| 1988-04-04 | vs DET | 1 | L 3-5 | 0-1 | 5 | 34,781 | Roger Clemens | Jack Morris | Jack Morris | Lee Smith | Mike Henneman | 3 | 5 | -2 |
| 1988-04-06 | vs DET | 2 | W 6-5 | 1-1 | 4 | 16,965 | Bruce Hurst | Doyle Alexander | Dennis Lamp | Guillermo Hernandez | Lee Smith | 9 | 10 | -1 |
| 1988-04-07 | vs DET | 3 | L 6-11 | 1-2 | 6 | 13,807 | Steve Ellsworth | Frank Tanana | Frank Tanana | Steve Ellsworth | | 15 | 21 | -6 |
| 1988-04-08 | @ TEX | 4 | W 4-0 | 2-2 | 4 | 18,470 | Oil Can Boyd | Mike Jeffcoat | Oil Can Boyd | Mike Jeffcoat | | 19 | 21 | -2 |
| 1988-04-09 | @ TEX | 5 | W 2-1 | 3-2 | 3 | 27,527 | Roger Clemens | Charlie Hough | Roger Clemens | Charlie Hough | Lee Smith | 21 | 22 | -1 |
| 1988-04-10 | @ TEX | 6 | L 1-4 | 3-3 | 3 | 14,024 | Jeff Sellers | Paul Kilgus | Paul Kilgus | Jeff Sellers | Mitch Williams | 22 | 26 | -4 |
| 1988-04-12 | vs MIL | 7 | W 3-1 | 4-3 | 3 | 12,045 | Bruce Hurst | Chris Bosio | Bruce Hurst | Chris Bosio | Lee Smith | 25 | 27 | -2 |
| 1988-04-13 | vs MIL | 8 | W 6-3 | 5-3 | 3 | 14,114 | Oil Can Boyd | Juan Nieves | Oil Can Boyd | Juan Nieves | Lee Smith | 31 | 30 | 1 |
| 1988-04-14 | vs MIL | 9 | W 2-0 | 6-3 | 3 | 15,693 | Roger Clemens | Bill Wegman | Roger Clemens | Bill Wegman | | 33 | 30 | 3 |
| 1988-04-15 | vs TEX | 10 | L 2-3 | 6-4 | 3 | 12,369 | Jeff Sellers | Charlie Hough | Charlie Hough | Wes Gardner | | 35 | 33 | 2 |
| 1988-04-16 | vs TEX | 11 | L 0-2 | 6-5 | 4 | 25,936 | Steve Ellsworth | Paul Kilgus | Paul Kilgus | Steve Ellsworth | Mitch Williams | 35 | 35 | 0 |
| 1988-04-17 | vs TEX | 12 | W 15-2 | 7-5 | 4 | 32,243 | Bruce Hurst | Mike Jeffcoat | Bruce Hurst | Mike Jeffcoat | | 50 | 37 | 13 |
| 1988-04-18 | vs TEX | 13 | W 4-3 | 8-5 | 4 | 33,976 | Oil Can Boyd | Bobby Witt | Lee Smith | Mitch Williams | | 54 | 40 | 14 |
| 1988-04-19 | @ DET | 14 | W 7-3 | 9-5 | 3 | 11,920 | Roger Clemens | Jack Morris | Roger Clemens | Jack Morris | | 61 | 43 | 18 |
| 1988-04-21 | @ DET | 15 | W 12-3 | 10-5 | 3 | 13,862 | Steve Ellsworth | Jeff Robinson | Steve Ellsworth | Jeff Robinson | | 73 | 46 | 27 |
| 1988-04-24 | @ MIL | 16 | W 4-0 | 11-5 | 3 | 16,379 | Roger Clemens | Teddy Higuera | Roger Clemens | Teddy Higuera | | 77 | 46 | 31 |
| 1988-04-25 | @ MIL | 17 | W 5-1 | 12-5 | 3 | 11,109 | Bruce Hurst | Bill Wegman | Bruce Hurst | Bill Wegman | | 82 | 47 | 35 |
| 1988-04-28 | @ CHA | 18 | L 0-6 | 12-6 | 2 | 8,204 | Oil Can Boyd | Dave LaPoint | Dave LaPoint | Oil Can Boyd | | 82 | 53 | 29 |
| 1988-04-29 | vs MIN | 19 | W 6-5 | 13-6 | 2 | 32,022 | Roger Clemens | Joe Niekro | Lee Smith | Juan Berenguer | | 88 | 58 | 30 |
| 1988-04-30 | vs MIN | 20 | W 8-3 | 14-6 | 2 | 32,708 | Bruce Hurst | Charlie Lea | Bruce Hurst | Charlie Lea | Wes Gardner | 96 | 61 | 35 |
| 1988-05-01 | vs MIN | 21 | L 0-2 | 14-7 | 2 | 31,124 | Jeff Sellers | Frank Viola | Frank Viola | Jeff Sellers | | 96 | 63 | 33 |
