| 1980-04-11 | vs CLE | 1 | W 10-2 | 1-0 | 2 | 37,085 | Dave Frost | Dan Spillner | Dave Frost | Dan Spillner | | 10 | 2 | 8 |
| 1980-04-12 | vs CLE | 2 | L 1-2 | 1-1 | 6 | 32,353 | Bruce Kison | Len Barker | Len Barker | Bruce Kison | Sid Monge | 11 | 4 | 7 |
| 1980-04-13 | vs CLE | 3 | W 8-3 | 2-1 | 4 | 33,628 | Don Aase | John Denny | Don Aase | John Denny | John Montague | 19 | 7 | 12 |
| 1980-04-14 | vs MIN | 4 | L 3-5 | 2-2 | 6 | 24,944 | Chris Knapp | Terry Felton | Doug Corbett | Mark Clear | | 22 | 12 | 10 |
| 1980-04-15 | vs MIN | 5 | W 3-1 | 3-2 | 5 | 26,105 | Frank Tanana | Jerry Koosman | Frank Tanana | Jerry Koosman | | 25 | 13 | 12 |
| 1980-04-16 | vs MIN | 6 | W 2-1 | 4-2 | 3 | 27,575 | Dave Frost | Pete Redfern | Dave Frost | Mike Marshall | | 27 | 14 | 13 |
| 1980-04-18 | @ OAK | 7 | L 3-6 | 4-3 | 5 | 6,570 | Bruce Kison | Brian Kingman | Brian Kingman | Bruce Kison | | 30 | 20 | 10 |
| 1980-04-19 | @ OAK | 8 | L 1-3 | 4-4 | 5 | 5,239 | Don Aase | Mike Norris | Mike Norris | Don Aase | Jeff Jones | 31 | 23 | 8 |
| 1980-04-20 | @ OAK | 9 | L 1-6 | 4-6 | 7 | 0 | Chris Knapp | Matt Keough | Matt Keough | Chris Knapp | | 32 | 29 | 3 |
| 1980-04-20 | @ OAK | 10 | L 2-8 | 4-6 | 7 | 9,014 | Frank Tanana | Steve McCatty | Steve McCatty | Frank Tanana | | 34 | 37 | -3 |
| 1980-04-22 | @ MIN | 11 | L 1-8 | 4-7 | 7 | 36,268 | Dave Frost | Geoff Zahn | Geoff Zahn | Dave Frost | | 35 | 45 | -10 |
| 1980-04-23 | @ MIN | 12 | W 17-0 | 5-7 | 7 | 4,772 | Bruce Kison | Terry Felton | Bruce Kison | Terry Felton | | 52 | 45 | 7 |
| 1980-04-25 | @ SEA | 13 | W 4-3 | 6-7 | 7 | 9,083 | Don Aase | Mike Parrott | Don Aase | Mike Parrott | John Montague | 56 | 48 | 8 |
| 1980-04-26 | @ SEA | 14 | W 7-6 | 7-7 | 6 | 20,152 | Chris Knapp | Jim Beattie | Dave LaRoche | Rob Dressler | Mark Clear | 63 | 54 | 9 |
| 1980-04-27 | @ SEA | 15 | L 3-7 | 7-8 | 7 | 6,109 | Dave Frost | Glenn Abbott | Glenn Abbott | Dave Frost | | 66 | 61 | 5 |
| 1980-04-28 | vs OAK | 16 | L 0-8 | 7-9 | 7 | 30,889 | Bruce Kison | Rick Langford | Rick Langford | Bruce Kison | | 66 | 69 | -3 |
| 1980-04-29 | vs OAK | 17 | L 2-4 | 7-10 | 7 | 32,334 | Frank Tanana | Mike Norris | Mike Norris | Frank Tanana | | 68 | 73 | -5 |
| 1980-04-30 | vs OAK | 18 | W 2-1 | 8-10 | 7 | 22,551 | Don Aase | Matt Keough | Don Aase | Matt Keough | | 70 | 74 | -4 |
| 1980-05-01 | vs SEA | 19 | W 2-1 | 9-10 | 7 | 22,260 | Chris Knapp | Jim Beattie | John Montague | Jim Beattie | | 72 | 75 | -3 |
| 1980-05-02 | vs SEA | 20 | W 3-1 | 10-10 | 5 | 29,674 | Dave Frost | Glenn Abbott | Dave Frost | Glenn Abbott | | 75 | 76 | -1 |
| 1980-05-03 | vs SEA | 21 | L 0-2 | 10-11 | 6 | 40,376 | Bruce Kison | Rick Honeycutt | Rick Honeycutt | Bruce Kison | | 75 | 78 | -3 |
