| 1980-04-11 | @ CAL | 1 | L 2-10 | 0-1 | 6 | 37,085 | Dan Spillner | Dave Frost | Dave Frost | Dan Spillner | | 2 | 10 | -8 |
| 1980-04-12 | @ CAL | 2 | W 2-1 | 1-1 | 2 | 32,353 | Len Barker | Bruce Kison | Len Barker | Bruce Kison | Sid Monge | 4 | 11 | -7 |
| 1980-04-13 | @ CAL | 3 | L 3-8 | 1-2 | 4 | 33,628 | John Denny | Don Aase | Don Aase | John Denny | John Montague | 7 | 19 | -12 |
| 1980-04-14 | @ TEX | 4 | L 4-7 | 1-3 | 5 | 8,656 | Rick Waits | Doc Medich | Doc Medich | Rick Waits | Sparky Lyle | 11 | 26 | -15 |
| 1980-04-15 | @ TEX | 5 | L 0-3 | 1-4 | 6 | 11,895 | Bob Owchinko | Jon Matlack | Jon Matlack | Bob Owchinko | | 11 | 29 | -18 |
| 1980-04-16 | @ TEX | 6 | L 7-8 | 1-5 | 6 | 11,557 | Len Barker | Fergie Jenkins | Jim Kern | Victor Cruz | | 18 | 37 | -19 |
| 1980-04-19 | vs TOR | 7 | W 8-1 | 2-5 | 6 | 61,753 | Rick Waits | Jim Clancy | Rick Waits | Jim Clancy | | 26 | 38 | -12 |
| 1980-04-20 | vs TOR | 8 | L 3-5 | 2-6 | 6 | 11,220 | John Denny | Dave Lemanczyk | Dave Lemanczyk | John Denny | Joey McLaughlin | 29 | 43 | -14 |
| 1980-04-21 | @ MIL | 9 | L 5-7 | 2-7 | 6 | 10,414 | Bob Owchinko | Lary Sorensen | Bob McClure | Victor Cruz | | 34 | 50 | -16 |
| 1980-04-22 | @ MIL | 10 | L 4-8 | 2-8 | 7 | 15,898 | Len Barker | Mike Caldwell | Mike Caldwell | Len Barker | | 38 | 58 | -20 |
| 1980-04-23 | @ MIL | 11 | W 7-3 | 3-8 | 7 | 9,053 | Dan Spillner | Moose Haas | Dan Spillner | Moose Haas | | 45 | 61 | -16 |
| 1980-04-25 | vs TEX | 12 | L 1-4 | 3-9 | 7 | 7,126 | Rick Waits | Gaylord Perry | Danny Darwin | Rick Waits | | 46 | 65 | -19 |
| 1980-04-26 | vs TEX | 13 | W 8-7 | 4-9 | 7 | 7,092 | John Denny | Jon Matlack | Victor Cruz | Jim Kern | Mike Stanton | 54 | 72 | -18 |
| 1980-04-27 | vs TEX | 14 | W 7-4 | 5-9 | 7 | 12,879 | Len Barker | Fergie Jenkins | Len Barker | Fergie Jenkins | | 61 | 76 | -15 |
| 1980-04-29 | vs MIL | 15 | L 1-14 | 5-10 | 7 | 4,008 | Bob Owchinko | Bill Travers | Bill Travers | Bob Owchinko | | 62 | 90 | -28 |
| 1980-05-01 | @ TOR | 16 | W 2-1 | 6-10 | 7 | 11,654 | John Denny | Dave Lemanczyk | John Denny | Dave Lemanczyk | Sid Monge | 64 | 91 | -27 |
| 1980-05-02 | @ TOR | 17 | W 6-1 | 7-10 | 6 | 14,292 | Len Barker | Dave Stieb | Len Barker | Dave Stieb | | 70 | 92 | -22 |
| 1980-05-03 | @ TOR | 18 | L 3-8 | 7-11 | 6 | 16,564 | Rick Waits | Paul Mirabella | Tom Buskey | Rick Waits | | 73 | 100 | -27 |
| 1980-05-04 | @ TOR | 19 | L 8-9 | 7-13 | 7 | 0 | Dan Spillner | Jim Clancy | Tom Buskey | Sid Monge | | 81 | 109 | -28 |