| 1988-05-02 | vs KCA | 22 | L 0-2 | 14-8 | 3 | 20,400 | Steve Ellsworth | Floyd Bannister | Floyd Bannister | Steve Ellsworth | Gene Garber | 96 | 65 | 31 |
| 1988-05-03 | vs KCA | 23 | L 3-9 | 14-9 | 3 | 21,602 | Oil Can Boyd | Bret Saberhagen | Bret Saberhagen | Oil Can Boyd | | 99 | 74 | 25 |
| 1988-05-04 | vs CHA | 24 | L 2-6 | 14-10 | 4 | 21,191 | Roger Clemens | Jack McDowell | Jack McDowell | Roger Clemens | | 101 | 80 | 21 |
| 1988-05-05 | vs CHA | 25 | W 16-3 | 15-10 | 4 | 24,135 | Bruce Hurst | Ricky Horton | Bruce Hurst | Ricky Horton | | 117 | 83 | 34 |
| 1988-05-06 | @ MIN | 26 | L 0-5 | 15-11 | 4 | 29,767 | Jeff Sellers | Frank Viola | Frank Viola | Jeff Sellers | | 117 | 88 | 29 |
| 1988-05-07 | @ MIN | 27 | L 2-5 | 15-12 | 5 | 33,416 | Steve Ellsworth | Bert Blyleven | Bert Blyleven | Steve Ellsworth | | 119 | 93 | 26 |
| 1988-05-08 | @ MIN | 28 | W 10-6 | 16-12 | 5 | 28,896 | Oil Can Boyd | Allan Anderson | Oil Can Boyd | Mike Mason | | 129 | 99 | 30 |
| 1988-05-09 | @ KCA | 29 | W 2-0 | 17-12 | 4 | 24,806 | Roger Clemens | Mark Gubicza | Roger Clemens | Mark Gubicza | | 131 | 99 | 32 |
| 1988-05-10 | @ KCA | 30 | L 2-7 | 17-13 | 5 | 21,645 | Bruce Hurst | Floyd Bannister | Floyd Bannister | Bruce Hurst | | 133 | 106 | 27 |
| 1988-05-13 | vs SEA | 31 | W 14-8 | 18-13 | 4 | 29,582 | Oil Can Boyd | Mike Campbell | Oil Can Boyd | Mike Campbell | Wes Gardner | 147 | 114 | 33 |
| 1988-05-14 | vs SEA | 32 | W 3-0 | 19-13 | 4 | 33,846 | Roger Clemens | Scott Bankhead | Roger Clemens | Scott Bankhead | | 150 | 114 | 36 |
| 1988-05-15 | vs SEA | 33 | L 7-11 | 19-14 | 4 | 33,109 | Bruce Hurst | Mark Langston | Michael Jackson | Lee Smith | | 157 | 125 | 32 |
| 1988-05-16 | vs OAK | 34 | L 0-3 | 19-15 | 4 | 24,642 | Jeff Sellers | Storm Davis | Storm Davis | Jeff Sellers | Dennis Eckersley | 157 | 128 | 29 |
| 1988-05-17 | vs OAK | 35 | L 7-12 | 19-16 | 4 | 28,407 | Steve Ellsworth | Steve Ontiveros | Steve Ontiveros | Steve Ellsworth | Rick Honeycutt | 164 | 140 | 24 |
| 1988-05-18 | vs OAK | 36 | W 4-1 | 20-16 | 4 | 24,683 | Oil Can Boyd | Dave Stewart | Oil Can Boyd | Dave Stewart | Lee Smith | 168 | 141 | 27 |
| 1988-05-20 | vs CAL | 37 | L 2-4 | 20-17 | 4 | 31,032 | Roger Clemens | Chuck Finley | DeWayne Buice | Roger Clemens | Bryan Harvey | 170 | 145 | 25 |
| 1988-05-21 | vs CAL | 38 | W 8-4 | 21-17 | 4 | 32,180 | Bruce Hurst | Ray Krawczyk | Bruce Hurst | Ray Krawczyk | Lee Smith | 178 | 149 | 29 |
| 1988-05-22 | vs CAL | 39 | W 12-4 | 22-17 | 4 | 32,678 | Jeff Sellers | Willie Fraser | Bob Stanley | Willie Fraser | | 190 | 153 | 37 |
| 1988-05-23 | @ SEA | 40 | L 3-14 | 22-18 | 4 | 15,511 | Oil Can Boyd | Bill Swift | Bill Swift | Oil Can Boyd | | 193 | 167 | 26 |
| 1988-05-24 | @ SEA | 41 | L 1-14 | 22-19 | 4 | 9,473 | Mike Smithson | Mike Campbell | Mike Campbell | Mike Smithson | | 194 | 181 | 13 |
