| 1991-04-08 | @ TOR | 1 | W 6-2 | 1-0 | 1 | 50,114 | Roger Clemens | Dave Stieb | Roger Clemens | Dave Stieb | | 6 | 2 | 4 |
| 1991-04-09 | @ TOR | 2 | L 3-4 | 1-1 | 3 | 42,211 | Greg Harris | Jimmy Key | Jimmy Key | Greg Harris | Tom Henke | 9 | 6 | 3 |
| 1991-04-10 | @ TOR | 3 | L 3-5 | 1-2 | 5 | 41,164 | Matt Young | Todd Stottlemyre | Mike Timlin | Jeff Gray | Tom Henke | 12 | 11 | 1 |
| 1991-04-11 | vs CLE | 4 | L 4-6 | 1-3 | 6 | 34,134 | Danny Darwin | Eric King | Eric King | Danny Darwin | Doug Jones | 16 | 17 | -1 |
| 1991-04-13 | vs CLE | 5 | W 4-0 | 2-3 | 4 | 33,212 | Roger Clemens | Greg Swindell | Roger Clemens | Greg Swindell | | 20 | 17 | 3 |
| 1991-04-14 | vs CLE | 6 | L 0-6 | 2-4 | 6 | 33,348 | Greg Harris | Tom Candiotti | Tom Candiotti | Greg Harris | | 20 | 23 | -3 |
| 1991-04-15 | vs CLE | 7 | L 0-1 | 2-5 | 6 | 33,205 | Matt Young | Charles Nagy | Steve Olin | Dennis Lamp | Doug Jones | 20 | 24 | -4 |
| 1991-04-16 | vs KCA | 8 | W 5-2 | 3-5 | 6 | 25,815 | Danny Darwin | Kevin Appier | Danny Darwin | Kevin Appier | Jeff Reardon | 25 | 26 | -1 |
| 1991-04-17 | vs KCA | 9 | W 6-2 | 4-5 | 5 | 24,651 | Tom Bolton | Storm Davis | Tom Bolton | Storm Davis | Jeff Gray | 31 | 28 | 3 |
| 1991-04-18 | vs KCA | 10 | W 1-0 | 5-5 | 4 | 29,658 | Roger Clemens | Bret Saberhagen | Roger Clemens | Bret Saberhagen | Jeff Reardon | 32 | 28 | 4 |
| 1991-04-20 | @ CLE | 11 | W 2-1 | 6-5 | 3 | 9,153 | Greg Harris | Tom Candiotti | Greg Harris | Tom Candiotti | Jeff Reardon | 34 | 29 | 5 |
| 1991-04-22 | vs TOR | 12 | W 6-4 | 7-5 | 1 | 25,841 | Danny Darwin | David Wells | Dennis Lamp | David Wells | Jeff Reardon | 40 | 33 | 7 |
| 1991-04-23 | vs TOR | 13 | W 3-0 | 8-5 | 1 | 29,904 | Roger Clemens | Denis Boucher | Roger Clemens | Denis Boucher | Jeff Reardon | 43 | 33 | 10 |
| 1991-04-24 | vs TOR | 14 | L 1-6 | 8-6 | 1 | 28,841 | Matt Young | Dave Stieb | Dave Stieb | Matt Young | | 44 | 39 | 5 |
| 1991-04-26 | @ KCA | 15 | L 3-5 | 8-7 | 2 | 22,559 | Greg Harris | Mike Boddicker | Mike Boddicker | Tony Fossas | Jeff Montgomery | 47 | 44 | 3 |
| 1991-04-27 | @ KCA | 16 | W 6-4 | 9-7 | 2 | 29,858 | Tom Bolton | Kevin Appier | Tom Bolton | Kevin Appier | Jeff Reardon | 53 | 48 | 5 |
| 1991-04-28 | @ KCA | 17 | W 2-1 | 10-7 | 2 | 21,426 | Dana Kiecker | Storm Davis | Dana Kiecker | Tom Gordon | Jeff Reardon | 55 | 49 | 6 |
| 1991-04-30 | @ MIN | 18 | W 7-5 | 11-7 | 1 | 15,343 | Matt Young | Allan Anderson | Jeff Gray | Steve Bedrosian | Jeff Reardon | 62 | 54 | 8 |
| 1991-05-01 | @ MIN | 19 | L 0-1 | 11-8 | 1 | 14,449 | Greg Harris | Scott Erickson | Scott Erickson | Jeff Gray | | 62 | 55 | 7 |
| 1991-05-03 | @ CHA | 20 | W 7-2 | 12-8 | 1 | 30,267 | Roger Clemens | Jack McDowell | Roger Clemens | Jack McDowell | | 69 | 57 | 12 |
| 1991-05-04 | @ CHA | 21 | W 4-0 | 13-8 | 1 | 37,121 | Tom Bolton | Melido Perez | Tom Bolton | Melido Perez | | 73 | 57 | 16 |