| 1980-05-04 | vs SEA | 22 | W 4-3 | 11-11 | 5 | 27,584 | Frank Tanana | Floyd Bannister | Frank Tanana | Floyd Bannister | Mark Clear | 79 | 81 | -2 |
| 1980-05-06 | vs TOR | 23 | L 2-3 | 11-12 | 5 | 23,804 | Don Aase | Dave Lemanczyk | Dave Lemanczyk | Don Aase | Jerry Garvin | 81 | 84 | -3 |
| 1980-05-07 | vs TOR | 24 | L 3-7 | 11-13 | 6 | 21,733 | Chris Knapp | Dave Stieb | Dave Stieb | Chris Knapp | | 84 | 91 | -7 |
| 1980-05-08 | vs TOR | 25 | L 2-9 | 11-14 | 6 | 23,006 | Dave Frost | Paul Mirabella | Paul Mirabella | Dave Frost | | 86 | 100 | -14 |
| 1980-05-09 | vs DET | 26 | L 5-6 | 11-15 | 6 | 27,269 | Bruce Kison | Milt Wilcox | Aurelio Lopez | John Montague | | 91 | 106 | -15 |
| 1980-05-10 | vs DET | 27 | L 1-6 | 11-16 | 7 | 35,007 | Frank Tanana | Dan Schatzeder | Dan Schatzeder | Frank Tanana | | 92 | 112 | -20 |
| 1980-05-11 | vs DET | 28 | L 0-4 | 11-17 | 7 | 31,089 | Don Aase | Dan Petry | Dan Petry | Don Aase | | 92 | 116 | -24 |
| 1980-05-14 | @ CLE | 29 | W 13-7 | 12-17 | 6 | 4,976 | Dave Frost | Dan Spillner | Chris Knapp | Dan Spillner | Jim Barr | 105 | 123 | -18 |
| 1980-05-16 | @ KCA | 30 | W 11-1 | 13-17 | 6 | 22,264 | Bruce Kison | Rich Gale | Bruce Kison | Rich Gale | | 116 | 124 | -8 |
| 1980-05-17 | @ KCA | 31 | L 1-2 | 13-18 | 6 | 30,326 | Don Aase | Larry Gura | Larry Gura | Mark Clear | | 117 | 126 | -9 |
| 1980-05-18 | @ KCA | 32 | L 3-5 | 13-19 | 7 | 25,382 | Frank Tanana | Renie Martin | Renie Martin | Frank Tanana | Dan Quisenberry | 120 | 131 | -11 |
| 1980-05-19 | @ TEX | 33 | W 3-2 | 14-19 | 6 | 15,833 | Dave Frost | Gaylord Perry | Mark Clear | Jim Kern | | 123 | 133 | -10 |
| 1980-05-20 | @ TEX | 34 | W 5-4 | 15-19 | 6 | 16,803 | Alfredo Martinez | Doc Medich | Alfredo Martinez | Doc Medich | Dave LaRoche | 128 | 137 | -9 |
| 1980-05-21 | @ TEX | 35 | W 9-8 | 16-19 | 6 | 16,232 | Bruce Kison | Steve Comer | Mark Clear | Jim Kern | | 137 | 145 | -8 |
| 1980-05-22 | @ TEX | 36 | L 6-12 | 16-20 | 6 | 15,308 | Don Aase | Jon Matlack | Danny Darwin | Don Aase | | 143 | 157 | -14 |
| 1980-05-23 | vs KCA | 37 | L 9-13 | 16-21 | 6 | 26,270 | Frank Tanana | Dennis Leonard | Dennis Leonard | Frank Tanana | | 152 | 170 | -18 |
| 1980-05-24 | vs KCA | 38 | L 5-6 | 16-22 | 6 | 34,938 | Alfredo Martinez | Rich Gale | Dan Quisenberry | Mark Clear | | 157 | 176 | -19 |
| 1980-05-25 | vs KCA | 39 | L 3-7 | 16-23 | 6 | 30,325 | Dave LaRoche | Larry Gura | Larry Gura | Dave LaRoche | | 160 | 183 | -23 |
| 1980-05-26 | vs TEX | 40 | L 5-6 | 16-24 | 6 | 34,708 | Bruce Kison | Danny Darwin | Adrian Devine | Mark Clear | Sparky Lyle | 165 | 189 | -24 |
| 1980-05-27 | vs TEX | 41 | W 2-0 | 17-24 | 6 | 22,935 | Don Aase | Fergie Jenkins | Don Aase | Fergie Jenkins | | 167 | 189 | -22 |
| 1980-05-28 | vs TEX | 42 | W 7-6 | 18-24 | 6 | 24,531 | Alfredo Martinez | Jon Matlack | Mark Clear | Jim Kern | Chris Knapp | 174 | 195 | -21 |
