| 1991-04-08 | vs BOS | 1 | L 2-6 | 0-1 | 7 | 50,114 | Dave Stieb | Roger Clemens | Roger Clemens | Dave Stieb | | 2 | 6 | -4 |
| 1991-04-09 | vs BOS | 2 | W 4-3 | 1-1 | 5 | 42,211 | Jimmy Key | Greg Harris | Jimmy Key | Greg Harris | Tom Henke | 6 | 9 | -3 |
| 1991-04-10 | vs BOS | 3 | W 5-3 | 2-1 | 2 | 41,164 | Todd Stottlemyre | Matt Young | Mike Timlin | Jeff Gray | Tom Henke | 11 | 12 | -1 |
| 1991-04-11 | vs MIL | 4 | W 7-3 | 3-1 | 1 | 38,286 | David Wells | Ron Robinson | David Wells | Ron Robinson | | 18 | 15 | 3 |
| 1991-04-12 | vs MIL | 5 | W 5-4 | 4-1 | 1 | 43,150 | Denis Boucher | Jaime Navarro | Mike Timlin | Dan Plesac | | 23 | 19 | 4 |
| 1991-04-13 | vs MIL | 6 | L 3-7 | 4-2 | 1 | 49,872 | Dave Stieb | Kevin Brown | Kevin Brown | Dave Stieb | Chuck Crim | 26 | 26 | 0 |
| 1991-04-14 | vs MIL | 7 | W 9-0 | 5-2 | 1 | 47,136 | Jimmy Key | Don August | Jimmy Key | Don August | | 35 | 26 | 9 |
| 1991-04-15 | @ DET | 8 | W 4-3 | 6-2 | 1 | 9,632 | Todd Stottlemyre | Walt Terrell | Todd Stottlemyre | Walt Terrell | Duane Ward | 39 | 29 | 10 |
| 1991-04-16 | @ DET | 9 | L 2-6 | 6-3 | 1 | 10,791 | David Wells | Bill Gullickson | Bill Gullickson | David Wells | Mike Henneman | 41 | 35 | 6 |
| 1991-04-17 | @ DET | 10 | L 4-5 | 6-4 | 1 | 16,355 | Denis Boucher | Steve Searcy | Mike Henneman | Duane Ward | | 45 | 40 | 5 |
| 1991-04-19 | @ MIL | 11 | W 5-2 | 7-4 | 1 | 9,604 | Dave Stieb | Don August | Dave Stieb | Don August | | 50 | 42 | 8 |
| 1991-04-20 | @ MIL | 12 | W 4-2 | 8-4 | 1 | 13,545 | Jimmy Key | Chris Bosio | Jimmy Key | Chris Bosio | Duane Ward | 54 | 44 | 10 |
| 1991-04-21 | @ MIL | 13 | L 8-11 | 8-5 | 1 | 14,920 | Todd Stottlemyre | Kevin Brown | Chuck Crim | Frank Wills | | 62 | 55 | 7 |
| 1991-04-22 | @ BOS | 14 | L 4-6 | 8-6 | 3 | 25,841 | David Wells | Danny Darwin | Dennis Lamp | David Wells | Jeff Reardon | 66 | 61 | 5 |
| 1991-04-23 | @ BOS | 15 | L 0-3 | 8-7 | 3 | 29,904 | Denis Boucher | Roger Clemens | Roger Clemens | Denis Boucher | Jeff Reardon | 66 | 64 | 2 |
| 1991-04-24 | @ BOS | 16 | W 6-1 | 9-7 | 2 | 28,841 | Dave Stieb | Matt Young | Dave Stieb | Matt Young | | 72 | 65 | 7 |
| 1991-04-25 | vs DET | 17 | W 3-2 | 10-7 | 1 | 49,688 | Jimmy Key | Dan Petry | Jimmy Key | Dan Petry | Duane Ward | 75 | 67 | 8 |
| 1991-04-26 | vs DET | 18 | W 5-4 | 11-7 | 1 | 50,170 | Todd Stottlemyre | Walt Terrell | Todd Stottlemyre | Walt Terrell | Duane Ward | 80 | 71 | 9 |
| 1991-04-27 | vs DET | 19 | L 2-4 | 11-8 | 1 | 50,211 | David Wells | Bill Gullickson | Bill Gullickson | David Wells | Mike Henneman | 82 | 75 | 7 |
| 1991-04-28 | vs DET | 20 | W 9-6 | 12-8 | 1 | 50,134 | Denis Boucher | Frank Tanana | Mike Timlin | Mark Leiter | Duane Ward | 91 | 81 | 10 |
| 1991-04-30 | @ TEX | 21 | L 5-8 | 12-9 | 2 | 24,873 | Dave Stieb | Kevin Brown | Rich Gossage | Jim Acker | Jeff Russell | 96 | 89 | 7 |