| 1991-05-05 | @ CHA | 22 | W 9-1 | 14-8 | 1 | 34,477 | Matt Young | Alex Fernandez | Matt Young | Alex Fernandez | | 82 | 58 | 24 |
| 1991-05-07 | vs MIN | 23 | L 3-9 | 14-9 | 1 | 23,815 | Greg Harris | Scott Erickson | Scott Erickson | Greg Harris | | 85 | 67 | 18 |
| 1991-05-08 | vs MIN | 24 | W 8-3 | 15-9 | 1 | 25,134 | Roger Clemens | Jack Morris | Roger Clemens | Jack Morris | | 93 | 70 | 23 |
| 1991-05-09 | vs TEX | 25 | W 8-4 | 16-9 | 1 | 26,756 | Tom Bolton | Scott Chiamparino | Dennis Lamp | Mike Jeffcoat | | 101 | 74 | 27 |
| 1991-05-10 | vs TEX | 26 | W 5-3 | 17-9 | 1 | 33,695 | Matt Young | Bobby Witt | Matt Young | Bobby Witt | Jeff Reardon | 106 | 77 | 29 |
| 1991-05-11 | vs TEX | 27 | W 5-4 | 18-9 | 1 | 33,798 | Dana Kiecker | Kevin Brown | Dana Kiecker | Kevin Brown | Jeff Reardon | 111 | 81 | 30 |
| 1991-05-12 | vs TEX | 28 | L 5-12 | 18-10 | 1 | 33,196 | Greg Harris | Kenny Rogers | Kenny Rogers | Greg Harris | | 116 | 93 | 23 |
| 1991-05-13 | vs CHA | 29 | L 3-4 | 18-11 | 1 | 31,032 | Roger Clemens | Jack McDowell | Bobby Thigpen | Jeff Gray | | 119 | 97 | 22 |
| 1991-05-14 | vs CHA | 30 | W 4-1 | 19-11 | 1 | 28,927 | Tom Bolton | Melido Perez | Tom Bolton | Melido Perez | Jeff Reardon | 123 | 98 | 25 |
| 1991-05-15 | vs CHA | 31 | W 9-6 | 20-11 | 1 | 31,712 | Matt Young | Alex Fernandez | Joe Hesketh | Donn Pall | Jeff Reardon | 132 | 104 | 28 |
| 1991-05-17 | @ TEX | 32 | L 4-6 | 20-12 | 1 | 32,208 | Greg Harris | Kevin Brown | Kevin Brown | Greg Harris | Jeff Russell | 136 | 110 | 26 |
| 1991-05-18 | @ TEX | 33 | L 5-13 | 20-13 | 1 | 42,696 | Roger Clemens | Kenny Rogers | Kenny Rogers | Roger Clemens | Jim Poole | 141 | 123 | 18 |
| 1991-05-19 | @ TEX | 34 | L 4-12 | 20-14 | 1 | 39,895 | Tom Bolton | John Barfield | Gerald Alexander | Tom Bolton | | 145 | 135 | 10 |
| 1991-05-20 | vs MIL | 35 | W 3-0 | 21-14 | 1 | 28,983 | Matt Young | Chris Bosio | Matt Young | Chris Bosio | Jeff Reardon | 148 | 135 | 13 |
| 1991-05-21 | vs MIL | 36 | W 10-6 | 22-14 | 1 | 28,646 | Dana Kiecker | Bill Wegman | Joe Hesketh | Jim Hunter | | 158 | 141 | 17 |
| 1991-05-22 | vs MIL | 37 | W 4-0 | 23-14 | 1 | 33,182 | Danny Darwin | Kevin Brown | Danny Darwin | Kevin Brown | Greg Harris | 162 | 141 | 21 |
| 1991-05-23 | @ DET | 38 | L 3-5 | 23-15 | 1 | 14,744 | Roger Clemens | Frank Tanana | Mike Henneman | Roger Clemens | Paul Gibson | 165 | 146 | 19 |
| 1991-05-24 | @ DET | 39 | W 10-9 | 24-15 | 1 | 16,546 | Tom Bolton | Dan Petry | Tom Bolton | Dan Petry | Jeff Reardon | 175 | 155 | 20 |
| 1991-05-25 | @ DET | 40 | L 2-3 | 24-16 | 1 | 19,179 | Matt Young | Walt Terrell | Walt Terrell | Matt Young | Mike Henneman | 177 | 158 | 19 |
| 1991-05-26 | @ DET | 41 | L 4-9 | 24-17 | 1 | 24,821 | Dana Kiecker | John Cerutti | Mark Leiter | Dana Kiecker | Paul Gibson | 181 | 167 | 14 |
