| 1988-04-04 | vs CAL | 1 | W 8-5 | 1-0 | 1 | 35,899 | Ricky Horton | Mike Witt | Ricky Horton | Mike Witt | Bobby Thigpen | 8 | 5 | 3 |
| 1988-04-06 | vs CAL | 2 | L 2-4 | 1-1 | 2 | 7,107 | Jack McDowell | Dan Petry | Donnie Moore | Bobby Thigpen | | 10 | 9 | 1 |
| 1988-04-07 | vs CAL | 3 | W 2-1 | 2-1 | 1 | 8,206 | Dave LaPoint | Chuck Finley | Dave LaPoint | Chuck Finley | Bill Long | 12 | 10 | 2 |
| 1988-04-08 | vs SEA | 4 | W 3-2 | 3-1 | 1 | 10,524 | Melido Perez | Mike Campbell | John Davis | Bill Wilkinson | | 15 | 12 | 3 |
| 1988-04-09 | vs SEA | 5 | L 2-3 | 3-2 | 2 | 15,826 | Ricky Horton | Mark Langston | Jerry Reed | Ricky Horton | | 17 | 15 | 2 |
| 1988-04-10 | vs SEA | 6 | L 4-7 | 3-3 | 2 | 16,814 | Jerry Reuss | Mike Moore | Mike Moore | Jerry Reuss | | 21 | 22 | -1 |
| 1988-04-12 | @ CAL | 7 | L 6-15 | 3-4 | 5 | 23,149 | Jack McDowell | Dan Petry | Dan Petry | Jack McDowell | | 27 | 37 | -10 |
| 1988-04-13 | @ CAL | 8 | L 2-5 | 3-5 | 6 | 22,765 | Dave LaPoint | Chuck Finley | Chuck Finley | Dave LaPoint | DeWayne Buice | 29 | 42 | -13 |
| 1988-04-15 | @ OAK | 9 | W 11-3 | 4-5 | 4 | 16,237 | Ricky Horton | Bob Welch | Ricky Horton | Bob Welch | | 40 | 45 | -5 |
| 1988-04-16 | @ OAK | 10 | W 5-1 | 5-5 | 3 | 30,087 | Melido Perez | Storm Davis | Melido Perez | Storm Davis | Bobby Thigpen | 45 | 46 | -1 |
| 1988-04-17 | @ OAK | 11 | W 7-6 | 6-5 | 1 | 45,150 | Jack McDowell | Steve Ontiveros | Jack McDowell | Steve Ontiveros | Bobby Thigpen | 52 | 52 | 0 |
| 1988-04-18 | @ SEA | 12 | W 4-0 | 7-5 | 1 | 11,213 | Dave LaPoint | Mike Campbell | Dave LaPoint | Mike Campbell | | 56 | 52 | 4 |
| 1988-04-19 | @ SEA | 13 | W 7-2 | 8-5 | 1 | 7,652 | Jerry Reuss | Mark Langston | Jerry Reuss | Mark Langston | | 63 | 54 | 9 |
| 1988-04-20 | @ SEA | 14 | L 4-5 | 8-6 | 2 | 8,734 | Ricky Horton | Mike Moore | Mike Moore | Ricky Horton | | 67 | 59 | 8 |
| 1988-04-21 | vs OAK | 15 | L 3-6 | 8-7 | 2 | 7,039 | Melido Perez | Storm Davis | Gene Nelson | Bill Long | Dennis Eckersley | 70 | 65 | 5 |
| 1988-04-22 | vs OAK | 16 | W 7-5 | 9-7 | 2 | 7,230 | Jack McDowell | Steve Ontiveros | John Pawlowski | Eric Plunk | | 77 | 70 | 7 |
| 1988-04-23 | vs OAK | 17 | L 2-3 | 9-8 | 2 | 12,224 | Dave LaPoint | Dave Stewart | Dave Stewart | John Davis | | 79 | 73 | 6 |
| 1988-04-24 | vs OAK | 18 | L 3-5 | 9-9 | 3 | 14,221 | Ricky Horton | Bob Welch | Bob Welch | Ricky Horton | Dennis Eckersley | 82 | 78 | 4 |
| 1988-04-28 | vs BOS | 19 | W 6-0 | 10-9 | 3 | 8,204 | Dave LaPoint | Oil Can Boyd | Dave LaPoint | Oil Can Boyd | | 88 | 78 | 10 |
| 1988-04-29 | vs BAL | 20 | L 0-9 | 10-10 | 3 | 14,059 | Jack McDowell | Mark Williamson | Mark Williamson | Jack McDowell | Dave J. Schmidt | 88 | 87 | 1 |
| 1988-04-30 | vs BAL | 21 | W 4-1 | 11-10 | 3 | 16,078 | Ricky Horton | Mark Thurmond | Ricky Horton | Mark Thurmond | Bobby Thigpen | 92 | 88 | 4 |