| 1991-05-01 | @ TEX | 22 | L 0-3 | 12-10 | 4 | 33,439 | Jimmy Key | Nolan Ryan | Nolan Ryan | Jimmy Key | | 96 | 92 | 4 |
| 1991-05-02 | @ KCA | 23 | W 3-1 | 13-10 | 3 | 22,896 | Todd Stottlemyre | Kevin Appier | Todd Stottlemyre | Kevin Appier | Duane Ward | 99 | 93 | 6 |
| 1991-05-03 | @ KCA | 24 | W 5-1 | 14-10 | 3 | 20,809 | David Wells | Storm Davis | David Wells | Storm Davis | | 104 | 94 | 10 |
| 1991-05-04 | @ KCA | 25 | L 5-6 | 14-11 | 3 | 22,628 | Denis Boucher | Bret Saberhagen | Bret Saberhagen | Denis Boucher | Jeff Montgomery | 109 | 100 | 9 |
| 1991-05-05 | @ KCA | 26 | W 3-0 | 15-11 | 2 | 22,588 | Dave Stieb | Tom Gordon | Dave Stieb | Tom Gordon | Duane Ward | 112 | 100 | 12 |
| 1991-05-07 | vs TEX | 27 | L 2-3 | 15-12 | 3 | 44,622 | Jimmy Key | Kenny Rogers | Kenny Rogers | Jimmy Key | Jeff Russell | 114 | 103 | 11 |
| 1991-05-08 | vs TEX | 28 | W 4-2 | 16-12 | 3 | 43,211 | Todd Stottlemyre | Nolan Ryan | Todd Stottlemyre | Nolan Ryan | Duane Ward | 118 | 105 | 13 |
| 1991-05-09 | vs CHA | 29 | W 2-0 | 17-12 | 3 | 47,236 | David Wells | Melido Perez | David Wells | Melido Perez | Duane Ward | 120 | 105 | 15 |
| 1991-05-10 | vs CHA | 30 | L 3-5 | 17-13 | 3 | 50,198 | Denis Boucher | Alex Fernandez | Scott Radinsky | Willie Fraser | | 123 | 110 | 13 |
| 1991-05-11 | vs CHA | 31 | W 5-2 | 18-13 | 2 | 50,206 | Dave Stieb | Charlie Hough | Dave Stieb | Charlie Hough | Duane Ward | 128 | 112 | 16 |
| 1991-05-12 | vs CHA | 32 | W 4-2 | 19-13 | 2 | 50,108 | Jimmy Key | Greg Hibbard | Jimmy Key | Greg Hibbard | Duane Ward | 132 | 114 | 18 |
| 1991-05-13 | vs KCA | 33 | W 4-2 | 20-13 | 2 | 44,275 | Todd Stottlemyre | Storm Davis | Todd Stottlemyre | Storm Davis | Duane Ward | 136 | 116 | 20 |
| 1991-05-14 | vs KCA | 34 | W 4-1 | 21-13 | 2 | 43,357 | David Wells | Mark Gubicza | David Wells | Mark Gubicza | Mike Timlin | 140 | 117 | 23 |
| 1991-05-15 | vs KCA | 35 | L 4-6 | 21-14 | 2 | 50,113 | Denis Boucher | Bret Saberhagen | Bret Saberhagen | Denis Boucher | | 144 | 123 | 21 |
| 1991-05-17 | @ CHA | 36 | L 3-5 | 21-15 | 2 | 30,095 | Dave Stieb | Charlie Hough | Donn Pall | Mike Timlin | Bobby Thigpen | 147 | 128 | 19 |
| 1991-05-18 | @ CHA | 37 | W 9-2 | 22-15 | 2 | 34,861 | Jimmy Key | Greg Hibbard | Jimmy Key | Greg Hibbard | | 156 | 130 | 26 |
| 1991-05-19 | @ CHA | 38 | L 4-5 | 22-16 | 2 | 41,015 | Todd Stottlemyre | Jack McDowell | Ken Patterson | Mike Timlin | Bobby Thigpen | 160 | 135 | 25 |
| 1991-05-20 | @ OAK | 39 | W 1-0 | 23-16 | 2 | 24,631 | David Wells | Bob Welch | David Wells | Bob Welch | Tom Henke | 161 | 135 | 26 |
| 1991-05-21 | @ OAK | 40 | W 11-7 | 24-16 | 2 | 22,738 | Jim Acker | Kirk Dressendorfer | Jim Acker | Kirk Dressendorfer | Mike Timlin | 172 | 142 | 30 |
| 1991-05-22 | @ OAK | 41 | L 1-2 | 24-17 | 2 | 34,028 | Dave Stieb | Mike Moore | Mike Moore | Dave Stieb | Dennis Eckersley | 173 | 144 | 29 |