| 1980-05-30 | @ DET | 43 | L 1-12 | 18-25 | 6 | 22,163 | Frank Tanana | Milt Wilcox | Milt Wilcox | Frank Tanana | | 175 | 207 | -32 |
| 1980-05-31 | @ DET | 44 | W 6-1 | 19-25 | 6 | 23,350 | Bruce Kison | Pat Underwood | Bruce Kison | Pat Underwood | Dave LaRoche | 181 | 208 | -27 |
| 1980-06-02 | @ TOR | 45 | W 6-3 | 20-25 | 6 | 15,079 | Dave Frost | Luis Leal | Dave Frost | Luis Leal | Dave LaRoche | 187 | 211 | -24 |
| 1980-06-03 | @ TOR | 46 | L 6-7 | 20-26 | 6 | 15,589 | Don Aase | Dave Stieb | Joey McLaughlin | Dave LaRoche | | 193 | 218 | -25 |
| 1980-06-04 | @ TOR | 47 | L 2-8 | 20-27 | 6 | 16,677 | Alfredo Martinez | Jim Clancy | Jim Clancy | Alfredo Martinez | | 195 | 226 | -31 |
| 1980-06-06 | vs BAL | 48 | L 1-6 | 20-28 | 6 | 28,985 | Bruce Kison | Scott McGregor | Scott McGregor | Bruce Kison | | 196 | 232 | -36 |
| 1980-06-07 | vs BAL | 49 | L 5-6 | 20-29 | 7 | 37,266 | Dave Frost | Jim Palmer | Jim Palmer | Dave Frost | Tim Stoddard | 201 | 238 | -37 |
| 1980-06-08 | vs BAL | 50 | L 8-13 | 20-30 | 7 | 34,163 | Don Aase | Steve Stone | Sammy Stewart | Chris Knapp | | 209 | 251 | -42 |
| 1980-06-09 | vs NYA | 51 | L 7-8 | 20-31 | 7 | 30,126 | Alfredo Martinez | Mike Griffin | Rich Gossage | Dave Lemanczyk | | 216 | 259 | -43 |
| 1980-06-10 | vs NYA | 52 | W 5-4 | 21-31 | 7 | 38,996 | Frank Tanana | Luis Tiant | Mark Clear | Rudy May | | 221 | 263 | -42 |
| 1980-06-11 | vs NYA | 53 | L 7-9 | 21-32 | 7 | 39,593 | Bruce Kison | Tommy John | Rich Gossage | Mark Clear | | 228 | 272 | -44 |
| 1980-06-12 | vs BOS | 54 | L 2-13 | 21-33 | 7 | 27,960 | Dave Frost | Mike Torrez | Mike Torrez | Dave Frost | | 230 | 285 | -55 |
| 1980-06-13 | vs BOS | 55 | L 0-3 | 21-34 | 7 | 32,161 | Don Aase | Dennis Eckersley | Dennis Eckersley | Don Aase | Dick Drago | 230 | 288 | -58 |
| 1980-06-14 | vs BOS | 56 | L 3-7 | 21-35 | 7 | 32,133 | Alfredo Martinez | Bob Stanley | Bob Stanley | Alfredo Martinez | Tom Burgmeier | 233 | 295 | -62 |
| 1980-06-15 | vs BOS | 57 | L 5-6 | 21-36 | 7 | 40,261 | Frank Tanana | Steve Renko | Steve Renko | Frank Tanana | Skip Lockwood | 238 | 301 | -63 |
| 1980-06-16 | @ BAL | 58 | L 2-5 | 21-37 | 7 | 18,683 | Chris Knapp | Jim Palmer | Jim Palmer | Chris Knapp | Tim Stoddard | 240 | 306 | -66 |
| 1980-06-17 | @ BAL | 59 | L 3-5 | 21-38 | 7 | 17,549 | Dave Frost | Steve Stone | Steve Stone | Dave Frost | | 243 | 311 | -68 |
| 1980-06-18 | @ NYA | 60 | L 0-5 | 21-39 | 7 | 30,876 | Don Aase | Ron Guidry | Ron Guidry | Don Aase | | 243 | 316 | -73 |
| 1980-06-19 | @ NYA | 61 | L 5-7 | 21-40 | 7 | 24,143 | Alfredo Martinez | Ed Figueroa | Rudy May | Dave Lemanczyk | | 248 | 323 | -75 |
| 1980-06-20 | @ BOS | 62 | W 20-2 | 22-40 | 7 | 28,780 | Frank Tanana | Steve Renko | Frank Tanana | Steve Renko | | 268 | 325 | -57 |