| 1988-05-25 | @ SEA | 42 | W 4-0 | 23-19 | 4 | 17,968 | Roger Clemens | Mark Langston | Roger Clemens | Mark Langston | | 198 | 181 | 17 |
| 1988-05-27 | @ OAK | 43 | L 2-3 | 23-20 | 4 | 32,723 | Bruce Hurst | Curt Young | Curt Young | Bruce Hurst | Dennis Eckersley | 200 | 184 | 16 |
| 1988-05-28 | @ OAK | 44 | L 5-7 | 23-21 | 4 | 43,177 | Oil Can Boyd | Dave Stewart | Rick Honeycutt | Dennis Lamp | Dennis Eckersley | 205 | 191 | 14 |
| 1988-05-29 | @ OAK | 45 | L 4-5 | 23-22 | 5 | 43,427 | Jeff Sellers | Storm Davis | Gene Nelson | Jeff Sellers | Eric Plunk | 209 | 196 | 13 |
| 1988-05-30 | @ CAL | 46 | W 5-2 | 24-22 | 5 | 46,598 | Roger Clemens | Dan Petry | Roger Clemens | Dan Petry | | 214 | 198 | 16 |
| 1988-05-31 | @ CAL | 47 | W 4-3 | 25-22 | 4 | 24,005 | Mike Smithson | Willie Fraser | Mike Smithson | Willie Fraser | | 218 | 201 | 17 |
| 1988-06-02 | vs TOR | 48 | L 4-5 | 25-23 | 4 | 32,144 | Bruce Hurst | Jose Nunez | David Wells | Bruce Hurst | Mark Eichhorn | 222 | 206 | 16 |
| 1988-06-03 | vs TOR | 49 | L 3-6 | 25-24 | 5 | 32,292 | Oil Can Boyd | John Cerutti | Todd Stottlemyre | Oil Can Boyd | Tom Henke | 225 | 212 | 13 |
| 1988-06-04 | vs TOR | 50 | L 2-10 | 25-25 | 5 | 33,067 | Roger Clemens | Jim Clancy | Jim Clancy | Roger Clemens | Duane Ward | 227 | 222 | 5 |
| 1988-06-05 | vs TOR | 51 | L 4-12 | 25-26 | 5 | 33,756 | Jeff Sellers | Dave Stieb | Duane Ward | Mike Smithson | | 231 | 234 | -3 |
| 1988-06-06 | @ NYA | 52 | W 3-2 | 26-26 | 5 | 37,244 | Bruce Hurst | Neil Allen | Bruce Hurst | Neil Allen | Lee Smith | 234 | 236 | -2 |
| 1988-06-07 | @ NYA | 53 | L 3-4 | 26-27 | 5 | 37,081 | Oil Can Boyd | Charles Hudson | Charles Hudson | Oil Can Boyd | Cecilio Guante | 237 | 240 | -3 |
| 1988-06-08 | @ NYA | 54 | W 4-3 | 27-27 | 5 | 42,804 | Roger Clemens | Tommy John | Roger Clemens | Tommy John | Lee Smith | 241 | 243 | -2 |
| 1988-06-10 | @ TOR | 55 | L 0-3 | 27-28 | 5 | 35,201 | Jeff Sellers | Dave Stieb | Dave Stieb | Jeff Sellers | Tom Henke | 241 | 246 | -5 |
| 1988-06-11 | @ TOR | 56 | L 3-4 | 27-29 | 5 | 40,461 | Bruce Hurst | Mike Flanagan | Duane Ward | Dennis Lamp | | 244 | 250 | -6 |
| 1988-06-12 | @ TOR | 57 | W 8-2 | 28-29 | 5 | 40,123 | Oil Can Boyd | John Cerutti | Oil Can Boyd | John Cerutti | | 252 | 252 | 0 |
| 1988-06-13 | vs NYA | 58 | L 6-12 | 28-30 | 5 | 34,288 | Roger Clemens | Richard Dotson | Richard Dotson | Roger Clemens | Cecilio Guante | 258 | 264 | -6 |
| 1988-06-14 | vs NYA | 59 | W 7-3 | 29-30 | 5 | 33,367 | Mike Smithson | Neil Allen | Mike Smithson | Neil Allen | Lee Smith | 265 | 267 | -2 |
| 1988-06-15 | vs NYA | 60 | W 8-3 | 30-30 | 5 | 33,870 | Bruce Hurst | Al Leiter | Bruce Hurst | Al Leiter | | 273 | 270 | 3 |
| 1988-06-16 | @ BAL | 61 | L 4-8 | 30-31 | 5 | 24,499 | Jeff Sellers | Jeff Ballard | Jeff Ballard | John Trautwein | Mark Williamson | 277 | 278 | -1 |