| 1991-05-24 | @ CAL | 42 | W 3-2 | 25-17 | 2 | 26,408 | Jimmy Key | Chuck Finley | Mike Timlin | Chuck Finley | Tom Henke | 176 | 146 | 30 |
| 1991-05-25 | @ CAL | 43 | L 0-5 | 25-18 | 2 | 36,732 | Todd Stottlemyre | Kirk McCaskill | Kirk McCaskill | Todd Stottlemyre | | 176 | 151 | 25 |
| 1991-05-26 | @ CAL | 44 | L 2-6 | 25-19 | 2 | 45,307 | David Wells | Mark Langston | Mark Langston | David Wells | | 178 | 157 | 21 |
| 1991-05-28 | vs OAK | 45 | L 4-8 | 25-20 | 2 | 50,299 | Jim Acker | Mike Moore | Mike Moore | Jim Acker | Dennis Eckersley | 182 | 165 | 17 |
| 1991-05-29 | vs OAK | 46 | W 8-3 | 26-20 | 2 | 50,262 | Jimmy Key | Joe Slusarski | Jimmy Key | Joe Slusarski | Tom Henke | 190 | 168 | 22 |
| 1991-05-30 | vs OAK | 47 | L 6-8 | 26-21 | 2 | 50,271 | Todd Stottlemyre | Bob Welch | Joe Klink | Duane Ward | Dennis Eckersley | 196 | 176 | 20 |
| 1991-05-31 | vs CAL | 48 | W 5-1 | 27-21 | 2 | 50,252 | David Wells | Mark Langston | David Wells | Mark Langston | | 201 | 177 | 24 |
| 1991-06-01 | vs CAL | 49 | L 8-11 | 27-22 | 2 | 50,255 | Willie Fraser | Scott Lewis | Mark Eichhorn | Willie Fraser | Bryan Harvey | 209 | 188 | 21 |
| 1991-06-02 | vs CAL | 50 | L 2-7 | 27-23 | 2 | 50,261 | Jim Acker | Jim Abbott | Jim Abbott | Jim Acker | | 211 | 195 | 16 |
| 1991-06-03 | @ NYA | 51 | W 5-3 | 28-23 | 1 | 17,003 | Jimmy Key | Tim Leary | Jimmy Key | Tim Leary | Tom Henke | 216 | 198 | 18 |
| 1991-06-04 | @ NYA | 52 | L 3-5 | 28-24 | 1 | 15,955 | Todd Stottlemyre | Scott Sanderson | Scott Sanderson | Todd Stottlemyre | Steve Farr | 219 | 203 | 16 |
| 1991-06-05 | @ NYA | 53 | W 4-1 | 29-24 | 1 | 21,213 | David Wells | Jeff Johnson | David Wells | Jeff Johnson | Tom Henke | 223 | 204 | 19 |
| 1991-06-06 | @ BAL | 54 | L 4-6 | 29-25 | 1 | 26,539 | Jim Acker | Bob Milacki | Bob Milacki | Mike Timlin | Gregg Olson | 227 | 210 | 17 |
| 1991-06-07 | @ BAL | 55 | L 4-6 | 29-26 | 1 | 38,228 | Juan Guzman | Roy Smith | Roy Smith | Juan Guzman | Gregg Olson | 231 | 216 | 15 |
| 1991-06-08 | @ BAL | 56 | W 8-4 | 30-26 | 1 | 45,569 | Jimmy Key | Jeff Robinson | Jimmy Key | Paul Kilgus | | 239 | 220 | 19 |
| 1991-06-09 | @ BAL | 57 | W 3-2 | 31-26 | 1 | 27,783 | Todd Stottlemyre | Jeff Ballard | Todd Stottlemyre | Jeff Ballard | Tom Henke | 242 | 222 | 20 |
| 1991-06-11 | @ CLE | 58 | L 1-2 | 31-27 | 2 | 10,753 | David Wells | Greg Swindell | Shawn Hillegas | Jim Acker | | 243 | 224 | 19 |
| 1991-06-12 | @ CLE | 59 | W 1-0 | 32-27 | 1 | 8,089 | Mike Timlin | Tom Candiotti | Mike Timlin | Tom Candiotti | Tom Henke | 244 | 224 | 20 |
| 1991-06-13 | @ CLE | 60 | W 1-0 | 33-27 | 1 | 8,371 | Jimmy Key | Charles Nagy | Jimmy Key | Charles Nagy | | 245 | 224 | 21 |
| 1991-06-14 | vs BAL | 61 | W 9-1 | 34-27 | 1 | 50,287 | Todd Stottlemyre | Jeff Robinson | Todd Stottlemyre | Jeff Robinson | | 254 | 225 | 29 |