| 1988-05-01 | vs BAL | 22 | W 7-3 | 12-10 | 2 | 12,398 | Melido Perez | Mike Morgan | Melido Perez | Mike Morgan | John Davis | 99 | 91 | 8 |
| 1988-05-02 | vs NYA | 23 | L 4-6 | 12-11 | 3 | 14,786 | Jerry Reuss | Tommy John | Tim Stoddard | Bobby Thigpen | John Candelaria | 103 | 97 | 6 |
| 1988-05-03 | vs NYA | 24 | L 1-4 | 12-12 | 3 | 13,293 | Dave LaPoint | Charles Hudson | Charles Hudson | Dave LaPoint | Cecilio Guante | 104 | 101 | 3 |
| 1988-05-04 | @ BOS | 25 | W 6-2 | 13-12 | 3 | 21,191 | Jack McDowell | Roger Clemens | Jack McDowell | Roger Clemens | | 110 | 103 | 7 |
| 1988-05-05 | @ BOS | 26 | L 3-16 | 13-13 | 3 | 24,135 | Ricky Horton | Bruce Hurst | Bruce Hurst | Ricky Horton | | 113 | 119 | -6 |
| 1988-05-07 | @ BAL | 27 | W 11-7 | 14-13 | 2 | 25,846 | Melido Perez | Mike Morgan | Bill Long | Jose Bautista | Bobby Thigpen | 124 | 126 | -2 |
| 1988-05-08 | @ BAL | 28 | L 5-6 | 14-14 | 2 | 19,521 | Dave LaPoint | Jay Tibbs | Doug Sisk | Bobby Thigpen | | 129 | 132 | -3 |
| 1988-05-09 | @ BAL | 29 | W 3-0 | 15-14 | 2 | 12,757 | Jerry Reuss | Mike Boddicker | Jerry Reuss | Mike Boddicker | Bobby Thigpen | 132 | 132 | 0 |
| 1988-05-10 | @ NYA | 30 | L 3-17 | 15-15 | 2 | 18,118 | Ricky Horton | John Candelaria | John Candelaria | Ricky Horton | | 135 | 149 | -14 |
| 1988-05-11 | @ NYA | 31 | L 2-12 | 15-16 | 2 | 21,001 | Jack McDowell | Richard Dotson | Richard Dotson | Jack McDowell | | 137 | 161 | -24 |
| 1988-05-13 | vs TOR | 32 | W 4-1 | 16-16 | 3 | 10,583 | Melido Perez | Todd Stottlemyre | Melido Perez | Todd Stottlemyre | | 141 | 162 | -21 |
| 1988-05-14 | vs TOR | 33 | W 7-5 | 17-16 | 3 | 23,532 | Dave LaPoint | John Cerutti | Dave LaPoint | John Cerutti | Bill Long | 148 | 167 | -19 |
| 1988-05-15 | vs TOR | 34 | W 6-5 | 18-16 | 2 | 13,948 | Jerry Reuss | Jim Clancy | Bobby Thigpen | Mark Eichhorn | | 154 | 172 | -18 |
| 1988-05-16 | vs TOR | 35 | L 1-5 | 18-17 | 2 | 8,310 | Ricky Horton | Dave Stieb | Dave Stieb | Ricky Horton | | 155 | 177 | -22 |
| 1988-05-17 | @ CLE | 36 | L 2-6 | 18-18 | 3 | 9,499 | Jack McDowell | Rich Yett | Rich Yett | Jack McDowell | Doug Jones | 157 | 183 | -26 |
| 1988-05-18 | @ CLE | 37 | L 1-2 | 18-19 | 3 | 8,299 | Melido Perez | Tom Candiotti | Tom Candiotti | Melido Perez | | 158 | 185 | -27 |
| 1988-05-19 | @ CLE | 38 | L 0-1 | 18-20 | 4 | 10,197 | Dave LaPoint | Greg Swindell | Greg Swindell | Bobby Thigpen | | 158 | 186 | -28 |
| 1988-05-20 | vs DET | 39 | L 6-14 | 18-21 | 4 | 19,308 | Jerry Reuss | Frank Tanana | Frank Tanana | Jerry Reuss | | 164 | 200 | -36 |
| 1988-05-21 | vs DET | 40 | L 1-3 | 18-22 | 4 | 21,693 | Jeff Bittiger | Jack Morris | Jack Morris | Jeff Bittiger | Mike Henneman | 165 | 203 | -38 |
| 1988-05-22 | vs DET | 41 | L 1-3 | 18-23 | 5 | 17,628 | Jack McDowell | Walt Terrell | Walt Terrell | Jack McDowell | | 166 | 206 | -40 |
