael Wuertz | 502 | 441 | 61 |
| 2010-07-22 | @ SEA | 96 | W 8-6 | 52-44 | 3 | 28,074 | John Lackey | Ryan Rowland-Smith | Hideki Okajima | Garrett Olson | Ramon Ramirez | 510 | 447 | 63 |
| 2010-07-23 | @ SEA | 97 | W 2-1 | 53-44 | 3 | 34,932 | Josh Beckett | Jason Vargas | Scott Atchison | Jason Vargas | Jonathan Papelbon | 512 | 448 | 64 |
| 2010-07-24 | @ SEA | 98 | L 1-5 | 53-45 | 3 | 43,694 | Jon Lester | David Pauley | Chris Seddon | Jon Lester | Garrett Olson | 513 | 453 | 60 |
| 2010-07-25 | @ SEA | 99 | L 2-4 | 53-46 | 3 | 40,001 | Daisuke Matsuzaka | Doug Fister | Brandon League | Hideki Okajima | David Aardsma | 515 | 457 | 58 |
| 2010-07-26 | @ ANA | 100 | W 6-3 | 54-46 | 3 | 40,364 | Clay Buchholz | Dan Haren | Clay Buchholz | Dan Haren | Jonathan Papelbon | 521 | 460 | 61 |
| 2010-07-27 | @ ANA | 101 | W 4-2 | 55-46 | 3 | 40,120 | John Lackey | Jered Weaver | John Lackey | Jered Weaver | Jonathan Papelbon | 525 | 462 | 63 |
| 2010-07-28 | @ ANA | 102 | W 7-3 | 56-46 | 3 | 44,052 | Josh Beckett | Scot Shields | Josh Beckett | Fernando Rodney | | 532 | 465 | 67 |
| 2010-07-30 | vs DET | 103 | L 5-6 | 56-47 | 3 | 37,832 | Jon Lester | Armando Galarraga | Robbie Weinhart | Jon Lester | | 537 | 471 | 66 |
| 2010-07-31 | vs DET | 104 | W 5-4 | 57-47 | 3 | 37,498 | Daisuke Matsuzaka | Max Scherzer | Hideki Okajima | Phil Coke | | 542 | 475 | 67 |
| 2010-08-01 | vs DET | 105 | W 4-3 | 58-47 | 3 | 37,479 | Clay Buchholz | Justin Verlander | Jonathan Papelbon | Brad Thomas | | 546 | 478 | 68 |
| 2010-08-02 | vs CLE | 106 | L 5-6 | 58-48 | 3 | 37,931 | John Lackey | Fausto Carmona | Fausto Carmona | John Lackey | Chris Perez | 551 | 484 | 67 |
| 2010-08-03 | vs CLE | 107 | W 3-1 | 59-48 | 3 | 37,714 | Josh Beckett | David Huff | Josh Beckett | David Huff | Jonathan Papelbon | 554 | 485 | 69 |
| 2010-08-04 | vs CLE | 108 | L 1-9 | 59-49 | 3 | 37,902 | Jon Lester | Justin Masterson | Justin Masterson | Jon Lester | | 555 | 494 | 61 |
| 2010-08-05 | vs CLE | 109 | W 6-2 | 60-49 | 3 | 38,102 | Daisuke Matsuzaka | Josh Tomlin | Daisuke Matsuzaka | Josh Tomlin | Jonathan Papelbon | 561 | 496 | 65 |
| 2010-08-06 | @ NYA | 110 | W 6-3 | 61-49 | 3 | 49,555 | Clay Buchholz | Javier Vazquez | Clay Buchholz | Javier Vazquez | Jonathan Papelbon | 567 | 499 | 68 |
| 2010-08-07 | @ NYA | 111 | L 2-5 | 61-50 | 3 | 49,716 | John Lackey | CC Sabathia | CC Sabathia | John Lackey | Mariano Rivera | 569 | 504 | 65 |