| 1991-06-15 | vs BAL | 62 | L 4-8 | 34-28 | 1 | 50,292 | Juan Guzman | Jeff Ballard | Jeff Ballard | Juan Guzman | Mark Williamson | 258 | 233 | 25 |
| 1991-06-16 | vs BAL | 63 | L 8-13 | 34-29 | 2 | 50,273 | David Wells | Jose Mesa | Todd Frohwirth | Duane Ward | | 266 | 246 | 20 |
| 1991-06-18 | vs NYA | 64 | L 2-4 | 34-30 | 2 | 50,271 | Mike Timlin | Scott Kamieniecki | Scott Kamieniecki | Mike Timlin | Steve Farr | 268 | 250 | 18 |
| 1991-06-19 | vs NYA | 65 | L 0-3 | 34-31 | 2 | 50,281 | Jimmy Key | Jeff Johnson | Jeff Johnson | Jimmy Key | Steve Howe | 268 | 253 | 15 |
| 1991-06-20 | vs NYA | 66 | W 6-1 | 35-31 | 2 | 50,256 | Todd Stottlemyre | Tim Leary | Todd Stottlemyre | Tim Leary | | 274 | 254 | 20 |
| 1991-06-21 | vs CLE | 67 | W 8-4 | 36-31 | 2 | 50,283 | David Wells | Greg Swindell | David Wells | Greg Swindell | Tom Henke | 282 | 258 | 24 |
| 1991-06-22 | vs CLE | 68 | W 4-0 | 37-31 | 2 | 50,285 | Juan Guzman | Jeff Mutis | Juan Guzman | Jeff Mutis | Duane Ward | 286 | 258 | 28 |
| 1991-06-23 | vs CLE | 69 | W 3-1 | 38-31 | 1 | 50,275 | Mike Timlin | Tom Candiotti | Bob Macdonald | Tom Candiotti | Tom Henke | 289 | 259 | 30 |
| 1991-06-24 | vs CLE | 70 | W 4-3 | 39-31 | 1 | 50,263 | Jimmy Key | Charles Nagy | Duane Ward | Charles Nagy | Tom Henke | 293 | 262 | 31 |
| 1991-06-25 | @ MIN | 71 | L 6-8 | 39-32 | 1 | 26,350 | Todd Stottlemyre | Jack Morris | Jack Morris | Todd Stottlemyre | Rick Aguilera | 299 | 270 | 29 |
| 1991-06-26 | @ MIN | 72 | W 5-2 | 40-32 | 1 | 25,503 | David Wells | Mark Guthrie | David Wells | Mark Guthrie | Tom Henke | 304 | 272 | 32 |
| 1991-06-27 | @ MIN | 73 | W 1-0 | 41-32 | 1 | 35,598 | Juan Guzman | Kevin Tapani | Juan Guzman | Kevin Tapani | Tom Henke | 305 | 272 | 33 |
| 1991-06-28 | vs SEA | 74 | L 1-3 | 41-33 | 1 | 50,297 | Tom Candiotti | Bill Krueger | Bill Krueger | Tom Candiotti | Michael Jackson | 306 | 275 | 31 |
| 1991-06-29 | vs SEA | 75 | W 4-0 | 42-33 | 1 | 50,268 | Jimmy Key | Rich DeLucia | Mike Timlin | Rich DeLucia | Duane Ward | 310 | 275 | 35 |
| 1991-06-30 | vs SEA | 76 | W 6-1 | 43-33 | 1 | 50,298 | Todd Stottlemyre | Brian Holman | Todd Stottlemyre | Brian Holman | | 316 | 276 | 40 |
| 1991-07-01 | vs SEA | 77 | W 4-3 | 44-33 | 1 | 50,270 | David Wells | Randy Johnson | Jim Acker | Michael Jackson | | 320 | 279 | 41 |
| 1991-07-02 | vs MIN | 78 | W 4-3 | 45-33 | 1 | 48,676 | Juan Guzman | Kevin Tapani | Duane Ward | Terry Leach | | 324 | 282 | 42 |
| 1991-07-03 | vs MIN | 79 | W 4-0 | 46-33 | 1 | 50,071 | Tom Candiotti | Allan Anderson | Tom Candiotti | Allan Anderson | | 328 | 282 | 46 |
| 1991-07-04 | vs MIN | 80 | L 0-1 | 46-34 | 1 | 50,293 | Jimmy Key | David West | David West | Jimmy Key | Rick Aguilera | 328 | 283 | 45 |
| 1991-07-05 | @ SEA | 81 | W 2-1 | 47-34 | 1 | 21,647 | Todd Stottlemyre | Brian Holman | Bob Macdonald | Brian Holman | Tom Henke | 330 | 284 | 46 |