| 1991-05-27 | @ NYA | 42 | L 5-6 | 24-18 | 1 | 32,369 | Danny Darwin | Dave Eiland | Lee Guetterman | Jeff Reardon | | 186 | 173 | 13 |
| 1991-05-28 | @ NYA | 43 | W 6-2 | 25-18 | 1 | 32,943 | Roger Clemens | Tim Leary | Roger Clemens | Tim Leary | | 192 | 175 | 17 |
| 1991-05-29 | @ NYA | 44 | L 0-7 | 25-19 | 1 | 25,242 | Tom Bolton | Scott Sanderson | Scott Sanderson | Tom Bolton | | 192 | 182 | 10 |
| 1991-05-30 | vs BAL | 45 | L 3-9 | 25-20 | 1 | 33,795 | Matt Young | Jeff Ballard | Jeff Ballard | Matt Young | Mike Flanagan | 195 | 191 | 4 |
| 1991-05-31 | vs BAL | 46 | W 7-2 | 26-20 | 1 | 33,744 | Mike Gardiner | Jose Mesa | Mike Gardiner | Jose Mesa | | 202 | 193 | 9 |
| 1991-06-01 | vs BAL | 47 | L 1-3 | 26-21 | 1 | 33,648 | Danny Darwin | Bob Milacki | Kevin Hickey | Danny Darwin | Gregg Olson | 203 | 196 | 7 |
| 1991-06-02 | vs BAL | 48 | L 1-5 | 26-22 | 1 | 34,305 | Roger Clemens | Roy Smith | Roy Smith | Roger Clemens | Mark Williamson | 204 | 201 | 3 |
| 1991-06-04 | @ CAL | 49 | L 0-3 | 26-23 | 2 | 26,087 | Tom Bolton | Chuck Finley | Chuck Finley | Tom Bolton | | 204 | 204 | 0 |
| 1991-06-05 | @ CAL | 50 | L 2-7 | 26-24 | 2 | 24,089 | Mike Gardiner | Kirk McCaskill | Kirk McCaskill | Mike Gardiner | | 206 | 211 | -5 |
| 1991-06-06 | @ CAL | 51 | L 2-3 | 26-25 | 2 | 27,227 | Danny Darwin | Mark Langston | Mark Langston | Danny Darwin | Bryan Harvey | 208 | 214 | -6 |
| 1991-06-07 | @ OAK | 52 | W 3-1 | 27-25 | 2 | 37,365 | Greg Harris | Mike Moore | Greg Harris | Mike Moore | Jeff Reardon | 211 | 215 | -4 |
| 1991-06-08 | @ OAK | 53 | W 8-1 | 28-25 | 2 | 44,347 | Roger Clemens | Joe Slusarski | Roger Clemens | Joe Slusarski | | 219 | 216 | 3 |
| 1991-06-09 | @ OAK | 54 | L 0-8 | 28-26 | 2 | 44,595 | Tom Bolton | Bob Welch | Bob Welch | Tom Bolton | | 219 | 224 | -5 |
| 1991-06-10 | @ SEA | 55 | W 6-2 | 29-26 | 2 | 32,082 | Mike Gardiner | Randy Johnson | Mike Gardiner | Randy Johnson | | 225 | 226 | -1 |
| 1991-06-11 | @ SEA | 56 | W 8-5 | 30-26 | 1 | 20,833 | Danny Darwin | Scott Bankhead | Danny Darwin | Scott Bankhead | Jeff Reardon | 233 | 231 | 2 |
| 1991-06-12 | @ SEA | 57 | L 3-5 | 30-27 | 2 | 19,641 | Greg Harris | Bill Krueger | Bill Krueger | Greg Harris | Michael Jackson | 236 | 236 | 0 |
| 1991-06-14 | vs CAL | 58 | W 9-4 | 31-27 | 2 | 34,299 | Roger Clemens | Jim Abbott | Roger Clemens | Jeff Robinson | | 245 | 240 | 5 |
| 1991-06-15 | vs CAL | 59 | W 13-3 | 32-27 | 2 | 32,591 | Mike Gardiner | Chuck Finley | Mike Gardiner | Chuck Finley | | 258 | 243 | 15 |
| 1991-06-16 | vs CAL | 60 | W 2-0 | 33-27 | 1 | 32,433 | Tom Bolton | Kirk McCaskill | Tom Bolton | Kirk McCaskill | Jeff Reardon | 260 | 243 | 17 |
| 1991-06-17 | vs CAL | 61 | L 2-4 | 33-28 | 1 | 32,786 | Greg Harris | Mark Langston | Mark Langston | Greg Harris | Bryan Harvey | 262 | 247 | 15 |
| 1991-06-18 | vs SEA | 62 | L 1-2 | 33-29 | 1 | 33,948 | Danny Darwin | Bill Krueger | Bill Krueger | Jeff Reardon | Michael Jackson | 263 | 249 | 14 |