| 1988-06-17 | @ BAL | 62 | L 2-3 | 30-32 | 5 | 34,340 | Oil Can Boyd | Jay Tibbs | Dave J. Schmidt | Dennis Lamp | | 279 | 281 | -2 |
| 1988-06-18 | @ BAL | 63 | W 5-0 | 31-32 | 5 | 32,175 | Roger Clemens | Jose Bautista | Roger Clemens | Jose Bautista | | 284 | 281 | 3 |
| 1988-06-19 | @ BAL | 64 | W 15-7 | 32-32 | 5 | 31,046 | Mike Smithson | Dickie Noles | Wes Gardner | Dickie Noles | | 299 | 288 | 11 |
| 1988-06-20 | @ CLE | 65 | W 14-7 | 33-32 | 5 | 19,870 | Bruce Hurst | Greg Swindell | Bruce Hurst | Greg Swindell | | 313 | 295 | 18 |
| 1988-06-21 | @ CLE | 66 | W 10-6 | 34-32 | 4 | 26,681 | Jeff Sellers | Rick Rodriguez | Bob Stanley | Rick Rodriguez | Lee Smith | 323 | 301 | 22 |
| 1988-06-22 | @ CLE | 67 | L 1-3 | 34-33 | 4 | 18,843 | Oil Can Boyd | John Farrell | John Farrell | Oil Can Boyd | Doug Jones | 324 | 304 | 20 |
| 1988-06-24 | vs BAL | 68 | L 2-6 | 34-34 | 5 | 35,333 | Roger Clemens | Jose Bautista | Jose Bautista | Roger Clemens | | 326 | 310 | 16 |
| 1988-06-25 | vs BAL | 69 | W 10-3 | 35-34 | 4 | 34,573 | Bruce Hurst | Mike Boddicker | Bob Stanley | Mark Williamson | | 336 | 313 | 23 |
| 1988-06-26 | vs BAL | 70 | W 10-1 | 36-34 | 4 | 34,374 | Mike Smithson | Oswaldo Peraza | Mike Smithson | Oswaldo Peraza | | 346 | 314 | 32 |
| 1988-06-27 | vs CLE | 71 | W 9-5 | 37-34 | 4 | 33,318 | Oil Can Boyd | John Farrell | Dennis Lamp | John Farrell | | 355 | 319 | 36 |
| 1988-06-28 | vs CLE | 72 | W 6-1 | 38-34 | 4 | 34,661 | Wes Gardner | Scott Bailes | Wes Gardner | Scott Bailes | | 361 | 320 | 41 |
| 1988-06-29 | vs CLE | 73 | W 5-1 | 39-34 | 3 | 35,035 | Roger Clemens | Tom Candiotti | Roger Clemens | Tom Candiotti | Lee Smith | 366 | 321 | 45 |
| 1988-07-01 | @ KCA | 74 | L 7-8 | 39-35 | 3 | 25,970 | Bruce Hurst | Bret Saberhagen | Jeff Montgomery | Steve Ellsworth | Steve Farr | 373 | 329 | 44 |
| 1988-07-02 | @ KCA | 75 | L 1-3 | 39-36 | 4 | 37,098 | Oil Can Boyd | Charlie Leibrandt | Charlie Leibrandt | Oil Can Boyd | Steve Farr | 374 | 332 | 42 |
| 1988-07-03 | @ KCA | 76 | L 2-3 | 39-37 | 4 | 36,220 | Mike Smithson | Mark Gubicza | Jeff Montgomery | Lee Smith | Steve Farr | 376 | 335 | 41 |
| 1988-07-04 | @ KCA | 77 | W 9-2 | 40-37 | 3 | 40,804 | Roger Clemens | Ted Power | Roger Clemens | Ted Power | | 385 | 337 | 48 |
| 1988-07-05 | @ MIN | 78 | L 4-6 | 40-38 | 4 | 44,091 | Wes Gardner | Freddie Toliver | Juan Berenguer | Lee Smith | Jeff Reardon | 389 | 343 | 46 |
| 1988-07-06 | @ MIN | 79 | L 1-8 | 40-39 | 4 | 41,027 | Bruce Hurst | Frank Viola | Frank Viola | Bruce Hurst | | 390 | 351 | 39 |
| 1988-07-07 | @ MIN | 80 | W 4-3 | 41-39 | 4 | 32,724 | Oil Can Boyd | Charlie Lea | Oil Can Boyd | Charlie Lea | Bob Stanley | 394 | 354 | 40 |
| 1988-07-08 | @ CHA | 81 | L 5-6 | 42-40 | 4 | 0 | Mike Smithson | Jerry Reuss | John Davis | Mike Smithson | Bobby Thigpen | 399 | 360 | 39 |