| 1991-07-06 | @ SEA | 82 | W 4-3 | 48-34 | 1 | 48,570 | David Wells | Randy Johnson | Mike Timlin | Russ Swan | Tom Henke | 334 | 287 | 47 |
| 1991-07-07 | @ SEA | 83 | W 5-2 | 49-34 | 1 | 27,812 | Juan Guzman | Erik Hanson | Juan Guzman | Erik Hanson | | 339 | 289 | 50 |
| 1991-07-11 | vs TEX | 84 | W 2-0 | 50-34 | 1 | 50,276 | Tom Candiotti | Kevin Brown | Tom Candiotti | Kevin Brown | Tom Henke | 341 | 289 | 52 |
| 1991-07-12 | vs TEX | 85 | W 6-2 | 51-34 | 1 | 50,279 | David Wells | Jose Guzman | David Wells | Jose Guzman | Duane Ward | 347 | 291 | 56 |
| 1991-07-13 | vs TEX | 86 | W 3-2 | 52-34 | 1 | 50,270 | Todd Stottlemyre | Nolan Ryan | Mike Timlin | Jeff Russell | Tom Henke | 350 | 293 | 57 |
| 1991-07-14 | vs TEX | 87 | L 6-8 | 52-35 | 1 | 50,294 | Jimmy Key | John Barfield | John Barfield | Jimmy Key | Jeff Russell | 356 | 301 | 55 |
| 1991-07-15 | @ KCA | 88 | W 5-3 | 53-35 | 1 | 29,723 | Juan Guzman | Mike Boddicker | Mike Timlin | Steve Crawford | Tom Henke | 361 | 304 | 57 |
| 1991-07-16 | @ KCA | 89 | L 1-2 | 53-36 | 1 | 22,134 | Tom Candiotti | Kevin Appier | Luis Aquino | Tom Candiotti | | 362 | 306 | 56 |
| 1991-07-18 | @ TEX | 90 | W 4-0 | 54-36 | 1 | 37,268 | David Wells | Nolan Ryan | David Wells | Nolan Ryan | Duane Ward | 366 | 306 | 60 |
| 1991-07-19 | @ TEX | 91 | W 7-2 | 55-36 | 1 | 35,144 | Todd Stottlemyre | John Barfield | Todd Stottlemyre | John Barfield | Mike Timlin | 373 | 308 | 65 |
| 1991-07-20 | @ TEX | 92 | L 6-11 | 55-37 | 1 | 39,276 | Jimmy Key | Terry Mathews | Mike Jeffcoat | Jimmy Key | | 379 | 319 | 60 |
| 1991-07-21 | @ TEX | 93 | L 5-6 | 55-38 | 1 | 31,803 | Juan Guzman | Gerald Alexander | Kenny Rogers | Mike Timlin | Jeff Russell | 384 | 325 | 59 |
| 1991-07-23 | @ CHA | 94 | L 2-3 | 55-39 | 1 | 34,779 | Tom Candiotti | Alex Fernandez | Bobby Thigpen | Tom Candiotti | | 386 | 328 | 58 |
| 1991-07-24 | @ CHA | 95 | W 2-1 | 56-39 | 1 | 39,599 | David Wells | Jack McDowell | David Wells | Jack McDowell | Tom Henke | 388 | 329 | 59 |
| 1991-07-25 | @ CHA | 96 | L 1-7 | 56-40 | 1 | 42,796 | Todd Stottlemyre | Charlie Hough | Charlie Hough | Todd Stottlemyre | | 389 | 336 | 53 |
| 1991-07-26 | vs KCA | 97 | W 6-5 | 57-40 | 1 | 50,326 | Jimmy Key | Mike Boddicker | Duane Ward | Tom Gordon | | 395 | 341 | 54 |
| 1991-07-27 | vs KCA | 98 | L 2-5 | 57-41 | 1 | 50,291 | Juan Guzman | Kevin Appier | Tom Gordon | Mike Timlin | Jeff Montgomery | 397 | 346 | 51 |
| 1991-07-28 | vs KCA | 99 | L 4-10 | 57-42 | 1 | 50,291 | Tom Candiotti | Mark Gubicza | Mark Gubicza | Tom Candiotti | Storm Davis | 401 | 356 | 45 |
| 1991-07-29 | vs CHA | 100 | L 4-12 | 57-43 | 1 | 50,298 | David Wells | Jack McDowell | Jack McDowell | David Wells | | 405 | 368 | 37 |
| 1991-07-30 | vs CHA | 101 | L 7-8 | 57-44 | 1 | 50,291 | Todd Stottlemyre | Charlie Hough | Scott Radinsky | Bob Macdonald | Bobby Thigpen | 412 | 376 | 36 |