| 1991-06-19 | vs SEA | 63 | L 3-4 | 33-30 | 1 | 33,251 | Roger Clemens | Rich DeLucia | Russ Swan | Roger Clemens | Michael Jackson | 266 | 253 | 13 |
| 1991-06-20 | vs OAK | 64 | W 8-7 | 34-30 | 1 | 33,769 | Mike Gardiner | Dave Stewart | Jeff Gray | Steve Chitren | Jeff Reardon | 274 | 260 | 14 |
| 1991-06-21 | vs OAK | 65 | W 3-2 | 35-30 | 1 | 33,951 | Tom Bolton | Mike Moore | Tom Bolton | Mike Moore | Jeff Reardon | 277 | 262 | 15 |
| 1991-06-22 | vs OAK | 66 | W 9-5 | 36-30 | 1 | 34,120 | Greg Harris | Joe Slusarski | Greg Harris | Joe Slusarski | | 286 | 267 | 19 |
| 1991-06-23 | vs OAK | 67 | L 2-4 | 36-31 | 2 | 34,147 | Danny Darwin | Bob Welch | Bob Welch | Danny Darwin | Dennis Eckersley | 288 | 271 | 17 |
| 1991-06-25 | vs NYA | 68 | L 4-6 | 36-32 | 2 | 34,753 | Roger Clemens | Tim Leary | Tim Leary | Roger Clemens | Steve Farr | 292 | 277 | 15 |
| 1991-06-26 | vs NYA | 69 | L 1-5 | 36-33 | 2 | 34,514 | Mike Gardiner | Scott Sanderson | Scott Sanderson | Mike Gardiner | Steve Howe | 293 | 282 | 11 |
| 1991-06-27 | vs NYA | 70 | L 0-8 | 36-34 | 2 | 34,529 | Tom Bolton | Wade Taylor | Wade Taylor | Tom Bolton | | 293 | 290 | 3 |
| 1991-06-28 | @ BAL | 71 | W 9-3 | 37-34 | 2 | 48,327 | Greg Harris | Jose Mesa | Greg Harris | Jose Mesa | | 302 | 293 | 9 |
| 1991-06-29 | @ BAL | 72 | L 3-7 | 37-35 | 2 | 44,023 | Danny Darwin | Roy Smith | Roy Smith | Danny Darwin | | 305 | 300 | 5 |
| 1991-06-30 | @ BAL | 73 | L 4-6 | 37-36 | 2 | 47,274 | Joe Hesketh | Jeff Robinson | Mark Williamson | Joe Hesketh | Gregg Olson | 309 | 306 | 3 |
| 1991-07-01 | @ MIL | 74 | W 6-0 | 38-36 | 2 | 14,955 | Roger Clemens | Jaime Navarro | Roger Clemens | Jaime Navarro | | 315 | 306 | 9 |
| 1991-07-02 | @ MIL | 75 | W 14-4 | 39-36 | 2 | 16,019 | Tom Bolton | Mark Knudson | Dennis Lamp | Mark Knudson | | 329 | 310 | 19 |
| 1991-07-03 | @ MIL | 76 | W 5-3 | 40-36 | 2 | 23,935 | Greg Harris | Don August | Greg Harris | Don August | Jeff Reardon | 334 | 313 | 21 |
| 1991-07-04 | vs DET | 77 | L 1-6 | 40-37 | 2 | 33,611 | Danny Darwin | Rusty Meacham | Rusty Meacham | Danny Darwin | | 335 | 319 | 16 |
| 1991-07-05 | vs DET | 78 | W 10-1 | 41-37 | 2 | 33,997 | Kevin Morton | Walt Terrell | Kevin Morton | Walt Terrell | | 345 | 320 | 25 |
| 1991-07-06 | vs DET | 79 | W 7-4 | 42-37 | 2 | 34,440 | Roger Clemens | Dan Gakeler | Roger Clemens | Paul Gibson | Jeff Reardon | 352 | 324 | 28 |
| 1991-07-07 | vs DET | 80 | L 6-7 | 42-38 | 2 | 33,648 | Tom Bolton | Bill Gullickson | Bill Gullickson | Tom Bolton | John Cerutti | 358 | 331 | 27 |
| 1991-07-11 | @ MIN | 81 | L 3-7 | 42-39 | 2 | 31,409 | Greg Harris | Kevin Tapani | Carl Willis | Greg Harris | | 361 | 338 | 23 |
| 1991-07-12 | @ MIN | 82 | L 4-5 | 42-40 | 2 | 37,262 | Roger Clemens | Allan Anderson | Paul Abbott | Roger Clemens | Rick Aguilera | 365 | 343 | 22 |