| 1988-05-23 | vs CLE | 42 | W 3-2 | 19-23 | 5 | 8,624 | Melido Perez | Tom Candiotti | Melido Perez | Tom Candiotti | Bobby Thigpen | 169 | 208 | -39 |
| 1988-05-24 | vs CLE | 43 | L 3-4 | 19-24 | 6 | 8,956 | Dave LaPoint | Greg Swindell | Greg Swindell | Dave LaPoint | Doug Jones | 172 | 212 | -40 |
| 1988-05-25 | vs CLE | 44 | L 2-5 | 19-25 | 6 | 9,900 | John Davis | John Farrell | John Farrell | John Davis | | 174 | 217 | -43 |
| 1988-05-27 | @ TOR | 45 | L 3-4 | 19-26 | 6 | 31,454 | Jeff Bittiger | Mike Flanagan | Duane Ward | Bobby Thigpen | | 177 | 221 | -44 |
| 1988-05-28 | @ TOR | 46 | W 3-2 | 20-26 | 6 | 42,420 | Melido Perez | Jose Nunez | Melido Perez | Todd Stottlemyre | Bobby Thigpen | 180 | 223 | -43 |
| 1988-05-29 | @ TOR | 47 | L 2-4 | 20-27 | 6 | 42,057 | Dave LaPoint | John Cerutti | John Cerutti | Dave LaPoint | David Wells | 182 | 227 | -45 |
| 1988-05-31 | @ DET | 48 | W 10-1 | 21-27 | 5 | 13,223 | Jerry Reuss | Frank Tanana | Jerry Reuss | Frank Tanana | | 192 | 228 | -36 |
| 1988-06-01 | @ DET | 49 | L 3-9 | 21-28 | 6 | 13,763 | Jeff Bittiger | Jack Morris | Jack Morris | Jeff Bittiger | Guillermo Hernandez | 195 | 237 | -42 |
| 1988-06-02 | vs TEX | 50 | L 2-10 | 21-29 | 6 | 8,400 | Melido Perez | Charlie Hough | Charlie Hough | Melido Perez | | 197 | 247 | -50 |
| 1988-06-03 | vs TEX | 51 | L 3-9 | 21-30 | 6 | 11,062 | Dave LaPoint | Ray Hayward | Ray Hayward | Dave LaPoint | | 200 | 256 | -56 |
| 1988-06-04 | vs TEX | 52 | W 10-8 | 22-30 | 5 | 17,101 | Jack McDowell | Jeff Russell | Bobby Thigpen | Dale Mohorcic | | 210 | 264 | -54 |
| 1988-06-05 | vs TEX | 53 | W 5-4 | 23-30 | 5 | 16,399 | Jerry Reuss | Paul Kilgus | Jerry Reuss | Paul Kilgus | Bobby Thigpen | 215 | 268 | -53 |
| 1988-06-06 | vs MIN | 54 | L 4-9 | 23-31 | 5 | 12,827 | Joel Davis | Frank Viola | Juan Berenguer | Bill Long | | 219 | 277 | -58 |
| 1988-06-07 | vs MIN | 55 | W 10-8 | 24-31 | 5 | 11,923 | Melido Perez | Charlie Lea | Ricky Horton | Keith Atherton | Bobby Thigpen | 229 | 285 | -56 |
| 1988-06-08 | vs MIN | 56 | L 2-5 | 24-32 | 5 | 11,428 | Dave LaPoint | Les Straker | Juan Berenguer | Dave LaPoint | | 231 | 290 | -59 |
| 1988-06-10 | vs MIL | 57 | W 1-0 | 25-32 | 5 | 18,794 | Jack McDowell | Teddy Higuera | Bill Long | Teddy Higuera | | 232 | 290 | -58 |
| 1988-06-11 | vs MIL | 58 | W 5-3 | 26-32 | 5 | 26,141 | Jerry Reuss | Chris Bosio | Jerry Reuss | Paul Mirabella | Bobby Thigpen | 237 | 293 | -56 |
| 1988-06-12 | vs MIL | 59 | L 2-16 | 26-33 | 5 | 15,445 | Joel Davis | Don August | Don August | Joel Davis | | 239 | 309 | -70 |
| 1988-06-13 | @ MIN | 60 | W 4-1 | 27-33 | 5 | 28,521 | Melido Perez | Les Straker | Melido Perez | Les Straker | Bobby Thigpen | 243 | 310 | -67 |
| 1988-06-14 | @ MIN | 61 | L 1-3 | 27-34 | 5 | 25,527 | Dave LaPoint | Bert Blyleven | Bert Blyleven | Dave LaPoint | Jeff Reardon | 244 | 313 | -69 |