| 1980-05-04 | @ TOR | 20 | L 2-7 | 7-13 | 7 | 26,114 | Bob Owchinko | Jesse Jefferson | Jesse Jefferson | Bob Owchinko | Joey McLaughlin | 83 | 116 | -33 |
| 1980-05-05 | @ OAK | 21 | L 1-5 | 7-14 | 7 | 12,605 | John Denny | Matt Keough | Matt Keough | John Denny | | 84 | 121 | -37 |
| 1980-05-06 | @ OAK | 22 | W 4-3 | 8-14 | 7 | 24,309 | Len Barker | Steve McCatty | Len Barker | Steve McCatty | | 88 | 124 | -36 |
| 1980-05-07 | @ OAK | 23 | W 2-1 | 9-14 | 6 | 4,731 | Rick Waits | Brian Kingman | Rick Waits | Brian Kingman | | 90 | 125 | -35 |
| 1980-05-09 | @ SEA | 24 | W 4-1 | 10-14 | 6 | 23,229 | Dan Spillner | Floyd Bannister | Dan Spillner | Floyd Bannister | | 94 | 126 | -32 |
| 1980-05-10 | @ SEA | 25 | W 5-3 | 11-14 | 6 | 10,690 | John Denny | Byron McLaughlin | John Denny | Byron McLaughlin | Victor Cruz | 99 | 129 | -30 |
| 1980-05-11 | @ SEA | 26 | L 4-9 | 11-15 | 7 | 6,683 | Len Barker | Jim Beattie | Jim Beattie | Len Barker | | 103 | 138 | -35 |
| 1980-05-14 | vs CAL | 27 | L 7-13 | 11-16 | 7 | 4,976 | Dan Spillner | Dave Frost | Chris Knapp | Dan Spillner | Jim Barr | 110 | 151 | -41 |
| 1980-05-15 | vs BOS | 28 | L 2-6 | 11-17 | 7 | 6,700 | Rick Waits | Jack Billingham | Jack Billingham | Rick Waits | Dick Drago | 112 | 157 | -45 |
| 1980-05-16 | vs BOS | 29 | L 1-2 | 11-18 | 7 | 10,157 | John Denny | Chuck Rainey | Chuck Rainey | John Denny | Tom Burgmeier | 113 | 159 | -46 |
| 1980-05-17 | vs BOS | 30 | W 4-3 | 12-18 | 7 | 20,245 | Len Barker | Mike Torrez | Mike Stanton | Keith MacWhorter | | 117 | 162 | -45 |
| 1980-05-18 | vs BOS | 31 | W 3-1 | 13-18 | 7 | 28,724 | Dan Spillner | Bob Stanley | Dan Spillner | Bob Stanley | Sid Monge | 120 | 163 | -43 |
| 1980-05-19 | vs BAL | 32 | L 1-4 | 13-19 | 7 | 5,409 | Rick Waits | Steve Stone | Steve Stone | Rick Waits | Tim Stoddard | 121 | 167 | -46 |
| 1980-05-20 | vs BAL | 33 | W 4-0 | 14-20 | 7 | 0 | John Denny | Sammy Stewart | John Denny | Sammy Stewart | | 125 | 167 | -42 |
| 1980-05-20 | vs BAL | 34 | L 0-8 | 14-20 | 7 | 11,856 | Bob Owchinko | Jim Palmer | Jim Palmer | Bob Owchinko | | 125 | 175 | -50 |
| 1980-05-21 | vs BAL | 35 | W 4-2 | 15-20 | 7 | 6,739 | Len Barker | Mike Flanagan | Len Barker | Mike Flanagan | Sid Monge | 129 | 177 | -48 |
| 1980-05-23 | @ BOS | 36 | L 1-4 | 15-21 | 7 | 21,857 | Dan Spillner | Bob Stanley | Bob Stanley | Dan Spillner | Tom Burgmeier | 130 | 181 | -51 |