| 1991-07-13 | @ MIN | 83 | L 1-3 | 42-41 | 4 | 42,803 | Kevin Morton | Jack Morris | Jack Morris | Kevin Morton | Rick Aguilera | 366 | 346 | 20 |
| 1991-07-14 | @ MIN | 84 | W 5-3 | 43-41 | 2 | 38,066 | Joe Hesketh | David West | Joe Hesketh | David West | Jeff Reardon | 371 | 349 | 22 |
| 1991-07-15 | @ CHA | 85 | L 1-7 | 43-42 | 3 | 34,798 | Mike Gardiner | Ramon Garcia | Ramon Garcia | Mike Gardiner | Ken Patterson | 372 | 356 | 16 |
| 1991-07-16 | @ CHA | 86 | W 2-0 | 44-42 | 3 | 37,527 | Greg Harris | Charlie Hough | Greg Harris | Charlie Hough | Jeff Reardon | 374 | 356 | 18 |
| 1991-07-17 | @ CHA | 87 | W 4-2 | 45-42 | 3 | 40,008 | Roger Clemens | Greg Hibbard | Tony Fossas | Bobby Thigpen | | 378 | 358 | 20 |
| 1991-07-18 | vs MIN | 88 | L 3-11 | 45-43 | 3 | 34,630 | Kevin Morton | Jack Morris | Jack Morris | Kevin Morton | | 381 | 369 | 12 |
| 1991-07-19 | vs MIN | 89 | L 2-3 | 45-44 | 3 | 33,758 | Joe Hesketh | David West | Steve Bedrosian | Greg Harris | Rick Aguilera | 383 | 372 | 11 |
| 1991-07-20 | vs MIN | 90 | L 0-5 | 45-45 | 4 | 33,005 | Mike Gardiner | Scott Erickson | Scott Erickson | Mike Gardiner | Mark Guthrie | 383 | 377 | 6 |
| 1991-07-21 | vs MIN | 91 | L 1-14 | 45-46 | 4 | 32,849 | Tom Bolton | Kevin Tapani | Kevin Tapani | Tom Bolton | | 384 | 391 | -7 |
| 1991-07-22 | @ TEX | 92 | L 1-2 | 45-47 | 4 | 36,430 | Roger Clemens | Jose Guzman | Jose Guzman | Roger Clemens | Jeff Russell | 385 | 393 | -8 |
| 1991-07-23 | @ TEX | 93 | L 4-5 | 45-48 | 4 | 40,481 | Greg Harris | Nolan Ryan | Nolan Ryan | Greg Harris | Rich Gossage | 389 | 398 | -9 |
| 1991-07-24 | @ TEX | 94 | W 2-1 | 46-48 | 4 | 39,439 | Joe Hesketh | Oil Can Boyd | Joe Hesketh | Oil Can Boyd | Jeff Reardon | 391 | 399 | -8 |
| 1991-07-27 | vs CHA | 95 | L 8-10 | 46-50 | 4 | 33,461 | Roger Clemens | Greg Hibbard | Melido Perez | Dana Kiecker | Bobby Thigpen | 399 | 409 | -10 |
| 1991-07-27 | vs CHA | 96 | L 4-7 | 46-50 | 4 | 24,673 | Mike Gardiner | Ramon Garcia | Ramon Garcia | Mike Gardiner | Bobby Thigpen | 403 | 416 | -13 |
| 1991-07-28 | vs CHA | 97 | L 2-5 | 46-51 | 4 | 33,166 | Greg Harris | Alex Fernandez | Alex Fernandez | Greg Harris | Bobby Thigpen | 405 | 421 | -16 |
| 1991-07-29 | vs TEX | 98 | L 2-7 | 46-52 | 4 | 33,604 | Joe Hesketh | Jose Guzman | Jose Guzman | Joe Hesketh | Kenny Rogers | 407 | 428 | -21 |
| 1991-07-30 | vs TEX | 99 | W 11-6 | 47-52 | 4 | 33,086 | Kevin Morton | Oil Can Boyd | Kevin Morton | Oil Can Boyd | | 418 | 434 | -16 |
| 1991-07-31 | vs OAK | 100 | W 11-10 | 48-52 | 3 | 34,218 | Dana Kiecker | Dave Stewart | Greg Harris | Steve Chitren | | 429 | 444 | -15 |
| 1991-08-01 | vs OAK | 101 | L 2-4 | 48-53 | 4 | 34,099 | Mike Gardiner | Eric Show | Joe Klink | Dennis Lamp | Dennis Eckersley | 431 | 448 | -17 |
| 1991-08-02 | vs TOR | 102 | W 5-3 | 49-53 | 3 | 34,032 | Roger Clemens | Tom Candiotti | Roger Clemens | Tom Candiotti | | 436 | 451 | -15 |