| 1988-07-08 | @ CHA | 82 | W 10-7 | 42-40 | 4 | 18,963 | Steve Ellsworth | Bill Long | Dennis Lamp | Bill Long | | 409 | 367 | 42 |
| 1988-07-09 | @ CHA | 83 | L 7-8 | 43-41 | 4 | 0 | Wes Gardner | Melido Perez | Melido Perez | Tom Bolton | Bobby Thigpen | 416 | 375 | 41 |
| 1988-07-09 | @ CHA | 84 | W 8-2 | 43-41 | 4 | 23,699 | Roger Clemens | Jeff Bittiger | Lee Smith | Ricky Horton | | 424 | 377 | 47 |
| 1988-07-10 | @ CHA | 85 | L 1-4 | 43-42 | 4 | 15,163 | Steve Curry | Dave LaPoint | Dave LaPoint | Steve Curry | Bobby Thigpen | 425 | 381 | 44 |
| 1988-07-15 | vs KCA | 86 | W 3-1 | 45-42 | 3 | 0 | Roger Clemens | Bret Saberhagen | Roger Clemens | Bret Saberhagen | | 428 | 382 | 46 |
| 1988-07-15 | vs KCA | 87 | W 7-4 | 45-42 | 3 | 35,412 | Mike Smithson | Charlie Leibrandt | Mike Smithson | Charlie Leibrandt | Lee Smith | 435 | 386 | 49 |
| 1988-07-16 | vs KCA | 88 | W 7-6 | 46-42 | 3 | 34,466 | Oil Can Boyd | Mark Gubicza | Lee Smith | Steve Farr | | 442 | 392 | 50 |
| 1988-07-17 | vs KCA | 89 | W 10-8 | 47-42 | 3 | 34,181 | Wes Gardner | Ted Power | Wes Gardner | Ted Power | | 452 | 400 | 52 |
| 1988-07-18 | vs MIN | 90 | W 6-5 | 48-42 | 3 | 33,397 | Steve Curry | Bert Blyleven | Dennis Lamp | Bert Blyleven | Lee Smith | 458 | 405 | 53 |
| 1988-07-19 | vs MIN | 91 | W 5-0 | 49-42 | 3 | 32,036 | Mike Smithson | Allan Anderson | Mike Smithson | Allan Anderson | | 463 | 405 | 58 |
| 1988-07-20 | vs MIN | 92 | W 9-7 | 50-42 | 3 | 35,313 | Roger Clemens | Charlie Lea | Tom Bolton | Keith Atherton | | 472 | 412 | 60 |
| 1988-07-21 | vs CHA | 93 | W 6-1 | 51-42 | 3 | 32,049 | Oil Can Boyd | Jack McDowell | Oil Can Boyd | Jack McDowell | Bob Stanley | 478 | 413 | 65 |
| 1988-07-22 | vs CHA | 94 | W 4-3 | 52-42 | 3 | 33,477 | Wes Gardner | Melido Perez | Wes Gardner | John Davis | Lee Smith | 482 | 416 | 66 |
| 1988-07-23 | vs CHA | 95 | W 11-5 | 53-42 | 3 | 35,129 | Steve Curry | Dave LaPoint | Mike Smithson | Dave LaPoint | | 493 | 421 | 72 |
| 1988-07-24 | vs CHA | 96 | W 3-2 | 54-42 | 3 | 33,394 | Bruce Hurst | Bill Long | Bruce Hurst | Bill Long | Lee Smith | 496 | 423 | 73 |
| 1988-07-25 | @ TEX | 97 | W 2-0 | 55-42 | 3 | 34,175 | Roger Clemens | Charlie Hough | Roger Clemens | Charlie Hough | | 498 | 423 | 75 |
| 1988-07-26 | @ TEX | 98 | L 8-9 | 55-43 | 3 | 20,456 | Oil Can Boyd | Jose Guzman | Craig McMurtry | Tom Bolton | Mitch Williams | 506 | 432 | 74 |
| 1988-07-27 | @ TEX | 99 | W 10-7 | 56-43 | 3 | 17,639 | Wes Gardner | Jeff Russell | Bob Stanley | Mitch Williams | Lee Smith | 516 | 439 | 77 |
| 1988-07-29 | vs MIL | 100 | W 6-4 | 58-43 | 3 | 0 | Bruce Hurst | Bill Wegman | Bruce Hurst | Bill Wegman | Lee Smith | 522 | 443 | 79 |
| 1988-07-29 | vs MIL | 101 | W 5-4 | 58-43 | 3 | 35,169 | Mike Smithson | Tom Filer | Dennis Lamp | Chris Bosio | Bob Stanley | 527 | 447 | 80 |
| 1988-07-30 | vs MIL | 102 | W 3-2 | 59-43 | 3 | 33,964 | Roger Clemens | Teddy Higuera | Roger Clemens | Teddy Higuera | | 530 | 449 | 81 |