| 1980-06-21 | @ BOS | 63 | W 4-2 | 23-40 | 7 | 33,442 | Chris Knapp | Chuck Rainey | Chris Knapp | Chuck Rainey | Andy Hassler | 272 | 327 | -55 |
| 1980-06-22 | @ BOS | 64 | L 3-6 | 23-41 | 7 | 30,938 | Jim Barr | Mike Torrez | Mike Torrez | Jim Barr | Tom Burgmeier | 275 | 333 | -58 |
| 1980-06-24 | vs CHA | 65 | L 1-2 | 23-42 | 7 | 25,142 | Don Aase | Britt Burns | Britt Burns | Don Aase | Ed Farmer | 276 | 335 | -59 |
| 1980-06-25 | vs CHA | 66 | L 2-5 | 23-43 | 7 | 25,372 | Dave Frost | Richard Dotson | Richard Dotson | Dave Lemanczyk | Ed Farmer | 278 | 340 | -62 |
| 1980-06-26 | vs CHA | 67 | L 2-5 | 23-44 | 7 | 24,755 | Frank Tanana | Steve Trout | Steve Trout | Frank Tanana | Mike Proly | 280 | 345 | -65 |
| 1980-06-27 | vs MIL | 68 | W 6-5 | 24-44 | 7 | 27,389 | Chris Knapp | Lary Sorensen | Mark Clear | Bill Castro | | 286 | 350 | -64 |
| 1980-06-28 | vs MIL | 69 | L 5-11 | 24-45 | 7 | 40,528 | Ed Halicki | Mike Caldwell | Mike Caldwell | Ed Halicki | | 291 | 361 | -70 |
| 1980-06-29 | vs MIL | 70 | L 2-5 | 24-46 | 7 | 27,838 | Don Aase | Reggie Cleveland | Reggie Cleveland | Don Aase | | 293 | 366 | -73 |
| 1980-06-30 | @ CHA | 71 | W 10-6 | 25-46 | 7 | 17,678 | Chris Knapp | Richard Dotson | Mark Clear | Ed Farmer | | 303 | 372 | -69 |
| 1980-07-01 | @ CHA | 72 | W 5-2 | 26-46 | 7 | 17,116 | Ed Halicki | Steve Trout | Ed Halicki | Steve Trout | Mark Clear | 308 | 374 | -66 |
| 1980-07-02 | @ CHA | 73 | L 0-1 | 26-47 | 7 | 11,653 | Frank Tanana | Ross Baumgarten | Ross Baumgarten | Frank Tanana | | 308 | 375 | -67 |
| 1980-07-03 | @ CHA | 74 | W 7-3 | 27-47 | 7 | 32,506 | Dave Lemanczyk | Rich Wortham | Dave Lemanczyk | Rich Wortham | Mark Clear | 315 | 378 | -63 |
| 1980-07-04 | @ MIL | 75 | W 2-0 | 28-47 | 7 | 21,198 | Don Aase | Reggie Cleveland | Don Aase | Reggie Cleveland | Mark Clear | 317 | 378 | -61 |
| 1980-07-05 | @ MIL | 76 | L 3-4 | 28-48 | 7 | 34,524 | Chris Knapp | Bill Travers | Bill Travers | Chris Knapp | John Flinn | 320 | 382 | -62 |
| 1980-07-06 | @ MIL | 77 | W 2-0 | 29-48 | 7 | 34,200 | Ed Halicki | Moose Haas | Ed Halicki | Moose Haas | Mark Clear | 322 | 382 | -60 |
| 1980-07-10 | @ OAK | 78 | W 5-1 | 30-49 | 7 | 0 | Frank Tanana | Matt Keough | Frank Tanana | Matt Keough | | 327 | 383 | -56 |
| 1980-07-10 | @ OAK | 79 | L 4-5 | 30-49 | 7 | 11,337 | Don Aase | Rick Langford | Rick Langford | Don Aase | | 331 | 388 | -57 |
| 1980-07-11 | @ OAK | 80 | L 2-6 | 30-50 | 7 | 7,696 | Chris Knapp | Brian Kingman | Brian Kingman | Chris Knapp | Jeff Jones | 333 | 394 | -61 |
| 1980-07-12 | vs OAK | 81 | L 4-5 | 30-51 | 7 | 32,186 | Dave Lemanczyk | Mike Norris | Mike Norris | Dave Lemanczyk | Craig Minetto | 337 | 399 | -62 |
| 1980-07-13 | vs OAK | 82 | W 5-4 | 31-51 | 7 | 24,393 | Ed Halicki | Steve McCatty | John Montague | Dave Hamilton | | 342 | 403 | -61 |