| 1991-08-03 | vs TOR | 103 | W 4-1 | 50-53 | 3 | 34,015 | Joe Hesketh | David Wells | Joe Hesketh | David Wells | Jeff Reardon | 440 | 452 | -12 |
| 1991-08-04 | vs TOR | 104 | L 1-2 | 50-54 | 3 | 33,809 | Greg Harris | Todd Stottlemyre | Duane Ward | Dennis Lamp | Tom Henke | 441 | 454 | -13 |
| 1991-08-05 | @ KCA | 105 | L 3-5 | 50-55 | 3 | 36,154 | Kevin Morton | Luis Aquino | Jeff Montgomery | Tony Fossas | | 444 | 459 | -15 |
| 1991-08-06 | @ KCA | 106 | L 0-6 | 50-56 | 3 | 26,141 | Mike Gardiner | Mike Boddicker | Mike Boddicker | Mike Gardiner | | 444 | 465 | -21 |
| 1991-08-07 | @ KCA | 107 | L 0-2 | 50-57 | 3 | 32,226 | Roger Clemens | Kevin Appier | Kevin Appier | Roger Clemens | | 444 | 467 | -23 |
| 1991-08-09 | @ TOR | 108 | W 12-7 | 51-57 | 3 | 50,319 | Joe Hesketh | David Wells | Joe Hesketh | David Wells | Jeff Reardon | 456 | 474 | -18 |
| 1991-08-10 | @ TOR | 109 | W 7-1 | 52-57 | 3 | 50,304 | Greg Harris | Todd Stottlemyre | Greg Harris | Todd Stottlemyre | | 463 | 475 | -12 |
| 1991-08-11 | @ TOR | 110 | W 9-6 | 53-57 | 3 | 50,297 | Mike Gardiner | Jimmy Key | Mike Gardiner | Jimmy Key | Jeff Reardon | 472 | 481 | -9 |
| 1991-08-12 | @ TOR | 111 | W 11-8 | 54-57 | 3 | 50,305 | Roger Clemens | Juan Guzman | Dennis Lamp | Duane Ward | Jeff Reardon | 483 | 489 | -6 |
| 1991-08-13 | @ CLE | 112 | L 6-8 | 55-58 | 3 | 0 | Matt Young | Charles Nagy | Shawn Hillegas | Dana Kiecker | Steve Olin | 489 | 497 | -8 |
| 1991-08-13 | @ CLE | 113 | W 7-5 | 55-58 | 3 | 15,506 | Kevin Morton | Mauro Gozzo | Tony Fossas | Rod Nichols | Jeff Reardon | 496 | 502 | -6 |
| 1991-08-14 | @ CLE | 114 | W 2-1 | 56-58 | 3 | 10,636 | Joe Hesketh | Greg Swindell | Joe Hesketh | Greg Swindell | Jeff Reardon | 498 | 503 | -5 |
| 1991-08-15 | @ CLE | 115 | W 6-2 | 57-58 | 3 | 9,160 | Mike Gardiner | Dave Otto | Mike Gardiner | Dave Otto | | 504 | 505 | -1 |
| 1991-08-16 | vs KCA | 116 | W 3-2 | 58-58 | 3 | 34,548 | Roger Clemens | Bret Saberhagen | Tony Fossas | Storm Davis | Jeff Reardon | 507 | 507 | 0 |
| 1991-08-17 | vs KCA | 117 | L 3-4 | 58-59 | 3 | 34,009 | Matt Young | Luis Aquino | Luis Aquino | Jeff Reardon | Jeff Montgomery | 510 | 511 | -1 |
| 1991-08-18 | vs KCA | 118 | W 5-1 | 59-59 | 3 | 34,198 | Kevin Morton | Kevin Appier | Kevin Morton | Kevin Appier | | 515 | 512 | 3 |
| 1991-08-21 | vs CLE | 119 | W 13-5 | 61-59 | 3 | 33,000 | Joe Hesketh | Greg Swindell | Joe Hesketh | Greg Swindell | | 528 | 517 | 11 |
| 1991-08-21 | vs CLE | 120 | W 5-4 | 61-59 | 3 | 34,069 | Roger Clemens | Dave Otto | Greg Harris | Steve Olin | | 533 | 521 | 12 |
| 1991-08-22 | vs CLE | 121 | W 7-6 | 62-59 | 3 | 14,037 | Mike Gardiner | Eric King | Greg Harris | Steve Olin | | 540 | 527 | 13 |
| 1991-08-23 | @ CAL | 122 | L 1-4 | 62-60 | 3 | 29,698 | Matt Young | Jim Abbott | Jim Abbott | Matt Young | Bryan Harvey | 541 | 531 | 10 |