| 1988-06-15 | @ MIN | 62 | L 1-5 | 27-35 | 5 | 25,512 | Jack McDowell | Allan Anderson | Allan Anderson | Jack McDowell | Keith Atherton | 245 | 318 | -73 |
| 1988-06-16 | @ MIL | 63 | W 3-1 | 28-35 | 5 | 17,624 | Jerry Reuss | Chris Bosio | Jerry Reuss | Chris Bosio | Bobby Thigpen | 248 | 319 | -71 |
| 1988-06-17 | @ MIL | 64 | L 2-7 | 28-36 | 5 | 35,657 | Bill Long | Don August | Don August | Bill Long | Chuck Crim | 250 | 326 | -76 |
| 1988-06-18 | @ MIL | 65 | L 3-6 | 28-37 | 5 | 49,015 | Melido Perez | Bill Wegman | Bill Wegman | Melido Perez | Dan Plesac | 253 | 332 | -79 |
| 1988-06-19 | @ MIL | 66 | W 5-0 | 29-37 | 5 | 38,081 | Dave LaPoint | Tom Filer | Dave LaPoint | Tom Filer | | 258 | 332 | -74 |
| 1988-06-20 | vs KCA | 67 | W 5-3 | 30-37 | 5 | 13,973 | Jack McDowell | Charlie Leibrandt | Bobby Thigpen | Jeff Montgomery | | 263 | 335 | -72 |
| 1988-06-21 | vs KCA | 68 | L 2-6 | 30-38 | 5 | 9,769 | Jerry Reuss | Mark Gubicza | Mark Gubicza | Jerry Reuss | | 265 | 341 | -76 |
| 1988-06-22 | vs KCA | 69 | W 5-4 | 31-38 | 5 | 9,668 | Bill Long | Rick Anderson | Bobby Thigpen | Steve Farr | | 270 | 345 | -75 |
| 1988-06-24 | @ TEX | 70 | L 2-5 | 31-39 | 5 | 16,393 | Melido Perez | Charlie Hough | Charlie Hough | Melido Perez | | 272 | 350 | -78 |
| 1988-06-25 | @ TEX | 71 | W 10-5 | 32-39 | 5 | 29,259 | Dave LaPoint | Ray Hayward | Dave LaPoint | Ray Hayward | | 282 | 355 | -73 |
| 1988-06-26 | @ TEX | 72 | W 7-5 | 33-39 | 5 | 21,594 | Jack McDowell | Jeff Russell | Jack McDowell | Jeff Russell | Bobby Thigpen | 289 | 360 | -71 |
| 1988-06-27 | @ KCA | 73 | L 1-2 | 33-40 | 5 | 36,711 | Jerry Reuss | Mark Gubicza | Mark Gubicza | Jerry Reuss | Jerry Gleaton | 290 | 362 | -72 |
| 1988-06-28 | @ KCA | 74 | W 4-3 | 34-40 | 5 | 23,060 | Bill Long | Rick Anderson | Bill Long | Gene Garber | Bobby Thigpen | 294 | 365 | -71 |
| 1988-06-29 | @ KCA | 75 | L 8-9 | 34-41 | 5 | 26,333 | Melido Perez | Floyd Bannister | Floyd Bannister | Melido Perez | Steve Farr | 302 | 374 | -72 |
| 1988-06-30 | vs NYA | 76 | L 3-5 | 34-42 | 5 | 18,168 | Dave LaPoint | Tommy John | Tommy John | Dave LaPoint | Dave Righetti | 305 | 379 | -74 |
| 1988-07-01 | vs NYA | 77 | W 2-1 | 35-42 | 5 | 19,798 | Jack McDowell | Ron Guidry | Bobby Thigpen | Steve Shields | | 307 | 380 | -73 |
| 1988-07-02 | vs NYA | 78 | L 0-4 | 35-43 | 5 | 23,350 | Jerry Reuss | John Candelaria | John Candelaria | Jerry Reuss | | 307 | 384 | -77 |
| 1988-07-03 | vs NYA | 79 | W 4-3 | 36-43 | 5 | 20,509 | Bill Long | Rick Rhoden | Jeff Bittiger | Cecilio Guante | | 311 | 387 | -76 |
| 1988-07-04 | vs BAL | 80 | W 5-1 | 37-43 | 5 | 16,457 | Melido Perez | Jay Tibbs | Melido Perez | Jay Tibbs | | 316 | 388 | -72 |
| 1988-07-05 | vs BAL | 81 | L 1-5 | 37-44 | 5 | 9,920 | Dave LaPoint | Jose Bautista | Jose Bautista | Dave LaPoint | | 317 | 393 | -76 |
| 1988-07-06 | vs BAL | 82 | W 4-1 | 38-44 | 5 | 10,066 | Jack McDowell | Mike Boddicker | Jack McDowell | Mike Boddicker | Ricky Horton | 321 | 394 | -73 |