| 1988-07-31 | vs MIL | 103 | W 5-0 | 60-43 | 3 | 33,527 | Mike Boddicker | Don August | Mike Boddicker | Don August | | 535 | 449 | 86 |
| 1988-08-02 | vs TEX | 104 | W 7-2 | 61-43 | 2 | 35,462 | Wes Gardner | Jeff Russell | Wes Gardner | Jeff Russell | | 542 | 451 | 91 |
| 1988-08-03 | vs TEX | 105 | W 5-4 | 62-43 | 1 | 34,380 | Bruce Hurst | Bobby Witt | Dennis Lamp | Bobby Witt | Lee Smith | 547 | 455 | 92 |
| 1988-08-04 | @ DET | 106 | L 6-11 | 62-44 | 2 | 40,980 | Roger Clemens | Walt Terrell | Walt Terrell | Roger Clemens | | 553 | 466 | 87 |
| 1988-08-05 | @ DET | 107 | L 1-3 | 62-46 | 2 | 0 | Mike Smithson | Jack Morris | Jack Morris | Bob Stanley | Mike Henneman | 554 | 469 | 85 |
| 1988-08-05 | @ DET | 108 | L 2-3 | 62-46 | 2 | 44,334 | Mike Boddicker | Eric King | Eric King | Mike Boddicker | Mike Henneman | 556 | 472 | 84 |
| 1988-08-06 | @ DET | 109 | L 2-4 | 62-47 | 3 | 44,838 | Wes Gardner | Doyle Alexander | Doyle Alexander | Wes Gardner | | 558 | 476 | 82 |
| 1988-08-07 | @ DET | 110 | W 3-0 | 63-47 | 3 | 41,623 | Bruce Hurst | Jeff Robinson | Bruce Hurst | Jeff Robinson | | 561 | 476 | 85 |
| 1988-08-09 | @ MIL | 111 | L 2-3 | 64-48 | 2 | 0 | Roger Clemens | Juan Nieves | Chuck Crim | Roger Clemens | | 563 | 479 | 84 |
| 1988-08-09 | @ MIL | 112 | W 5-1 | 64-48 | 2 | 20,816 | Mike Boddicker | Bill Wegman | Mike Boddicker | Bill Wegman | Bob Stanley | 568 | 480 | 88 |
| 1988-08-10 | @ MIL | 113 | L 3-8 | 64-49 | 2 | 19,739 | Mike Smithson | Teddy Higuera | Teddy Higuera | Mike Smithson | | 571 | 488 | 83 |
| 1988-08-11 | @ MIL | 114 | L 0-4 | 64-50 | 2 | 32,351 | Wes Gardner | Don August | Don August | Wes Gardner | | 571 | 492 | 79 |
| 1988-08-12 | vs DET | 115 | W 9-4 | 65-50 | 2 | 34,732 | Bruce Hurst | Doyle Alexander | Bruce Hurst | Doyle Alexander | Bob Stanley | 580 | 496 | 84 |
| 1988-08-13 | vs DET | 116 | W 16-4 | 66-50 | 2 | 33,601 | Mike Boddicker | Jeff Robinson | Mike Boddicker | Jeff Robinson | Tom Bolton | 596 | 500 | 96 |
| 1988-08-14 | vs DET | 117 | L 6-18 | 66-51 | 2 | 33,757 | Roger Clemens | Eric King | Eric King | Roger Clemens | | 602 | 518 | 84 |
| 1988-08-16 | vs SEA | 118 | L 0-7 | 66-52 | 2 | 33,924 | Wes Gardner | Scott Bankhead | Scott Bankhead | Wes Gardner | | 602 | 525 | 77 |
| 1988-08-17 | vs SEA | 119 | W 7-2 | 67-52 | 2 | 31,548 | Bruce Hurst | Bill Swift | Bruce Hurst | Bill Swift | | 609 | 527 | 82 |
| 1988-08-18 | vs SEA | 120 | L 1-6 | 67-53 | 2 | 33,944 | Mike Boddicker | Mark Langston | Mark Langston | Mike Boddicker | | 610 | 533 | 77 |
| 1988-08-19 | vs OAK | 121 | W 7-6 | 68-53 | 2 | 33,993 | Mike Smithson | Dave Stewart | Bob Stanley | Dave Stewart | | 617 | 539 | 78 |
| 1988-08-20 | vs OAK | 122 | W 7-5 | 69-53 | 2 | 34,372 | Oil Can Boyd | Todd Burns | Jeff Sellers | Todd Burns | Lee Smith | 624 | 544 | 80 |