| 1991-07-31 | vs CLE | 102 | W 3-1 | 58-44 | 1 | 50,276 | Jimmy Key | Eric King | Jimmy Key | Eric King | Tom Henke | 415 | 377 | 38 |
| 1991-08-01 | vs CLE | 103 | W 7-5 | 59-44 | 1 | 50,275 | Juan Guzman | Charles Nagy | Duane Ward | Jeff Shaw | Tom Henke | 422 | 382 | 40 |
| 1991-08-02 | @ BOS | 104 | L 3-5 | 59-45 | 1 | 34,032 | Tom Candiotti | Roger Clemens | Roger Clemens | Tom Candiotti | | 425 | 387 | 38 |
| 1991-08-03 | @ BOS | 105 | L 1-4 | 59-46 | 1 | 34,015 | David Wells | Joe Hesketh | Joe Hesketh | David Wells | Jeff Reardon | 426 | 391 | 35 |
| 1991-08-04 | @ BOS | 106 | W 2-1 | 60-46 | 1 | 33,809 | Todd Stottlemyre | Greg Harris | Duane Ward | Dennis Lamp | Tom Henke | 428 | 392 | 36 |
| 1991-08-06 | vs DET | 107 | W 2-1 | 61-46 | 1 | 50,305 | Jimmy Key | John Cerutti | Jimmy Key | John Cerutti | Tom Henke | 430 | 393 | 37 |
| 1991-08-07 | vs DET | 108 | W 5-2 | 62-46 | 1 | 50,324 | Juan Guzman | Frank Tanana | Juan Guzman | Frank Tanana | Tom Henke | 435 | 395 | 40 |
| 1991-08-08 | vs DET | 109 | L 0-4 | 62-47 | 1 | 50,307 | Tom Candiotti | Bill Gullickson | Paul Gibson | Tom Henke | | 435 | 399 | 36 |
| 1991-08-09 | vs BOS | 110 | L 7-12 | 62-48 | 1 | 50,319 | David Wells | Joe Hesketh | Joe Hesketh | David Wells | Jeff Reardon | 442 | 411 | 31 |
| 1991-08-10 | vs BOS | 111 | L 1-7 | 62-49 | 1 | 50,304 | Todd Stottlemyre | Greg Harris | Greg Harris | Todd Stottlemyre | | 443 | 418 | 25 |
| 1991-08-11 | vs BOS | 112 | L 6-9 | 62-50 | 1 | 50,297 | Jimmy Key | Mike Gardiner | Mike Gardiner | Jimmy Key | Jeff Reardon | 449 | 427 | 22 |
| 1991-08-12 | vs BOS | 113 | L 8-11 | 62-51 | 1 | 50,305 | Juan Guzman | Roger Clemens | Dennis Lamp | Duane Ward | Jeff Reardon | 457 | 438 | 19 |
| 1991-08-13 | @ MIL | 114 | L 4-5 | 62-52 | 1 | 22,996 | Tom Candiotti | Bill Wegman | Chuck Crim | Tom Henke | | 461 | 443 | 18 |
| 1991-08-14 | @ MIL | 115 | L 3-5 | 62-53 | 1 | 19,193 | David Wells | Chris Bosio | Chris Bosio | David Wells | Doug Henry | 464 | 448 | 16 |
| 1991-08-15 | @ MIL | 116 | W 4-1 | 63-53 | 1 | 24,519 | Todd Stottlemyre | Dan Plesac | Todd Stottlemyre | Dan Plesac | Tom Henke | 468 | 449 | 19 |
| 1991-08-16 | @ DET | 117 | L 2-5 | 63-54 | 1 | 43,186 | Jimmy Key | John Cerutti | John Cerutti | Jimmy Key | Dan Gakeler | 470 | 454 | 16 |
| 1991-08-17 | @ DET | 118 | W 7-5 | 64-54 | 1 | 46,634 | Juan Guzman | Scott Aldred | Bob Macdonald | Scott Aldred | Tom Henke | 477 | 459 | 18 |
| 1991-08-18 | @ DET | 119 | W 4-2 | 65-54 | 1 | 48,724 | Tom Candiotti | Bill Gullickson | Tom Candiotti | Jeff Kaiser | Tom Henke | 481 | 461 | 20 |
| 1991-08-20 | vs MIL | 120 | W 3-1 | 66-54 | 1 | 50,311 | Todd Stottlemyre | Chris Bosio | Todd Stottlemyre | Chris Bosio | Tom Henke | 484 | 462 | 22 |
| 1991-08-21 | vs MIL | 121 | L 0-3 | 66-55 | 1 | 50,306 | Jimmy Key | Dan Plesac | Julio Machado | Jimmy Key | Ed Nunez | 484 | 465 | 19 |