| 1988-07-08 | vs BOS | 83 | W 6-5 | 39-45 | 5 | 0 | Jerry Reuss | Mike Smithson | John Davis | Mike Smithson | Bobby Thigpen | 327 | 399 | -72 |
| 1988-07-08 | vs BOS | 84 | L 7-10 | 39-45 | 5 | 18,963 | Bill Long | Steve Ellsworth | Dennis Lamp | Bill Long | | 334 | 409 | -75 |
| 1988-07-09 | vs BOS | 85 | W 8-7 | 40-46 | 5 | 0 | Melido Perez | Wes Gardner | Melido Perez | Tom Bolton | Bobby Thigpen | 342 | 416 | -74 |
| 1988-07-09 | vs BOS | 86 | L 2-8 | 40-46 | 5 | 23,699 | Jeff Bittiger | Roger Clemens | Lee Smith | Ricky Horton | | 344 | 424 | -80 |
| 1988-07-10 | vs BOS | 87 | W 4-1 | 41-46 | 4 | 15,163 | Dave LaPoint | Steve Curry | Dave LaPoint | Steve Curry | Bobby Thigpen | 348 | 425 | -77 |
| 1988-07-14 | @ NYA | 88 | L 5-7 | 41-47 | 5 | 28,284 | Jerry Reuss | John Candelaria | John Candelaria | Jerry Reuss | Cecilio Guante | 353 | 432 | -79 |
| 1988-07-15 | @ NYA | 89 | L 3-5 | 41-48 | 5 | 28,166 | Jack McDowell | Rick Rhoden | Rick Rhoden | Jack McDowell | Cecilio Guante | 356 | 437 | -81 |
| 1988-07-16 | @ NYA | 90 | W 7-4 | 42-48 | 5 | 48,102 | Melido Perez | Tommy John | Melido Perez | Tommy John | Bobby Thigpen | 363 | 441 | -78 |
| 1988-07-17 | @ NYA | 91 | L 3-7 | 42-49 | 5 | 38,750 | Dave LaPoint | Ron Guidry | Ron Guidry | Dave LaPoint | Tim Stoddard | 366 | 448 | -82 |
| 1988-07-19 | @ BAL | 92 | L 4-6 | 43-50 | 5 | 0 | Jerry Reuss | Mike Boddicker | Mike Boddicker | Jerry Reuss | Tom Niedenfuer | 370 | 454 | -84 |
| 1988-07-19 | @ BAL | 93 | W 2-0 | 43-50 | 5 | 17,610 | Bill Long | Jay Tibbs | Bill Long | Jay Tibbs | Bobby Thigpen | 372 | 454 | -82 |
| 1988-07-21 | @ BOS | 94 | L 1-6 | 43-51 | 5 | 32,049 | Jack McDowell | Oil Can Boyd | Oil Can Boyd | Jack McDowell | Bob Stanley | 373 | 460 | -87 |
| 1988-07-22 | @ BOS | 95 | L 3-4 | 43-52 | 5 | 33,477 | Melido Perez | Wes Gardner | Wes Gardner | John Davis | Lee Smith | 376 | 464 | -88 |
| 1988-07-23 | @ BOS | 96 | L 5-11 | 43-53 | 6 | 35,129 | Dave LaPoint | Steve Curry | Mike Smithson | Dave LaPoint | | 381 | 475 | -94 |
| 1988-07-24 | @ BOS | 97 | L 2-3 | 43-54 | 6 | 33,394 | Bill Long | Bruce Hurst | Bruce Hurst | Bill Long | Lee Smith | 383 | 478 | -95 |
| 1988-07-25 | vs SEA | 98 | W 6-5 | 44-54 | 6 | 11,434 | Jerry Reuss | Mike Moore | Jerry Reuss | Mike Moore | Bobby Thigpen | 389 | 483 | -94 |
| 1988-07-26 | vs SEA | 99 | W 1-0 | 45-54 | 6 | 11,551 | Jack McDowell | Scott Bankhead | Ricky Horton | Mike Schooler | | 390 | 483 | -93 |
| 1988-07-27 | vs SEA | 100 | W 6-1 | 46-54 | 5 | 15,033 | Melido Perez | Bill Swift | Melido Perez | Bill Swift | | 396 | 484 | -88 |
| 1988-07-28 | vs CAL | 101 | L 6-7 | 46-55 | 5 | 14,527 | Dave LaPoint | Chuck Finley | Donnie Moore | Ricky Horton | | 402 | 491 | -89 |
| 1988-07-29 | vs CAL | 102 | L 2-4 | 46-56 | 6 | 16,802 | Bill Long | Willie Fraser | Willie Fraser | Bill Long | Bryan Harvey | 404 | 495 | -91 |