| 1980-07-14 | vs OAK | 83 | L 4-6 | 31-52 | 7 | 31,375 | Bruce Kison | Rick Langford | Rick Langford | Bruce Kison | | 346 | 409 | -63 |
| 1980-07-15 | vs CLE | 84 | W 7-1 | 32-52 | 7 | 22,951 | Frank Tanana | John Denny | Frank Tanana | John Denny | | 353 | 410 | -57 |
| 1980-07-16 | vs CLE | 85 | L 2-6 | 32-53 | 7 | 23,414 | Don Aase | Wayne Garland | Wayne Garland | Don Aase | | 355 | 416 | -61 |
| 1980-07-17 | vs CLE | 86 | L 3-5 | 32-54 | 7 | 22,796 | Chris Knapp | Len Barker | Len Barker | Chris Knapp | | 358 | 421 | -63 |
| 1980-07-18 | vs TOR | 87 | W 6-3 | 33-54 | 7 | 23,866 | Ed Halicki | Jack Kucek | Ed Halicki | Jack Kucek | Mark Clear | 364 | 424 | -60 |
| 1980-07-19 | vs TOR | 88 | L 4-5 | 33-55 | 7 | 35,221 | Alfredo Martinez | Jim Clancy | Jim Clancy | John Montague | | 368 | 429 | -61 |
| 1980-07-20 | vs TOR | 89 | L 3-6 | 33-56 | 7 | 23,903 | Frank Tanana | Balor Moore | Joey McLaughlin | Mark Clear | | 371 | 435 | -64 |
| 1980-07-21 | vs DET | 90 | L 3-14 | 33-57 | 7 | 24,594 | Don Aase | Milt Wilcox | Milt Wilcox | Don Aase | Pat Underwood | 374 | 449 | -75 |
| 1980-07-22 | vs DET | 91 | W 6-4 | 34-57 | 7 | 24,137 | Chris Knapp | Jack Morris | Andy Hassler | Dave Rozema | Mark Clear | 380 | 453 | -73 |
| 1980-07-23 | vs DET | 92 | L 6-7 | 34-58 | 7 | 26,648 | Dave LaRoche | Dan Petry | Aurelio Lopez | Mark Clear | | 386 | 460 | -74 |
| 1980-07-25 | @ CLE | 93 | L 8-9 | 34-60 | 7 | 0 | Frank Tanana | Rick Waits | Sandy Wihtol | Mark Clear | | 394 | 469 | -75 |
| 1980-07-25 | @ CLE | 94 | L 2-10 | 34-60 | 7 | 23,791 | Alfredo Martinez | Ross Grimsley | Ross Grimsley | Alfredo Martinez | Sid Monge | 396 | 479 | -83 |
| 1980-07-26 | @ CLE | 95 | L 4-14 | 34-61 | 7 | 17,624 | Don Aase | Wayne Garland | Wayne Garland | Don Aase | Victor Cruz | 400 | 493 | -93 |
| 1980-07-28 | @ DET | 96 | W 3-2 | 35-61 | 7 | 25,804 | Dave LaRoche | Dan Petry | John Montague | Dan Petry | Andy Hassler | 403 | 495 | -92 |
| 1980-07-29 | @ DET | 97 | W 7-0 | 36-61 | 7 | 23,020 | Alfredo Martinez | Bruce Robbins | Alfredo Martinez | Bruce Robbins | | 410 | 495 | -85 |
| 1980-07-30 | @ DET | 98 | W 6-5 | 37-61 | 7 | 21,907 | Frank Tanana | Dan Schatzeder | Mark Clear | Dan Schatzeder | Andy Hassler | 416 | 500 | -84 |
| 1980-07-31 | @ DET | 99 | L 6-15 | 37-62 | 7 | 19,850 | Don Aase | Milt Wilcox | Milt Wilcox | Don Aase | Dave Rozema | 422 | 515 | -93 |
| 1980-08-01 | @ TOR | 100 | L 8-9 | 37-63 | 7 | 16,145 | Chris Knapp | Jesse Jefferson | Jerry Garvin | Mark Clear | | 430 | 524 | -94 |
| 1980-08-02 | @ TOR | 101 | W 5-4 | 38-63 | 6 | 22,051 | Dave LaRoche | Mike Barlow | Dave LaRoche | Jesse Jefferson | | 435 | 528 | -93 |
| 1980-08-03 | @ TOR | 102 | L 1-3 | 38-64 | 6 | 20,404 | Alfredo Martinez | Jim Clancy | Jim Clancy | Alfredo Martinez | Mike Barlow | 436 | 531 | -95 |