| 1991-08-22 | vs MIL | 122 | L 7-8 | 66-56 | 1 | 50,309 | Juan Guzman | Don August | Mike Ignasiak | Duane Ward | Doug Henry | 491 | 473 | 18 |
| 1991-08-23 | vs NYA | 123 | W 6-5 | 67-56 | 1 | 50,318 | Tom Candiotti | Wade Taylor | Duane Ward | Steve Farr | | 497 | 478 | 19 |
| 1991-08-24 | vs NYA | 124 | L 5-6 | 67-57 | 2 | 50,324 | David Wells | Jeff Johnson | Jeff Johnson | David Wells | Greg Cadaret | 502 | 484 | 18 |
| 1991-08-25 | vs NYA | 125 | W 11-7 | 68-57 | 2 | 50,320 | Todd Stottlemyre | Scott Sanderson | Jim Acker | Lee Guetterman | | 513 | 491 | 22 |
| 1991-08-26 | @ BAL | 126 | W 5-2 | 69-57 | 2 | 28,063 | Jimmy Key | Dave Johnson | Jimmy Key | Dave Johnson | Tom Henke | 518 | 493 | 25 |
| 1991-08-27 | @ BAL | 127 | W 6-1 | 70-57 | 1 | 25,090 | Juan Guzman | Arthur Rhodes | Juan Guzman | Arthur Rhodes | | 524 | 494 | 30 |
| 1991-08-28 | @ BAL | 128 | W 3-0 | 71-57 | 1 | 28,262 | Tom Candiotti | Ben McDonald | Tom Candiotti | Ben McDonald | Tom Henke | 527 | 494 | 33 |
| 1991-08-29 | @ NYA | 129 | W 6-2 | 72-57 | 1 | 19,344 | David Wells | Jeff Johnson | David Wells | Jeff Johnson | | 533 | 496 | 37 |
| 1991-08-30 | @ NYA | 130 | L 2-9 | 72-58 | 1 | 19,393 | Todd Stottlemyre | Scott Sanderson | Scott Sanderson | Todd Stottlemyre | | 535 | 505 | 30 |
| 1991-08-31 | @ NYA | 131 | W 5-0 | 73-58 | 1 | 28,932 | Jimmy Key | Eric Plunk | Jimmy Key | Greg Cadaret | Duane Ward | 540 | 505 | 35 |
| 1991-09-01 | @ NYA | 132 | L 2-4 | 73-59 | 1 | 25,105 | Juan Guzman | Pascual Perez | Lee Guetterman | Bob Macdonald | | 542 | 509 | 33 |
| 1991-09-02 | vs BAL | 133 | W 5-4 | 74-59 | 1 | 50,314 | Tom Candiotti | Dave Johnson | Mike Timlin | Gregg Olson | | 547 | 513 | 34 |
| 1991-09-03 | vs BAL | 134 | L 4-8 | 74-60 | 1 | 50,299 | David Wells | Ben McDonald | Ben McDonald | David Wells | Mike Flanagan | 551 | 521 | 30 |
| 1991-09-04 | vs BAL | 135 | W 3-1 | 75-60 | 1 | 50,303 | Todd Stottlemyre | Bob Milacki | Todd Stottlemyre | Bob Milacki | Duane Ward | 554 | 522 | 32 |
| 1991-09-05 | @ CLE | 136 | W 13-1 | 76-60 | 1 | 5,666 | Jimmy Key | Charles Nagy | Jimmy Key | Charles Nagy | | 567 | 523 | 44 |
| 1991-09-06 | @ CLE | 137 | W 7-4 | 77-60 | 1 | 14,533 | Juan Guzman | Dave Otto | Juan Guzman | Dave Otto | Duane Ward | 574 | 527 | 47 |
| 1991-09-07 | @ CLE | 138 | W 4-1 | 78-60 | 1 | 17,830 | Tom Candiotti | Greg Swindell | Tom Candiotti | Greg Swindell | | 578 | 528 | 50 |
| 1991-09-08 | @ CLE | 139 | W 11-5 | 79-60 | 1 | 13,071 | David Wells | Eric King | David Wells | Eric King | | 589 | 533 | 56 |
| 1991-09-10 | vs SEA | 140 | L 4-5 | 79-61 | 1 | 50,196 | Todd Stottlemyre | Brian Holman | Brian Holman | Todd Stottlemyre | Calvin Jones | 593 | 538 | 55 |
| 1991-09-11 | vs SEA | 141 | L 3-7 | 79-62 | 1 | 50,321 | Jimmy Key | Erik Hanson | Erik Hanson | Jimmy Key | | 596 | 545 | 51 |
| 1991-09-13 | vs OAK | 142 | W 7-6 | 80-62 | 1 | 50,315 | Juan Guzman | Dave Stewart | Juan Guzman | Dave Stewart | Tom Henke | 603 | 551 | 52 |