| 1980-05-24 | @ BOS | 37 | W 7-2 | 16-21 | 6 | 22,719 | Rick Waits | Jack Billingham | Rick Waits | Jack Billingham | | 137 | 183 | -46 |
| 1980-05-25 | @ BOS | 38 | W 3-2 | 17-21 | 6 | 24,391 | John Denny | Chuck Rainey | John Denny | Chuck Rainey | | 140 | 185 | -45 |
| 1980-05-26 | @ BAL | 39 | L 3-7 | 17-22 | 6 | 14,298 | Len Barker | Scott McGregor | Scott McGregor | Len Barker | Tim Stoddard | 143 | 192 | -49 |
| 1980-05-27 | @ BAL | 40 | W 7-6 | 18-22 | 6 | 10,092 | Dan Spillner | Steve Stone | Victor Cruz | Dave Ford | | 150 | 198 | -48 |
| 1980-05-28 | @ BAL | 41 | W 10-6 | 19-22 | 5 | 12,178 | Rick Waits | Jim Palmer | Rick Waits | Jim Palmer | Sid Monge | 160 | 204 | -44 |
| 1980-05-29 | vs MIL | 42 | W 5-0 | 20-22 | 5 | 6,149 | John Denny | Moose Haas | John Denny | Moose Haas | | 165 | 204 | -39 |
| 1980-05-30 | vs SEA | 43 | L 3-4 | 20-23 | 6 | 18,161 | Len Barker | Floyd Bannister | Dave Heaverlo | Sid Monge | | 168 | 208 | -40 |
| 1980-05-31 | vs SEA | 44 | W 5-2 | 21-23 | 6 | 11,107 | Dan Spillner | Mike Parrott | Dan Spillner | Mike Parrott | | 173 | 210 | -37 |
| 1980-06-01 | vs SEA | 45 | L 7-8 | 21-24 | 6 | 25,376 | Rick Waits | Jim Beattie | Dave Heaverlo | Sid Monge | | 180 | 218 | -38 |
| 1980-06-02 | vs OAK | 46 | W 10-5 | 22-24 | 6 | 4,445 | Wayne Garland | Brian Kingman | Wayne Garland | Brian Kingman | | 190 | 223 | -33 |
| 1980-06-03 | vs OAK | 47 | W 6-4 | 23-24 | 4 | 4,597 | Len Barker | Rick Langford | Victor Cruz | Rick Langford | | 196 | 227 | -31 |
| 1980-06-04 | vs OAK | 48 | W 5-3 | 24-24 | 4 | 8,608 | Dan Spillner | Steve McCatty | Dan Spillner | Steve McCatty | Victor Cruz | 201 | 230 | -29 |
| 1980-06-06 | @ CHA | 49 | L 7-8 | 24-25 | 5 | 20,231 | Rick Waits | Steve Trout | Ed Farmer | Sid Monge | | 208 | 238 | -30 |
| 1980-06-08 | @ CHA | 50 | W 7-2 | 25-25 | 4 | 31,593 | John Denny | Britt Burns | John Denny | Britt Burns | Mike Stanton | 215 | 240 | -25 |
| 1980-06-10 | vs KCA | 51 | L 4-8 | 25-26 | 6 | 6,061 | Len Barker | Renie Martin | Marty Pattin | Len Barker | | 219 | 248 | -29 |
| 1980-06-11 | vs KCA | 52 | L 0-5 | 26-27 | 5 | 0 | Rick Waits | Dennis Leonard | Dennis Leonard | Rick Waits | | 219 | 253 | -34 |
| 1980-06-11 | vs KCA | 53 | W 8-5 | 26-27 | 5 | 13,712 | Dan Spillner | Paul Splittorff | Dan Spillner | Rich Gale | | 227 | 258 | -31 |
| 1980-06-13 | vs MIN | 54 | W 6-2 | 27-27 | 4 | 11,336 | John Denny | Jerry Koosman | John Denny | Jerry Koosman | | 233 | 260 | -27 |
| 1980-06-14 | vs MIN | 55 | W 3-2 | 28-27 | 4 | 12,948 | Len Barker | Roger Erickson | Len Barker | Roger Erickson | | 236 | 262 | -26 |