| 2010-08-08 | @ NYA | 112 | L 2-7 | 61-51 | 3 | 49,096 | Josh Beckett | Dustin Moseley | Dustin Moseley | Josh Beckett | | 571 | 511 | 60 |
| 2010-08-09 | @ NYA | 113 | W 2-1 | 62-51 | 3 | 49,476 | Jon Lester | Phil Hughes | Jon Lester | Phil Hughes | Jonathan Papelbon | 573 | 512 | 61 |
| 2010-08-10 | @ TOR | 114 | W 7-5 | 63-51 | 3 | 27,690 | Daisuke Matsuzaka | Ricky Romero | Felix Doubront | Shawn Camp | Jonathan Papelbon | 580 | 517 | 63 |
| 2010-08-11 | @ TOR | 115 | W 10-1 | 64-51 | 3 | 28,308 | Clay Buchholz | Shaun Marcum | Clay Buchholz | Shaun Marcum | | 590 | 518 | 72 |
| 2010-08-12 | @ TOR | 116 | L 5-6 | 64-52 | 3 | 36,271 | John Lackey | Brad Mills | Kevin Gregg | Jonathan Papelbon | | 595 | 524 | 71 |
| 2010-08-13 | @ TEX | 117 | L 9-10 | 65-52 | 3 | 47,195 | Josh Beckett | Tommy Hunter | Darren O'Day | Tim Wakefield | | 604 | 534 | 70 |
| 2010-08-14 | @ TEX | 118 | W 3-1 | 66-52 | 3 | 48,030 | Jon Lester | Colby Lewis | Jon Lester | Colby Lewis | Felix Doubront | 607 | 535 | 72 |
| 2010-08-15 | @ TEX | 119 | L 3-7 | 66-53 | 3 | 30,252 | Daisuke Matsuzaka | C.J. Wilson | C.J. Wilson | Daisuke Matsuzaka | | 610 | 542 | 68 |
| 2010-08-17 | vs ANA | 120 | W 6-0 | 67-53 | 2 | 38,304 | Clay Buchholz | Jered Weaver | Clay Buchholz | Jered Weaver | | 616 | 542 | 74 |
| 2010-08-18 | vs ANA | 121 | W 7-5 | 68-53 | 2 | 37,779 | John Lackey | Scott Kazmir | John Lackey | Kevin Jepsen | Jonathan Papelbon | 623 | 547 | 76 |
| 2010-08-19 | vs ANA | 122 | L 2-7 | 68-54 | 2 | 37,641 | Josh Beckett | Ervin Santana | Ervin Santana | Josh Beckett | | 625 | 554 | 71 |
| 2010-08-20 | vs TOR | 123 | L 2-16 | 69-54 | 2 | 37,726 | Jon Lester | Brett Cecil | Brett Cecil | Jon Lester | | 627 | 570 | 57 |
| 2010-08-21 | vs TOR | 124 | W 5-4 | 70-54 | 2 | 37,614 | Daisuke Matsuzaka | Ricky Romero | Jonathan Papelbon | Casey Janssen | | 632 | 574 | 58 |
| 2010-08-22 | vs TOR | 125 | W 5-0 | 71-54 | 2 | 37,506 | Clay Buchholz | Shaun Marcum | Clay Buchholz | Shaun Marcum | Felix Doubront | 637 | 574 | 63 |
| 2010-08-23 | vs SEA | 126 | W 6-3 | 72-54 | 2 | 37,133 | John Lackey | Doug Fister | John Lackey | Doug Fister | Jonathan Papelbon | 643 | 577 | 66 |
| 2010-08-25 | vs SEA | 127 | W 5-3 | 73-55 | 3 | 37,183 | Josh Beckett | David Pauley | Josh Beckett | David Pauley | Jonathan Papelbon | 648 | 580 | 68 |
| 2010-08-25 | vs SEA | 128 | L 2-4 | 73-55 | 3 | 37,451 | Tim Wakefield | Felix Hernandez | Felix Hernandez | Tim Wakefield | Brandon League | 650 | 584 | 66 |