| 1991-09-14 | vs OAK | 143 | W 6-0 | 81-62 | 1 | 50,319 | Tom Candiotti | Bob Welch | Tom Candiotti | Bob Welch | | 609 | 551 | 58 |
| 1991-09-15 | vs OAK | 144 | L 5-10 | 81-63 | 1 | 50,315 | Todd Stottlemyre | Mike Moore | Mike Moore | Todd Stottlemyre | Dennis Eckersley | 614 | 561 | 53 |
| 1991-09-16 | @ SEA | 145 | L 5-6 | 81-64 | 1 | 55,612 | Jimmy Key | Brian Holman | Russ Swan | Bob Macdonald | | 619 | 567 | 52 |
| 1991-09-17 | @ SEA | 146 | L 4-5 | 81-65 | 1 | 29,115 | Juan Guzman | Erik Hanson | Mike Schooler | Jim Acker | | 623 | 572 | 51 |
| 1991-09-18 | @ SEA | 147 | W 5-3 | 82-65 | 1 | 30,200 | Tom Candiotti | Randy Johnson | Duane Ward | Scott Bankhead | Jim Acker | 628 | 575 | 53 |
| 1991-09-20 | @ OAK | 148 | L 5-6 | 82-66 | 1 | 33,765 | Todd Stottlemyre | Bob Welch | Dennis Eckersley | Duane Ward | | 633 | 581 | 52 |
| 1991-09-21 | @ OAK | 149 | L 0-4 | 82-67 | 1 | 36,601 | Jimmy Key | Mike Moore | Mike Moore | Jimmy Key | | 633 | 585 | 48 |
| 1991-09-22 | @ OAK | 150 | W 3-2 | 83-67 | 1 | 28,276 | Juan Guzman | Ron Darling | Juan Guzman | Ron Darling | David Wells | 636 | 587 | 49 |
| 1991-09-23 | @ CAL | 151 | L 9-10 | 83-68 | 1 | 20,001 | Tom Candiotti | Chuck Finley | Scott Lewis | Tom Candiotti | Bryan Harvey | 645 | 597 | 48 |
| 1991-09-24 | @ CAL | 152 | W 3-0 | 84-68 | 1 | 21,538 | Todd Stottlemyre | Jim Abbott | David Wells | Jim Abbott | | 648 | 597 | 51 |
| 1991-09-25 | @ CAL | 153 | W 7-2 | 85-68 | 1 | 19,251 | Jimmy Key | Mark Langston | Jimmy Key | Mark Langston | | 655 | 599 | 56 |
| 1991-09-27 | vs MIN | 154 | W 7-2 | 86-68 | 1 | 50,326 | Juan Guzman | Kevin Tapani | Juan Guzman | Kevin Tapani | | 662 | 601 | 61 |
| 1991-09-28 | vs MIN | 155 | L 0-5 | 86-69 | 1 | 50,319 | Tom Candiotti | Jack Morris | Jack Morris | Tom Candiotti | | 662 | 606 | 56 |
| 1991-09-29 | vs MIN | 156 | W 2-1 | 87-69 | 1 | 50,315 | Todd Stottlemyre | Scott Erickson | Todd Stottlemyre | Scott Erickson | Duane Ward | 664 | 607 | 57 |
| 1991-09-30 | vs CAL | 157 | L 1-2 | 87-70 | 1 | 50,321 | Jimmy Key | Mark Langston | Mark Langston | Jimmy Key | Bryan Harvey | 665 | 609 | 56 |
| 1991-10-01 | vs CAL | 158 | W 5-2 | 88-70 | 1 | 50,322 | Juan Guzman | Mike Fetters | Juan Guzman | Mike Fetters | Duane Ward | 670 | 611 | 59 |
| 1991-10-02 | vs CAL | 159 | W 6-5 | 89-70 | 1 | 50,324 | Tom Candiotti | Joe Grahe | Mike Timlin | Bryan Harvey | | 676 | 616 | 60 |
| 1991-10-04 | @ MIN | 160 | W 4-1 | 90-70 | 1 | 35,124 | Todd Stottlemyre | Denny Neagle | Todd Stottlemyre | Denny Neagle | Duane Ward | 680 | 617 | 63 |
| 1991-10-05 | @ MIN | 161 | L 1-3 | 90-71 | 1 | 51,058 | Juan Guzman | Scott Erickson | Scott Erickson | Juan Guzman | Rick Aguilera | 681 | 620 | 61 |
| 1991-10-06 | @ MIN | 162 | W 3-2 | 91-71 | 1 | 37,794 | Pat Hentgen | Tom Edens | David Weathers | Allan Anderson | Duane Ward | 684 | 622 | 62 |