| 1980-06-15 | vs MIN | 56 | W 14-5 | 29-27 | 4 | 25,182 | Dan Spillner | Darrell Jackson | Dan Spillner | Darrell Jackson | | 250 | 267 | -17 |
| 1980-06-16 | vs CHA | 57 | W 5-3 | 30-27 | 3 | 11,184 | Wayne Garland | Ross Baumgarten | Wayne Garland | Ed Farmer | | 255 | 270 | -15 |
| 1980-06-17 | vs CHA | 58 | L 3-5 | 30-28 | 4 | 9,614 | Rick Waits | Ken Kravec | LaMarr Hoyt | Victor Cruz | | 258 | 275 | -17 |
| 1980-06-18 | @ KCA | 59 | L 2-10 | 30-29 | 5 | 23,736 | John Denny | Larry Gura | Larry Gura | John Denny | | 260 | 285 | -25 |
| 1980-06-19 | @ KCA | 60 | W 5-4 | 31-29 | 5 | 21,158 | Len Barker | Renie Martin | Len Barker | Renie Martin | Mike Stanton | 265 | 289 | -24 |
| 1980-06-20 | @ MIN | 61 | W 4-3 | 32-29 | 4 | 7,668 | Dan Spillner | Roger Erickson | Victor Cruz | Pete Redfern | Mike Stanton | 269 | 292 | -23 |
| 1980-06-21 | @ MIN | 62 | L 2-3 | 32-30 | 5 | 7,665 | Wayne Garland | Geoff Zahn | Geoff Zahn | Wayne Garland | Darrell Jackson | 271 | 295 | -24 |
| 1980-06-22 | @ MIN | 63 | W 11-6 | 33-30 | 4 | 9,676 | Rick Waits | Pete Redfern | Rick Waits | Pete Redfern | | 282 | 301 | -19 |
| 1980-06-23 | vs DET | 64 | L 4-5 | 33-31 | 5 | 19,564 | Bob Owchinko | Pat Underwood | Dan Schatzeder | Mike Stanton | | 286 | 306 | -20 |
| 1980-06-24 | vs DET | 65 | L 4-9 | 33-32 | 6 | 11,692 | Len Barker | Dan Petry | Roger Weaver | Len Barker | Aurelio Lopez | 290 | 315 | -25 |
| 1980-06-25 | vs DET | 66 | L 3-13 | 33-33 | 6 | 11,873 | Dan Spillner | Milt Wilcox | Milt Wilcox | Dan Spillner | | 293 | 328 | -35 |
| 1980-06-27 | @ NYA | 67 | W 2-0 | 34-33 | 6 | 30,421 | Rick Waits | Rudy May | Rick Waits | Rudy May | | 295 | 328 | -33 |
| 1980-06-28 | @ NYA | 68 | L 10-11 | 34-34 | 6 | 42,192 | Wayne Garland | Tom Underwood | Rich Gossage | Victor Cruz | | 305 | 339 | -34 |
| 1980-06-29 | @ NYA | 69 | L 2-7 | 34-35 | 6 | 53,231 | Len Barker | Ron Guidry | Ron Guidry | Len Barker | Ron Davis | 307 | 346 | -39 |
| 1980-06-30 | @ DET | 70 | L 4-9 | 34-36 | 6 | 30,085 | Dan Spillner | Milt Wilcox | Dan Schatzeder | Dan Spillner | Aurelio Lopez | 311 | 355 | -44 |
| 1980-07-01 | @ DET | 71 | W 8-7 | 35-36 | 6 | 27,830 | John Denny | Bruce Robbins | Bob Owchinko | Pat Underwood | Mike Stanton | 319 | 362 | -43 |
| 1980-07-02 | @ DET | 72 | L 6-7 | 35-37 | 6 | 25,981 | Rick Waits | Jack Morris | Jack Morris | Rick Waits | Aurelio Lopez | 325 | 369 | -44 |