| 1980-08-04 | vs SEA | 103 | W 8-3 | 39-64 | 6 | 31,634 | Frank Tanana | Glenn Abbott | Andy Hassler | Shane Rawley | | 444 | 534 | -90 |
| 1980-08-05 | vs SEA | 104 | W 5-4 | 40-64 | 6 | 22,326 | Jim Barr | Floyd Bannister | Mark Clear | Dave Heaverlo | | 449 | 538 | -89 |
| 1980-08-06 | vs SEA | 105 | W 8-3 | 41-64 | 6 | 22,599 | Chris Knapp | Rob Dressler | John Montague | Rob Dressler | | 457 | 541 | -84 |
| 1980-08-07 | vs MIN | 106 | W 4-2 | 42-64 | 6 | 24,195 | Dave LaRoche | Fernando Arroyo | Andy Hassler | Albert Williams | | 461 | 543 | -82 |
| 1980-08-08 | vs MIN | 107 | W 9-5 | 43-64 | 6 | 25,373 | Alfredo Martinez | Darrell Jackson | Dave Lemanczyk | Darrell Jackson | John Montague | 470 | 548 | -78 |
| 1980-08-09 | vs MIN | 108 | W 8-2 | 44-64 | 6 | 32,560 | Frank Tanana | Geoff Zahn | Frank Tanana | Geoff Zahn | | 478 | 550 | -72 |
| 1980-08-10 | vs MIN | 109 | L 2-5 | 44-65 | 6 | 23,007 | Jim Barr | Jerry Koosman | Jerry Koosman | Jim Barr | Doug Corbett | 480 | 555 | -75 |
| 1980-08-12 | @ SEA | 110 | W 9-6 | 45-65 | 6 | 16,313 | Chris Knapp | Rob Dressler | Mark Clear | Dave Heaverlo | | 489 | 561 | -72 |
| 1980-08-13 | @ SEA | 111 | W 10-4 | 46-65 | 6 | 9,369 | Dave LaRoche | Jim Beattie | Andy Hassler | Shane Rawley | | 499 | 565 | -66 |
| 1980-08-14 | @ SEA | 112 | W 2-1 | 47-65 | 6 | 7,326 | Alfredo Martinez | Rick Honeycutt | Alfredo Martinez | Rick Honeycutt | Don Aase | 501 | 566 | -65 |
| 1980-08-15 | @ MIN | 113 | W 5-4 | 48-65 | 6 | 14,685 | Frank Tanana | Geoff Zahn | Frank Tanana | Geoff Zahn | Andy Hassler | 506 | 570 | -64 |
| 1980-08-17 | @ MIN | 114 | L 1-8 | 48-67 | 6 | 0 | Jim Barr | Roger Erickson | Roger Erickson | Jim Barr | | 507 | 578 | -71 |
| 1980-08-17 | @ MIN | 115 | L 5-6 | 48-67 | 6 | 16,400 | Chris Knapp | Jerry Koosman | Jerry Koosman | Chris Knapp | Doug Corbett | 512 | 584 | -72 |
| 1980-08-18 | @ MIN | 116 | L 3-8 | 48-68 | 6 | 2,508 | Dave LaRoche | Fernando Arroyo | Fernando Arroyo | Dave LaRoche | | 515 | 592 | -77 |
| 1980-08-19 | vs BAL | 117 | L 2-5 | 48-69 | 6 | 34,116 | Alfredo Martinez | Steve Stone | Steve Stone | Alfredo Martinez | Tippy Martinez | 517 | 597 | -80 |
| 1980-08-20 | vs BAL | 118 | L 5-6 | 48-70 | 6 | 27,013 | Frank Tanana | Mike Flanagan | Tim Stoddard | Mark Clear | | 522 | 603 | -81 |
| 1980-08-21 | vs BAL | 119 | L 1-7 | 48-71 | 6 | 26,189 | Chris Knapp | Scott McGregor | Scott McGregor | Chris Knapp | | 523 | 610 | -87 |
| 1980-08-22 | vs NYA | 120 | W 8-4 | 49-71 | 6 | 40,372 | Jim Barr | Luis Tiant | Don Aase | Luis Tiant | Andy Hassler | 531 | 614 | -83 |
| 1980-08-23 | vs NYA | 121 | L 2-5 | 49-72 | 6 | 38,331 | Dave LaRoche | Rudy May | Rudy May | Dave LaRoche | Rich Gossage | 533 | 619 | -86 |