| 1988-08-21 | vs OAK | 123 | L 4-5 | 69-54 | 2 | 33,282 | Wes Gardner | Storm Davis | Rick Honeycutt | Bob Stanley | Dennis Eckersley | 628 | 549 | 79 |
| 1988-08-22 | vs CAL | 124 | W 6-2 | 70-54 | 2 | 33,828 | Bruce Hurst | Terry Clark | Bruce Hurst | Terry Clark | | 634 | 551 | 83 |
| 1988-08-23 | vs CAL | 125 | W 10-2 | 71-54 | 2 | 34,313 | Mike Boddicker | Chuck Finley | Mike Boddicker | Chuck Finley | | 644 | 553 | 91 |
| 1988-08-24 | vs CAL | 126 | L 3-4 | 71-55 | 2 | 32,522 | Roger Clemens | Mike Witt | Mike Witt | Roger Clemens | Bryan Harvey | 647 | 557 | 90 |
| 1988-08-26 | @ SEA | 127 | W 5-3 | 72-55 | 2 | 16,109 | Oil Can Boyd | Scott Bankhead | Oil Can Boyd | Scott Bankhead | Lee Smith | 652 | 560 | 92 |
| 1988-08-27 | @ SEA | 128 | L 6-8 | 72-56 | 2 | 19,706 | Wes Gardner | Terry Taylor | Bill Wilkinson | Tom Bolton | Mike Schooler | 658 | 568 | 90 |
| 1988-08-28 | @ SEA | 129 | W 7-2 | 73-56 | 2 | 17,047 | Bruce Hurst | Mike Moore | Bruce Hurst | Mike Moore | | 665 | 570 | 95 |
| 1988-08-29 | @ OAK | 130 | L 1-3 | 73-57 | 2 | 40,423 | Mike Boddicker | Bob Welch | Bob Welch | Mike Boddicker | Dennis Eckersley | 666 | 573 | 93 |
| 1988-08-30 | @ OAK | 131 | L 0-1 | 73-58 | 2 | 35,220 | Roger Clemens | Dave Stewart | Dave Stewart | Roger Clemens | | 666 | 574 | 92 |
| 1988-08-31 | @ OAK | 132 | L 2-7 | 73-59 | 2 | 37,151 | Mike Smithson | Storm Davis | Storm Davis | Mike Smithson | | 668 | 581 | 87 |
| 1988-09-01 | @ CAL | 133 | W 4-2 | 74-59 | 2 | 27,771 | Wes Gardner | Terry Clark | Wes Gardner | Terry Clark | Lee Smith | 672 | 583 | 89 |
| 1988-09-02 | @ CAL | 134 | L 2-3 | 74-60 | 2 | 29,325 | Bruce Hurst | Chuck Finley | Chuck Finley | Bruce Hurst | Bryan Harvey | 674 | 586 | 88 |
| 1988-09-03 | @ CAL | 135 | L 1-2 | 74-61 | 2 | 33,376 | Mike Boddicker | Mike Witt | Mike Witt | Dennis Lamp | | 675 | 588 | 87 |
| 1988-09-04 | @ CAL | 136 | W 6-5 | 75-61 | 1 | 30,224 | Roger Clemens | Dan Petry | Bob Stanley | Bryan Harvey | Lee Smith | 681 | 593 | 88 |
| 1988-09-05 | @ BAL | 137 | W 4-1 | 76-61 | 1 | 19,614 | Mike Smithson | Dave J. Schmidt | Mike Smithson | Dave J. Schmidt | Lee Smith | 685 | 594 | 91 |
| 1988-09-06 | @ BAL | 138 | W 6-1 | 77-61 | 1 | 19,124 | Wes Gardner | Jay Tibbs | Wes Gardner | Jay Tibbs | | 691 | 595 | 96 |
| 1988-09-07 | @ BAL | 139 | L 3-4 | 77-62 | 1 | 35,569 | Bruce Hurst | Curt Schilling | Mark Thurmond | Bob Stanley | | 694 | 599 | 95 |
| 1988-09-09 | vs CLE | 140 | W 7-4 | 78-62 | 1 | 33,349 | Mike Boddicker | Rich Yett | Mike Boddicker | Rich Yett | Lee Smith | 701 | 603 | 98 |
| 1988-09-10 | vs CLE | 141 | W 6-0 | 79-62 | 1 | 34,099 | Roger Clemens | Buddy Black | Roger Clemens | Buddy Black | | 707 | 603 | 104 |
| 1988-09-11 | vs CLE | 142 | L 2-4 | 79-63 | 1 | 33,154 | Wes Gardner | Tom Candiotti | Tom Candiotti | Bob Stanley | Doug Jones | 709 | 607 | 102 |