| 2010-08-27 | @ TBA | 129 | W 3-1 | 74-55 | 2 | 29,461 | Jon Lester | David Price | Jon Lester | David Price | Jonathan Papelbon | 653 | 585 | 68 |
| 2010-08-28 | @ TBA | 130 | L 2-3 | 74-56 | 2 | 36,973 | Clay Buchholz | Matt Garza | Randy Choate | Scott Atchison | | 655 | 588 | 67 |
| 2010-08-29 | @ TBA | 131 | L 3-5 | 74-57 | 2 | 23,438 | John Lackey | James Shields | James Shields | John Lackey | Rafael Soriano | 658 | 593 | 65 |
| 2010-08-31 | @ BAL | 132 | L 2-5 | 74-58 | 2 | 18,247 | Josh Beckett | Brian Matusz | Brian Matusz | Josh Beckett | Koji Uehara | 660 | 598 | 62 |
| 2010-09-01 | @ BAL | 133 | W 9-6 | 75-58 | 2 | 16,210 | Jon Lester | Jake Arrieta | Jon Lester | Mark Hendrickson | Jonathan Papelbon | 669 | 604 | 65 |
| 2010-09-02 | @ BAL | 134 | W 6-4 | 76-58 | 2 | 26,954 | Daisuke Matsuzaka | Brad Bergesen | Daisuke Matsuzaka | Brad Bergesen | Jonathan Papelbon | 675 | 608 | 67 |
| 2010-09-04 | vs CHA | 135 | L 1-3 | 76-60 | 3 | 37,411 | Clay Buchholz | John Danks | John Danks | Clay Buchholz | Bobby Jenks | 676 | 611 | 65 |
| 2010-09-04 | vs CHA | 136 | L 1-3 | 76-60 | 3 | 37,858 | John Lackey | Gavin Floyd | Gavin Floyd | John Lackey | Bobby Jenks | 677 | 614 | 63 |
| 2010-09-05 | vs CHA | 137 | L 5-7 | 76-61 | 2 | 37,570 | Josh Beckett | Mark Buehrle | Scott Linebrink | Jonathan Papelbon | Matt Thornton | 682 | 621 | 61 |
| 2010-09-06 | vs TBA | 138 | W 12-5 | 76-62 | 2 | 37,546 | Jon Lester | Jeff Niemann | Jon Lester | Jeff Niemann | | 694 | 626 | 68 |
| 2010-09-07 | vs TBA | 139 | L 5-14 | 77-62 | 2 | 37,290 | Daisuke Matsuzaka | David Price | David Price | Daisuke Matsuzaka | | 699 | 640 | 59 |
| 2010-09-08 | vs TBA | 140 | W 11-5 | 77-63 | 2 | 37,757 | Tim Wakefield | Matt Garza | Tim Wakefield | Matt Garza | | 710 | 645 | 65 |
| 2010-09-10 | @ OAK | 141 | L 0-5 | 77-64 | 2 | 19,139 | Clay Buchholz | Trevor Cahill | Trevor Cahill | Clay Buchholz | | 710 | 650 | 60 |
| 2010-09-11 | @ OAK | 142 | L 3-4 | 77-65 | 2 | 22,932 | John Lackey | Brett Anderson | Brett Anderson | John Lackey | Andrew Bailey | 713 | 654 | 59 |
| 2010-09-12 | @ OAK | 143 | W 5-3 | 78-65 | 2 | 19,806 | Josh Beckett | Dallas Braden | Josh Beckett | Dallas Braden | Jonathan Papelbon | 718 | 657 | 61 |
| 2010-09-13 | @ SEA | 144 | W 5-1 | 79-65 | 2 | 19,063 | Jon Lester | Doug Fister | Jon Lester | Doug Fister | | 723 | 658 | 65 |
| 2010-09-14 | @ SEA | 145 | W 9-6 | 80-65 | 2 | 18,381 | Daisuke Matsuzaka | Lucas French | Rich Hill | Brandon League | | 732 | 664 | 68 |