| 1980-08-24 | vs NYA | 122 | L 2-4 | 49-73 | 6 | 38,606 | Alfredo Martinez | Tom Underwood | Ron Davis | Alfredo Martinez | Rich Gossage | 535 | 623 | -88 |
| 1980-08-25 | vs BOS | 123 | L 2-4 | 49-74 | 6 | 25,653 | Frank Tanana | Dennis Eckersley | Bob Stanley | Mark Clear | | 537 | 627 | -90 |
| 1980-08-26 | vs BOS | 124 | L 1-5 | 49-75 | 6 | 29,007 | Chris Knapp | John Tudor | John Tudor | Chris Knapp | Bob Stanley | 538 | 632 | -94 |
| 1980-08-28 | @ BAL | 125 | L 8-13 | 49-76 | 6 | 30,968 | Dave LaRoche | Jim Palmer | Jim Palmer | Dave LaRoche | | 546 | 645 | -99 |
| 1980-08-29 | @ BAL | 126 | W 5-0 | 50-76 | 6 | 33,542 | Alfredo Martinez | Steve Stone | Alfredo Martinez | Steve Stone | | 551 | 645 | -94 |
| 1980-08-30 | @ BAL | 127 | W 12-6 | 51-76 | 6 | 38,234 | Frank Tanana | Mike Flanagan | Mark Clear | Mike Flanagan | | 563 | 651 | -88 |
| 1980-08-31 | @ BAL | 128 | L 0-5 | 51-77 | 6 | 23,746 | Chris Knapp | Scott McGregor | Scott McGregor | Chris Knapp | | 563 | 656 | -93 |
| 1980-09-01 | @ BOS | 129 | L 3-4 | 51-78 | 6 | 23,877 | Dave Frost | Dick Drago | Dick Drago | Dave Frost | Tom Burgmeier | 566 | 660 | -94 |
| 1980-09-02 | @ BOS | 130 | L 2-10 | 51-79 | 6 | 19,693 | Jim Dorsey | Steve Renko | Steve Renko | Jim Dorsey | | 568 | 670 | -102 |
| 1980-09-03 | @ BOS | 131 | W 7-2 | 52-79 | 6 | 22,340 | Alfredo Martinez | Mike Torrez | Alfredo Martinez | Mike Torrez | | 575 | 672 | -97 |
| 1980-09-04 | @ NYA | 132 | L 3-5 | 52-80 | 6 | 20,967 | Frank Tanana | Gaylord Perry | Gaylord Perry | Frank Tanana | Ron Guidry | 578 | 677 | -99 |
| 1980-09-05 | @ NYA | 133 | L 5-6 | 52-81 | 6 | 30,109 | Ralph Botting | Luis Tiant | Rich Gossage | Andy Hassler | | 583 | 683 | -100 |
| 1980-09-06 | @ NYA | 134 | L 4-7 | 52-82 | 6 | 37,781 | Dave Frost | Tom Underwood | Tom Underwood | Dave Frost | Rich Gossage | 587 | 690 | -103 |
| 1980-09-07 | @ NYA | 135 | L 1-4 | 52-83 | 6 | 38,794 | Jim Dorsey | Rudy May | Rudy May | Jim Dorsey | Rich Gossage | 588 | 694 | -106 |
| 1980-09-08 | vs KCA | 136 | W 7-4 | 53-83 | 6 | 23,050 | Alfredo Martinez | Larry Gura | Don Aase | Larry Gura | Andy Hassler | 595 | 698 | -103 |
| 1980-09-09 | vs KCA | 137 | W 4-3 | 54-83 | 6 | 24,131 | Frank Tanana | Paul Splittorff | Frank Tanana | Paul Splittorff | Mark Clear | 599 | 701 | -102 |
| 1980-09-10 | vs KCA | 138 | W 8-3 | 55-83 | 6 | 24,762 | Ralph Botting | Renie Martin | Don Aase | Renie Martin | Andy Hassler | 607 | 704 | -97 |
| 1980-09-11 | vs KCA | 139 | L 2-7 | 55-84 | 6 | 22,844 | Bob Ferris | Dennis Leonard | Dennis Leonard | Bob Ferris | | 609 | 711 | -102 |
| 1980-09-12 | vs TEX | 140 | W 8-4 | 56-84 | 6 | 23,006 | Jim Dorsey | Doc Medich | Jim Dorsey | Doc Medich | Dave LaRoche | 617 | 715 | -98 |