| 1988-07-30 | vs CAL | 103 | L 14-15 | 46-57 | 6 | 17,422 | Jerry Reuss | Kirk McCaskill | Sherman Corbett | John Davis | | 418 | 510 | -92 |
| 1988-07-31 | vs CAL | 104 | L 5-7 | 46-58 | 6 | 13,370 | Jack McDowell | Mike Witt | Mike Witt | Ricky Horton | Greg Minton | 423 | 517 | -94 |
| 1988-08-01 | vs OAK | 105 | L 2-10 | 46-59 | 6 | 18,712 | Melido Perez | Todd Burns | Todd Burns | Melido Perez | | 425 | 527 | -102 |
| 1988-08-02 | vs OAK | 106 | W 7-5 | 47-59 | 5 | 13,383 | Dave LaPoint | Steve Ontiveros | Dave LaPoint | Steve Ontiveros | Bobby Thigpen | 432 | 532 | -100 |
| 1988-08-03 | vs OAK | 107 | L 3-4 | 47-60 | 5 | 19,515 | Bill Long | Bob Welch | Gene Nelson | Bobby Thigpen | Dennis Eckersley | 435 | 536 | -101 |
| 1988-08-05 | @ CAL | 108 | L 5-6 | 48-61 | 6 | 0 | Jack McDowell | Mike Witt | Sherman Corbett | Donn Pall | | 440 | 542 | -102 |
| 1988-08-05 | @ CAL | 109 | W 5-4 | 48-61 | 6 | 43,461 | Jerry Reuss | Willie Fraser | Ricky Horton | Greg Minton | Bobby Thigpen | 445 | 546 | -101 |
| 1988-08-06 | @ CAL | 110 | L 5-7 | 48-62 | 6 | 47,967 | Melido Perez | Terry Clark | Terry Clark | Melido Perez | Greg Minton | 450 | 553 | -103 |
| 1988-08-07 | @ CAL | 111 | W 6-3 | 49-62 | 6 | 29,240 | Dave LaPoint | Chuck Finley | Dave LaPoint | Chuck Finley | Bobby Thigpen | 456 | 556 | -100 |
| 1988-08-08 | @ OAK | 112 | L 5-9 | 49-63 | 6 | 25,111 | Bill Long | Bob Welch | Bob Welch | Bill Long | Dennis Eckersley | 461 | 565 | -104 |
| 1988-08-09 | @ OAK | 113 | L 1-8 | 49-64 | 6 | 15,811 | Jeff Bittiger | Dave Stewart | Dave Stewart | Jeff Bittiger | | 462 | 573 | -111 |
| 1988-08-10 | @ OAK | 114 | L 1-2 | 49-65 | 6 | 26,694 | Jack McDowell | Curt Young | Greg Cadaret | Ricky Horton | | 463 | 575 | -112 |
| 1988-08-11 | @ SEA | 115 | W 4-3 | 50-65 | 6 | 9,056 | Jerry Reuss | Bill Swift | Jerry Reuss | Michael Jackson | Bobby Thigpen | 467 | 578 | -111 |
| 1988-08-12 | @ SEA | 116 | W 7-2 | 51-65 | 6 | 9,065 | Dave LaPoint | Dennis Powell | Dave LaPoint | Dennis Powell | | 474 | 580 | -106 |
| 1988-08-13 | @ SEA | 117 | W 7-4 | 52-65 | 6 | 10,078 | Melido Perez | Mark Langston | Melido Perez | Mark Langston | Ricky Horton | 481 | 584 | -103 |
| 1988-08-14 | @ SEA | 118 | L 0-11 | 52-66 | 6 | 11,994 | Bill Long | Mike Moore | Mike Moore | Bill Long | | 481 | 595 | -114 |
| 1988-08-16 | vs TOR | 119 | W 5-4 | 53-66 | 5 | 15,706 | Jack McDowell | Jimmy Key | Jack McDowell | Jimmy Key | Bobby Thigpen | 486 | 599 | -113 |
| 1988-08-17 | vs TOR | 120 | W 5-1 | 54-66 | 5 | 14,367 | Jerry Reuss | Jim Clancy | Jerry Reuss | Jim Clancy | Steve Rosenberg | 491 | 600 | -109 |
| 1988-08-18 | @ DET | 121 | L 4-6 | 54-67 | 5 | 25,279 | Melido Perez | Jeff Robinson | Mike Henneman | Bobby Thigpen | | 495 | 606 | -111 |
| 1988-08-19 | @ DET | 122 | L 4-5 | 54-68 | 6 | 37,313 | Bill Long | Frank Tanana | Frank Tanana | Bill Long | Guillermo Hernandez | 499 | 611 | -112 |