| 1991-08-24 | @ CAL | 123 | L 0-1 | 62-61 | 3 | 31,597 | Kevin Morton | Kirk McCaskill | Kirk McCaskill | Kevin Morton | Bryan Harvey | 541 | 532 | 9 |
| 1991-08-25 | @ CAL | 124 | L 5-9 | 62-62 | 3 | 28,207 | Joe Hesketh | Mark Langston | Mike Fetters | Joe Hesketh | Mark Eichhorn | 546 | 541 | 5 |
| 1991-08-26 | @ OAK | 125 | W 3-0 | 63-62 | 3 | 28,869 | Roger Clemens | Mike Moore | Roger Clemens | Mike Moore | | 549 | 541 | 8 |
| 1991-08-27 | @ OAK | 126 | W 6-4 | 64-62 | 3 | 31,125 | Mike Gardiner | Bob Welch | Mike Gardiner | Bob Welch | Jeff Reardon | 555 | 545 | 10 |
| 1991-08-28 | @ OAK | 127 | L 3-9 | 64-63 | 3 | 34,793 | Matt Young | Dave Stewart | Dave Stewart | Matt Young | | 558 | 554 | 4 |
| 1991-08-30 | @ SEA | 128 | W 3-2 | 65-63 | 3 | 29,889 | Joe Hesketh | Erik Hanson | Joe Hesketh | Erik Hanson | Jeff Reardon | 561 | 556 | 5 |
| 1991-08-31 | @ SEA | 129 | W 4-1 | 66-63 | 3 | 32,840 | Roger Clemens | Bill Krueger | Roger Clemens | Bill Krueger | | 565 | 557 | 8 |
| 1991-09-01 | @ SEA | 130 | W 13-2 | 67-63 | 3 | 19,141 | Kevin Morton | Randy Johnson | Kevin Morton | Randy Johnson | | 578 | 559 | 19 |
| 1991-09-03 | vs CAL | 131 | L 0-2 | 67-64 | 3 | 31,179 | Mike Gardiner | Mark Langston | Mark Langston | Mike Gardiner | Bryan Harvey | 578 | 561 | 17 |
| 1991-09-04 | vs CAL | 132 | W 2-0 | 68-64 | 3 | 29,600 | Joe Hesketh | Kirk McCaskill | Joe Hesketh | Kirk McCaskill | Jeff Reardon | 580 | 561 | 19 |
| 1991-09-05 | vs SEA | 133 | W 4-3 | 69-64 | 3 | 30,200 | Roger Clemens | Erik Hanson | Jeff Reardon | Rob Murphy | | 584 | 564 | 20 |
| 1991-09-06 | vs SEA | 134 | W 6-5 | 70-64 | 3 | 33,002 | Matt Young | Bill Krueger | Dennis Lamp | Michael Jackson | Jeff Reardon | 590 | 569 | 21 |
| 1991-09-07 | vs SEA | 135 | W 11-10 | 71-64 | 3 | 33,119 | Kevin Morton | Randy Johnson | Tom Bolton | Calvin Jones | Jeff Reardon | 601 | 579 | 22 |
| 1991-09-08 | vs SEA | 136 | W 17-6 | 72-64 | 2 | 32,979 | Mike Gardiner | Rich DeLucia | Mike Gardiner | Rich DeLucia | | 618 | 585 | 33 |
| 1991-09-09 | @ CLE | 137 | W 4-3 | 73-64 | 2 | 1,695 | Joe Hesketh | Willie Blair | Greg Harris | Shawn Hillegas | Jeff Reardon | 622 | 588 | 34 |
| 1991-09-10 | @ DET | 138 | W 4-0 | 74-64 | 2 | 16,859 | Roger Clemens | Frank Tanana | Roger Clemens | Frank Tanana | | 626 | 588 | 38 |
| 1991-09-11 | @ DET | 139 | L 2-8 | 74-65 | 2 | 16,710 | Matt Young | Walt Terrell | Walt Terrell | Matt Young | | 628 | 596 | 32 |
| 1991-09-12 | @ NYA | 140 | W 7-2 | 75-65 | 2 | 19,312 | Kevin Morton | Pascual Perez | Kevin Morton | Pascual Perez | | 635 | 598 | 37 |
| 1991-09-13 | @ NYA | 141 | W 5-4 | 76-65 | 2 | 27,831 | Mike Gardiner | Jeff Johnson | Mike Gardiner | Jeff Johnson | Jeff Reardon | 640 | 602 | 38 |
| 1991-09-14 | @ NYA | 142 | L 1-3 | 76-66 | 2 | 45,758 | Joe Hesketh | Scott Sanderson | Scott Sanderson | Joe Hesketh | Steve Farr | 641 | 605 | 36 |