| 1980-07-03 | vs NYA | 73 | W 7-0 | 36-37 | 6 | 73,096 | Wayne Garland | Tom Underwood | Wayne Garland | Tom Underwood | | 332 | 369 | -37 |
| 1980-07-04 | vs NYA | 74 | L 5-11 | 36-38 | 6 | 21,312 | Len Barker | Ron Guidry | Ron Guidry | Len Barker | | 337 | 380 | -43 |
| 1980-07-05 | vs NYA | 75 | L 2-3 | 36-39 | 6 | 36,614 | Dan Spillner | Tommy John | Tommy John | Dan Spillner | Rich Gossage | 339 | 383 | -44 |
| 1980-07-06 | vs NYA | 76 | W 5-3 | 37-39 | 6 | 43,209 | Rick Waits | Ed Figueroa | Rick Waits | Ed Figueroa | Sid Monge | 344 | 386 | -42 |
| 1980-07-10 | @ TOR | 77 | W 7-3 | 38-39 | 6 | 17,178 | John Denny | Jim Clancy | John Denny | Jim Clancy | | 351 | 389 | -38 |
| 1980-07-11 | @ TOR | 78 | L 3-6 | 38-40 | 6 | 16,621 | Wayne Garland | Dave Stieb | Dave Stieb | Wayne Garland | | 354 | 395 | -41 |
| 1980-07-12 | @ TEX | 79 | W 9-8 | 39-40 | 6 | 27,784 | Len Barker | Gaylord Perry | Len Barker | Gaylord Perry | Victor Cruz | 363 | 403 | -40 |
| 1980-07-13 | @ TEX | 80 | L 2-12 | 39-41 | 6 | 12,503 | Dan Spillner | Doc Medich | Doc Medich | Dan Spillner | | 365 | 415 | -50 |
| 1980-07-14 | @ TEX | 81 | L 2-4 | 39-42 | 6 | 9,446 | Rick Waits | Steve Comer | Danny Darwin | Rick Waits | | 367 | 419 | -52 |
| 1980-07-15 | @ CAL | 82 | L 1-7 | 39-43 | 6 | 22,951 | John Denny | Frank Tanana | Frank Tanana | John Denny | | 368 | 426 | -58 |
| 1980-07-16 | @ CAL | 83 | W 6-2 | 40-43 | 6 | 23,414 | Wayne Garland | Don Aase | Wayne Garland | Don Aase | | 374 | 428 | -54 |
| 1980-07-17 | @ CAL | 84 | W 5-3 | 41-43 | 6 | 22,796 | Len Barker | Chris Knapp | Len Barker | Chris Knapp | | 379 | 431 | -52 |
| 1980-07-18 | @ OAK | 85 | L 1-9 | 41-44 | 6 | 5,912 | Dan Spillner | Mike Norris | Mike Norris | Dan Spillner | | 380 | 440 | -60 |
| 1980-07-19 | @ OAK | 86 | L 0-3 | 41-45 | 6 | 6,506 | Rick Waits | Steve McCatty | Steve McCatty | Rick Waits | | 380 | 443 | -63 |
| 1980-07-20 | @ OAK | 87 | L 5-6 | 41-46 | 6 | 10,606 | Ross Grimsley | Rick Langford | Rick Langford | Victor Cruz | | 385 | 449 | -64 |
| 1980-07-21 | @ SEA | 88 | L 0-7 | 41-47 | 6 | 5,050 | Wayne Garland | Glenn Abbott | Glenn Abbott | Wayne Garland | | 385 | 456 | -71 |
| 1980-07-22 | @ SEA | 89 | W 4-0 | 42-47 | 6 | 5,727 | Len Barker | Floyd Bannister | Len Barker | Floyd Bannister | | 389 | 456 | -67 |
| 1980-07-23 | @ SEA | 90 | W 12-6 | 43-47 | 6 | 6,387 | Bob Owchinko | Jim Beattie | Victor Cruz | Shane Rawley | | 401 | 462 | -61 |
| 1980-07-25 | vs CAL | 91 | W 9-8 | 45-47 | 6 | 0 | Rick Waits | Frank Tanana | Sandy Wihtol | Mark Clear | | 410 | 470 | -60 |