| 1988-08-20 | @ DET | 123 | L 1-2 | 54-69 | 6 | 43,419 | Jeff Bittiger | Walt Terrell | Walt Terrell | Jeff Bittiger | Guillermo Hernandez | 500 | 613 | -113 |
| 1988-08-21 | @ DET | 124 | L 0-5 | 54-70 | 6 | 39,147 | Jack McDowell | Jack Morris | Jack Morris | Jack McDowell | | 500 | 618 | -118 |
| 1988-08-22 | @ TOR | 125 | L 3-6 | 54-71 | 6 | 30,501 | Jerry Reuss | Dave Stieb | Dave Stieb | Jerry Reuss | | 503 | 624 | -121 |
| 1988-08-23 | @ TOR | 126 | L 2-7 | 54-72 | 6 | 28,443 | Melido Perez | Jim Clancy | Jim Clancy | Melido Perez | Duane Ward | 505 | 631 | -126 |
| 1988-08-24 | @ TOR | 127 | W 6-4 | 55-72 | 6 | 33,385 | Bill Long | Jeff Musselman | Bill Long | Jeff Musselman | Bobby Thigpen | 511 | 635 | -124 |
| 1988-08-26 | vs CLE | 128 | L 6-7 | 55-73 | 6 | 13,334 | Jack McDowell | Greg Swindell | Greg Swindell | Jack McDowell | Doug Jones | 517 | 642 | -125 |
| 1988-08-27 | vs CLE | 129 | W 4-1 | 56-73 | 6 | 18,056 | Jerry Reuss | John Farrell | Jerry Reuss | John Farrell | | 521 | 643 | -122 |
| 1988-08-28 | vs CLE | 130 | L 4-5 | 56-74 | 6 | 18,091 | Melido Perez | Buddy Black | Doug Jones | Barry Jones | | 525 | 648 | -123 |
| 1988-08-29 | vs DET | 131 | W 3-2 | 57-74 | 6 | 14,916 | Bill Long | Steve Searcy | Bill Long | Steve Searcy | Bobby Thigpen | 528 | 650 | -122 |
| 1988-08-30 | vs DET | 132 | W 4-1 | 58-74 | 6 | 11,485 | Jeff Bittiger | Walt Terrell | Jeff Bittiger | Walt Terrell | Barry Jones | 532 | 651 | -119 |
| 1988-08-31 | vs DET | 133 | L 3-9 | 58-75 | 6 | 12,693 | Jack McDowell | Jack Morris | Jack Morris | John Davis | | 535 | 660 | -125 |
| 1988-09-02 | @ CLE | 134 | L 3-4 | 58-76 | 6 | 8,859 | Jerry Reuss | Rod Nichols | Doug Jones | Ken Patterson | | 538 | 664 | -126 |
| 1988-09-04 | @ CLE | 135 | L 2-3 | 59-77 | 6 | 0 | Melido Perez | Buddy Black | Brad Havens | Barry Jones | | 540 | 667 | -127 |
| 1988-09-04 | @ CLE | 136 | W 5-2 | 59-77 | 6 | 11,979 | Bill Long | Rich Yett | Bill Long | Doug Jones | Bobby Thigpen | 545 | 669 | -124 |
| 1988-09-05 | @ MIL | 137 | L 2-5 | 59-78 | 6 | 28,992 | Shawn Hillegas | Don August | Don August | Shawn Hillegas | Juan Nieves | 547 | 674 | -127 |
| 1988-09-07 | @ MIL | 138 | W 7-2 | 60-78 | 6 | 16,407 | Jerry Reuss | Mike Birkbeck | Jerry Reuss | Mike Birkbeck | Bobby Thigpen | 554 | 676 | -122 |
| 1988-09-09 | vs MIN | 139 | L 0-1 | 60-79 | 6 | 11,548 | Bill Long | Freddie Toliver | Freddie Toliver | Bill Long | Jeff Reardon | 554 | 677 | -123 |
| 1988-09-10 | vs MIN | 140 | L 5-6 | 60-80 | 6 | 21,119 | Melido Perez | Frank Viola | Mark Portugal | Steve Rosenberg | German Gonzalez | 559 | 683 | -124 |
| 1988-09-11 | vs MIN | 141 | W 3-2 | 61-80 | 6 | 10,902 | Shawn Hillegas | Bert Blyleven | Shawn Hillegas | Bert Blyleven | Ken Patterson | 562 | 685 | -123 |