| 1991-09-15 | @ NYA | 143 | W 5-4 | 77-66 | 2 | 22,303 | Roger Clemens | Eric Plunk | Roger Clemens | Lee Guetterman | Jeff Reardon | 646 | 609 | 37 |
| 1991-09-16 | vs BAL | 144 | L 2-9 | 77-67 | 2 | 31,977 | Tom Bolton | Mike Mussina | Mike Mussina | Tom Bolton | | 648 | 618 | 30 |
| 1991-09-17 | vs BAL | 145 | W 4-3 | 78-67 | 2 | 32,657 | Kevin Morton | Jose Mesa | Kevin Morton | Jose Mesa | Jeff Reardon | 652 | 621 | 31 |
| 1991-09-18 | vs BAL | 146 | W 7-5 | 79-67 | 2 | 32,021 | Mike Gardiner | Dave Johnson | Mike Gardiner | Dave Johnson | Greg Harris | 659 | 626 | 33 |
| 1991-09-20 | vs NYA | 147 | W 2-0 | 80-67 | 2 | 34,535 | Roger Clemens | Scott Sanderson | Roger Clemens | Scott Sanderson | | 661 | 626 | 35 |
| 1991-09-21 | vs NYA | 148 | W 12-1 | 81-67 | 2 | 34,520 | Joe Hesketh | Wade Taylor | Joe Hesketh | Wade Taylor | | 673 | 627 | 46 |
| 1991-09-22 | vs NYA | 149 | L 5-7 | 81-68 | 2 | 34,514 | Kevin Morton | Pascual Perez | Steve Farr | Matt Young | | 678 | 634 | 44 |
| 1991-09-23 | @ BAL | 150 | L 3-4 | 81-69 | 2 | 27,349 | Mike Gardiner | Jose Mesa | Jim Poole | Mike Gardiner | Gregg Olson | 681 | 638 | 43 |
| 1991-09-26 | @ BAL | 151 | W 2-1 | 82-70 | 2 | 0 | Roger Clemens | Dave Johnson | Roger Clemens | Dave Johnson | | 683 | 639 | 44 |
| 1991-09-26 | @ BAL | 152 | L 5-6 | 82-70 | 2 | 10,728 | Joe Hesketh | Bob Milacki | Todd Frohwirth | Greg Harris | | 688 | 645 | 43 |
| 1991-09-27 | @ MIL | 153 | L 5-7 | 82-71 | 2 | 11,944 | Kevin Morton | Chris Bosio | Chris Bosio | Kevin Morton | Julio Machado | 693 | 652 | 41 |
| 1991-09-28 | @ MIL | 154 | L 1-4 | 82-72 | 2 | 14,856 | Mike Gardiner | Jaime Navarro | Jaime Navarro | Mike Gardiner | Doug Henry | 694 | 656 | 38 |
| 1991-09-29 | @ MIL | 155 | L 4-5 | 82-73 | 2 | 12,063 | Tom Bolton | Cal Eldred | Julio Machado | Jeff Reardon | Doug Henry | 698 | 661 | 37 |
| 1991-09-30 | @ MIL | 156 | W 9-8 | 83-73 | 2 | 9,333 | Greg Harris | Dan Plesac | Dennis Lamp | Mike Ignasiak | Dan Petry | 707 | 669 | 38 |
| 1991-10-01 | vs DET | 157 | L 5-8 | 83-74 | 2 | 31,942 | Roger Clemens | Frank Tanana | Frank Tanana | Roger Clemens | | 712 | 677 | 35 |
| 1991-10-02 | vs DET | 158 | W 5-3 | 84-74 | 2 | 32,003 | Joe Hesketh | Walt Terrell | Joe Hesketh | Walt Terrell | Tony Fossas | 717 | 680 | 37 |
| 1991-10-03 | vs DET | 159 | L 5-10 | 84-75 | 2 | 31,162 | Kevin Morton | Bill Gullickson | Bill Gullickson | Kevin Morton | | 722 | 690 | 32 |
| 1991-10-04 | vs MIL | 160 | L 2-3 | 84-76 | 2 | 31,894 | Mike Gardiner | Cal Eldred | Cal Eldred | Mike Gardiner | Doug Henry | 724 | 693 | 31 |
| 1991-10-05 | vs MIL | 161 | L 4-13 | 84-77 | 2 | 32,185 | Tom Bolton | Dan Plesac | Mike Ignasiak | Tom Bolton | | 728 | 706 | 22 |
| 1991-10-06 | vs MIL | 162 | L 3-6 | 84-78 | 2 | 31,837 | Roger Clemens | Bill Wegman | Julio Machado | Roger Clemens | Doug Henry | 731 | 712 | 19 |