| 2010-09-15 | @ SEA | 146 | W 5-1 | 81-65 | 2 | 21,936 | Clay Buchholz | David Pauley | Clay Buchholz | David Pauley | | 737 | 665 | 72 |
| 2010-09-17 | vs TOR | 147 | L 9-11 | 82-65 | 2 | 37,679 | John Lackey | Brett Cecil | Brett Cecil | John Lackey | Kevin Gregg | 746 | 676 | 70 |
| 2010-09-18 | vs TOR | 148 | L 3-4 | 82-66 | 2 | 37,863 | Josh Beckett | Ricky Romero | Ricky Romero | Josh Beckett | Kevin Gregg | 749 | 680 | 69 |
| 2010-09-19 | vs TOR | 149 | W 6-0 | 83-66 | 2 | 37,234 | Jon Lester | Shaun Marcum | Jon Lester | Shaun Marcum | | 755 | 680 | 75 |
| 2010-09-20 | vs BAL | 150 | L 2-4 | 83-67 | 2 | 37,560 | Daisuke Matsuzaka | Brian Matusz | David Hernandez | Daisuke Matsuzaka | Koji Uehara | 757 | 684 | 73 |
| 2010-09-21 | vs BAL | 151 | L 1-9 | 83-68 | 2 | 37,464 | Clay Buchholz | Brad Bergesen | Brad Bergesen | Scott Atchison | | 758 | 693 | 65 |
| 2010-09-22 | vs BAL | 152 | W 6-1 | 84-68 | 2 | 37,729 | John Lackey | Kevin Millwood | John Lackey | Kevin Millwood | | 764 | 694 | 70 |
| 2010-09-24 | @ NYA | 153 | W 10-8 | 84-69 | 2 | 49,457 | Josh Beckett | Andy Pettitte | Josh Beckett | Andy Pettitte | Jonathan Papelbon | 774 | 702 | 72 |
| 2010-09-25 | @ NYA | 154 | W 7-3 | 85-69 | 2 | 49,558 | Jon Lester | Ivan Nova | Jon Lester | Ivan Nova | | 781 | 705 | 76 |
| 2010-09-26 | @ NYA | 155 | L 3-4 | 85-70 | 2 | 49,199 | Daisuke Matsuzaka | Phil Hughes | Boone Logan | Hideki Okajima | | 784 | 709 | 75 |
| 2010-09-27 | @ CHA | 156 | W 6-1 | 86-70 | 2 | 19,750 | Clay Buchholz | Mark Buehrle | Clay Buchholz | Mark Buehrle | | 790 | 710 | 80 |
| 2010-09-28 | @ CHA | 157 | L 4-5 | 86-71 | 2 | 16,982 | John Lackey | Edwin Jackson | Chris Sale | Michael Bowden | | 794 | 715 | 79 |
| 2010-09-29 | @ CHA | 158 | L 2-5 | 86-72 | 2 | 32,084 | Josh Beckett | Freddy Garcia | Freddy Garcia | Josh Beckett | Matt Thornton | 796 | 720 | 76 |
| 2010-09-30 | @ CHA | 159 | L 2-8 | 86-73 | 2 | 30,854 | Jon Lester | John Danks | John Danks | Jon Lester | | 798 | 728 | 70 |
| 2010-10-02 | vs NYA | 160 | L 5-6 | 86-74 | 3 | 37,467 | Tim Wakefield | Andy Pettitte | Phil Hughes | Jonathan Papelbon | Mariano Rivera | 803 | 734 | 69 |
| 2010-10-02 | vs NYA | 161 | W 7-6 | 86-74 | 3 | 37,589 | Daisuke Matsuzaka | A.J. Burnett | Robert Manuel | Ivan Nova | | 810 | 740 | 70 |
| 2010-10-03 | vs NYA | 162 | W 8-4 | 88-74 | 2 | 37,453 | John Lackey | Dustin Moseley | John Lackey | Dustin Moseley | | 818 | 744 | 74 |