| 1988-09-12 | vs MIL | 142 | W 2-1 | 62-80 | 6 | 8,351 | Jerry Reuss | Mike Birkbeck | Barry Jones | Dan Plesac | | 564 | 686 | -122 |
| 1988-09-13 | vs MIL | 143 | L 0-4 | 62-81 | 6 | 8,307 | Ken Patterson | Juan Nieves | Juan Nieves | Ken Patterson | | 564 | 690 | -126 |
| 1988-09-14 | vs MIL | 144 | L 2-4 | 62-82 | 6 | 9,650 | Bill Long | Bill Wegman | Bill Wegman | Bill Long | Paul Mirabella | 566 | 694 | -128 |
| 1988-09-15 | @ MIN | 145 | L 3-10 | 62-83 | 6 | 40,964 | Melido Perez | Frank Viola | Frank Viola | Melido Perez | | 569 | 704 | -135 |
| 1988-09-16 | @ MIN | 146 | L 4-5 | 62-84 | 6 | 42,310 | Shawn Hillegas | Bert Blyleven | Bert Blyleven | Shawn Hillegas | Jeff Reardon | 573 | 709 | -136 |
| 1988-09-17 | @ MIN | 147 | L 1-3 | 62-85 | 6 | 46,439 | Jerry Reuss | Allan Anderson | Allan Anderson | Jerry Reuss | Jeff Reardon | 574 | 712 | -138 |
| 1988-09-18 | @ MIN | 148 | W 8-5 | 63-85 | 6 | 47,172 | Ken Patterson | Les Straker | Tom McCarthy | Mark Portugal | Bobby Thigpen | 582 | 717 | -135 |
| 1988-09-19 | @ TEX | 149 | W 7-3 | 64-85 | 6 | 7,320 | Bill Long | Kevin Brown | Bill Long | Kevin Brown | | 589 | 720 | -131 |
| 1988-09-20 | @ TEX | 150 | L 1-4 | 64-86 | 6 | 8,679 | Melido Perez | Bobby Witt | Bobby Witt | Melido Perez | | 590 | 724 | -134 |
| 1988-09-21 | @ TEX | 151 | W 6-1 | 65-86 | 6 | 8,572 | Shawn Hillegas | Jose Guzman | Shawn Hillegas | Jose Guzman | Bobby Thigpen | 596 | 725 | -129 |
| 1988-09-23 | vs KCA | 152 | W 2-0 | 66-86 | 6 | 11,548 | Jerry Reuss | Bret Saberhagen | Jerry Reuss | Bret Saberhagen | Bobby Thigpen | 598 | 725 | -127 |
| 1988-09-24 | vs KCA | 153 | L 2-6 | 66-87 | 6 | 15,790 | Adam Peterson | Floyd Bannister | Floyd Bannister | Adam Peterson | | 600 | 731 | -131 |
| 1988-09-25 | vs KCA | 154 | W 6-5 | 67-87 | 5 | 10,608 | Ravelo Manzanillo | Charlie Leibrandt | Barry Jones | Israel Sanchez | | 606 | 736 | -130 |
| 1988-09-26 | vs TEX | 155 | L 3-5 | 67-88 | 6 | 6,970 | Melido Perez | Bobby Witt | Bobby Witt | Bobby Thigpen | | 609 | 741 | -132 |
| 1988-09-27 | vs TEX | 156 | W 3-2 | 68-88 | 5 | 7,093 | Shawn Hillegas | Paul Kilgus | Tom McCarthy | Paul Kilgus | | 612 | 743 | -131 |
| 1988-09-28 | vs TEX | 157 | W 3-2 | 69-88 | 5 | 7,959 | Jerry Reuss | Charlie Hough | Jerry Reuss | Charlie Hough | Bobby Thigpen | 615 | 745 | -130 |
| 1988-09-29 | @ KCA | 158 | L 6-7 | 69-89 | 5 | 18,850 | Adam Peterson | Floyd Bannister | Israel Sanchez | Donn Pall | | 621 | 752 | -131 |
| 1988-09-30 | @ KCA | 159 | L 2-4 | 69-90 | 5 | 20,785 | Ravelo Manzanillo | Charlie Leibrandt | Charlie Leibrandt | Ravelo Manzanillo | | 623 | 756 | -133 |
| 1988-10-01 | @ KCA | 160 | W 3-0 | 70-90 | 5 | 28,040 | Melido Perez | Mark Gubicza | Melido Perez | Mark Gubicza | | 626 | 756 | -130 |
| 1988-10-02 | @ KCA | 161 | W 5-1 | 71-90 | 5 | 19,951 | Shawn Hillegas | Bret Saberhagen | Shawn Hillegas | Bret Saberhagen | Tom McCarthy | 631 | 757 | -126 |