| 1988-09-12 | vs BAL | 143 | W 6-1 | 80-63 | 1 | 32,619 | Bruce Hurst | Curt Schilling | Bruce Hurst | Curt Schilling | | 715 | 608 | 107 |
| 1988-09-13 | vs BAL | 144 | W 6-4 | 81-63 | 1 | 32,842 | Mike Smithson | Pete Harnisch | Mike Smithson | Pete Harnisch | Lee Smith | 721 | 612 | 109 |
| 1988-09-14 | vs BAL | 145 | W 4-3 | 82-63 | 1 | 32,745 | Mike Boddicker | Jose Bautista | Mike Boddicker | Jose Bautista | Lee Smith | 725 | 615 | 110 |
| 1988-09-15 | vs NYA | 146 | L 3-5 | 82-64 | 1 | 35,320 | Roger Clemens | Rick Rhoden | Rick Rhoden | Roger Clemens | Dave Righetti | 728 | 620 | 108 |
| 1988-09-16 | vs NYA | 147 | W 7-4 | 83-64 | 1 | 35,226 | Wes Gardner | Al Leiter | Wes Gardner | Steve Shields | Lee Smith | 735 | 624 | 111 |
| 1988-09-17 | vs NYA | 148 | W 3-1 | 84-64 | 1 | 35,051 | Bruce Hurst | Charles Hudson | Bruce Hurst | Charles Hudson | | 738 | 625 | 113 |
| 1988-09-18 | vs NYA | 149 | W 9-4 | 85-64 | 1 | 35,146 | Mike Smithson | Ron Guidry | Mike Smithson | Ron Guidry | Lee Smith | 747 | 629 | 118 |
| 1988-09-19 | @ TOR | 150 | L 4-5 | 85-65 | 1 | 28,455 | Mike Boddicker | Jim Clancy | Jim Clancy | Dennis Lamp | Duane Ward | 751 | 634 | 117 |
| 1988-09-20 | @ TOR | 151 | W 13-2 | 86-65 | 1 | 30,352 | Roger Clemens | Jeff Musselman | Roger Clemens | Jeff Musselman | | 764 | 636 | 128 |
| 1988-09-21 | @ TOR | 152 | L 0-1 | 86-66 | 1 | 30,344 | Wes Gardner | Mike Flanagan | Mike Flanagan | Wes Gardner | Duane Ward | 764 | 637 | 127 |
| 1988-09-23 | @ NYA | 153 | W 10-9 | 87-66 | 1 | 51,511 | Bruce Hurst | Charles Hudson | Dennis Lamp | Dale Mohorcic | Lee Smith | 774 | 646 | 128 |
| 1988-09-24 | @ NYA | 154 | L 4-5 | 87-67 | 1 | 51,392 | Mike Boddicker | Richard Dotson | Lee Guetterman | Lee Smith | | 778 | 651 | 127 |
| 1988-09-25 | @ NYA | 155 | W 6-0 | 88-67 | 1 | 54,774 | Roger Clemens | Rick Rhoden | Roger Clemens | Rick Rhoden | | 784 | 651 | 133 |
| 1988-09-26 | vs TOR | 156 | L 1-11 | 88-68 | 1 | 33,953 | Wes Gardner | Jeff Musselman | Jeff Musselman | Wes Gardner | | 785 | 662 | 123 |
| 1988-09-27 | vs TOR | 157 | L 9-15 | 88-69 | 1 | 34,442 | Mike Smithson | Mike Flanagan | Mike Flanagan | Mike Smithson | | 794 | 677 | 117 |
| 1988-09-28 | vs TOR | 158 | L 0-1 | 88-70 | 1 | 34,873 | Bruce Hurst | Jimmy Key | Jimmy Key | Bruce Hurst | | 794 | 678 | 116 |
| 1988-09-29 | @ CLE | 159 | W 12-0 | 89-70 | 1 | 5,879 | Mike Boddicker | Rod Nichols | Mike Boddicker | Rod Nichols | | 806 | 678 | 128 |
| 1988-09-30 | @ CLE | 160 | L 2-4 | 89-71 | 1 | 15,497 | Roger Clemens | Rich Yett | Rich Yett | Roger Clemens | Doug Jones | 808 | 682 | 126 |
| 1988-10-01 | @ CLE | 161 | L 0-1 | 89-72 | 1 | 14,972 | Jeff Sellers | John Farrell | John Farrell | Jeff Sellers | Doug Jones | 808 | 683 | 125 |
| 1988-10-02 | @ CLE | 162 | L 5-6 | 89-73 | 1 | 10,456 | Mike Boddicker | Tom Candiotti | Tom Candiotti | Dennis Lamp | Buddy Black | 813 | 689 | 124 |