| 1980-09-13 | vs TEX | 141 | W 10-1 | 57-84 | 6 | 26,060 | Alfredo Martinez | John Butcher | Alfredo Martinez | John Butcher | | 627 | 716 | -89 |
| 1980-09-14 | vs TEX | 142 | W 3-1 | 58-84 | 6 | 28,561 | Frank Tanana | Ken Clay | Frank Tanana | Ken Clay | Andy Hassler | 630 | 717 | -87 |
| 1980-09-17 | @ KCA | 143 | L 0-5 | 59-85 | 6 | 0 | Ralph Botting | Dennis Leonard | Dennis Leonard | Ralph Botting | | 630 | 722 | -92 |
| 1980-09-17 | @ KCA | 144 | W 7-4 | 59-85 | 6 | 25,908 | Bob Ferris | Larry Gura | Dave LaRoche | Larry Gura | Andy Hassler | 637 | 726 | -89 |
| 1980-09-18 | @ KCA | 145 | L 2-5 | 59-86 | 6 | 19,559 | Alfredo Martinez | Renie Martin | Renie Martin | Alfredo Martinez | | 639 | 731 | -92 |
| 1980-09-19 | @ TEX | 146 | W 6-2 | 60-86 | 6 | 9,024 | Frank Tanana | Jon Matlack | Frank Tanana | Jon Matlack | | 645 | 733 | -88 |
| 1980-09-20 | @ TEX | 147 | W 6-4 | 61-86 | 6 | 10,938 | Jim Dorsey | Don Kainer | Andy Hassler | Charlie Hough | | 651 | 737 | -86 |
| 1980-09-21 | @ TEX | 148 | W 9-2 | 62-86 | 6 | 6,794 | Jim Barr | Doc Medich | Jim Barr | Doc Medich | Don Aase | 660 | 739 | -79 |
| 1980-09-22 | @ MIL | 149 | W 7-3 | 63-86 | 6 | 5,301 | Ralph Botting | Moose Haas | Mark Clear | Bob McClure | | 667 | 742 | -75 |
| 1980-09-23 | @ MIL | 150 | W 2-1 | 64-86 | 5 | 6,195 | Alfredo Martinez | Mike Caldwell | Alfredo Martinez | Mike Caldwell | Andy Hassler | 669 | 743 | -74 |
| 1980-09-24 | @ MIL | 151 | L 0-6 | 64-87 | 5 | 5,974 | Frank Tanana | Lary Sorensen | Lary Sorensen | Frank Tanana | | 669 | 749 | -80 |
| 1980-09-26 | vs CHA | 152 | L 4-5 | 64-88 | 6 | 22,578 | Jim Barr | LaMarr Hoyt | Dewey Robinson | Jim Barr | Ed Farmer | 673 | 754 | -81 |
| 1980-09-27 | vs CHA | 153 | L 3-6 | 64-89 | 6 | 20,398 | Ralph Botting | Richard Dotson | Richard Dotson | Ralph Botting | | 676 | 760 | -84 |
| 1980-09-28 | vs CHA | 154 | L 1-8 | 64-90 | 6 | 29,012 | Alfredo Martinez | Britt Burns | Britt Burns | Alfredo Martinez | | 677 | 768 | -91 |
| 1980-09-29 | vs MIL | 155 | W 6-2 | 65-90 | 6 | 19,869 | Frank Tanana | Lary Sorensen | Frank Tanana | Lary Sorensen | | 683 | 770 | -87 |
| 1980-09-30 | vs MIL | 156 | L 2-4 | 65-91 | 6 | 20,059 | Bob Ferris | Bob McClure | Bob McClure | Bob Ferris | Mike Caldwell | 685 | 774 | -89 |
| 1980-10-01 | vs MIL | 157 | L 7-10 | 65-92 | 6 | 20,891 | Ed Halicki | Dave LaPoint | Bill Castro | Dave Schuler | Lary Sorensen | 692 | 784 | -92 |
| 1980-10-03 | @ CHA | 158 | L 1-4 | 65-93 | 6 | 6,722 | Alfredo Martinez | Britt Burns | Britt Burns | Alfredo Martinez | Mike Proly | 693 | 788 | -95 |
| 1980-10-04 | @ CHA | 159 | L 2-4 | 65-94 | 6 | 7,788 | Frank Tanana | LaMarr Hoyt | LaMarr Hoyt | Frank Tanana | Ed Farmer | 695 | 792 | -97 |
| 1980-10-05 | @ CHA | 160 | L 3-5 | 65-95 | 6 | 8,795 | Ralph Botting | Steve Trout | Steve Trout | Ralph Botting | Mike Proly | 698 | 797 | -99 |