| 1980-07-25 | vs CAL | 92 | W 10-2 | 45-47 | 6 | 23,791 | Ross Grimsley | Alfredo Martinez | Ross Grimsley | Alfredo Martinez | Sid Monge | 420 | 472 | -52 |
| 1980-07-26 | vs CAL | 93 | W 14-4 | 46-47 | 6 | 17,624 | Wayne Garland | Don Aase | Wayne Garland | Don Aase | Victor Cruz | 434 | 476 | -42 |
| 1980-07-28 | vs SEA | 94 | W 7-3 | 47-47 | 6 | 5,712 | Len Barker | Jim Beattie | Len Barker | Jim Beattie | Victor Cruz | 441 | 479 | -38 |
| 1980-07-29 | vs SEA | 95 | W 7-2 | 48-47 | 5 | 8,600 | Dan Spillner | Rick Honeycutt | Dan Spillner | Rick Honeycutt | Sid Monge | 448 | 481 | -33 |
| 1980-07-30 | vs SEA | 96 | W 5-2 | 49-47 | 5 | 10,352 | Ross Grimsley | Glenn Abbott | Ross Grimsley | Glenn Abbott | | 453 | 483 | -30 |
| 1980-08-01 | vs OAK | 97 | L 1-2 | 49-48 | 5 | 16,439 | Rick Waits | Brian Kingman | Brian Kingman | Rick Waits | Dave Beard | 454 | 485 | -31 |
| 1980-08-03 | vs OAK | 98 | L 3-11 | 50-49 | 6 | 0 | Wayne Garland | Matt Keough | Matt Keough | Wayne Garland | Jeff Jones | 457 | 496 | -39 |
| 1980-08-03 | vs OAK | 99 | W 4-2 | 50-49 | 6 | 17,587 | Len Barker | Mike Norris | Len Barker | Mike Norris | | 461 | 498 | -37 |
| 1980-08-04 | vs TOR | 100 | W 11-5 | 51-49 | 6 | 7,583 | Dan Spillner | Paul Mirabella | Dan Spillner | Paul Mirabella | Sid Monge | 472 | 503 | -31 |
| 1980-08-05 | vs TOR | 101 | W 8-5 | 52-49 | 6 | 6,707 | Ross Grimsley | Jack Kucek | Ross Grimsley | Jack Kucek | Victor Cruz | 480 | 508 | -28 |
| 1980-08-06 | vs TOR | 102 | W 5-2 | 53-49 | 5 | 9,098 | Rick Waits | Jesse Jefferson | Rick Waits | Jesse Jefferson | Victor Cruz | 485 | 510 | -25 |
| 1980-08-07 | vs TOR | 103 | W 7-6 | 54-49 | 4 | 9,586 | Wayne Garland | Jack Kucek | Sid Monge | Jerry Garvin | | 492 | 516 | -24 |
| 1980-08-08 | @ MIL | 104 | L 1-4 | 54-50 | 6 | 27,629 | Len Barker | Bill Travers | Bill Travers | Len Barker | | 493 | 520 | -27 |
| 1980-08-09 | @ MIL | 105 | L 2-4 | 54-51 | 6 | 37,690 | Bob Owchinko | Moose Haas | Moose Haas | Bob Owchinko | | 495 | 524 | -29 |
| 1980-08-10 | @ MIL | 106 | L 1-5 | 55-52 | 6 | 0 | Ross Grimsley | Mike Caldwell | Mike Caldwell | Ross Grimsley | | 496 | 529 | -33 |
| 1980-08-10 | @ MIL | 107 | W 9-4 | 55-52 | 6 | 33,857 | Dan Spillner | Reggie Cleveland | Dan Spillner | Reggie Cleveland | | 505 | 533 | -28 |
| 1980-08-12 | vs TEX | 108 | W 2-1 | 56-52 | 6 | 9,960 | Rick Waits | Fergie Jenkins | Rick Waits | Fergie Jenkins | Victor Cruz | 507 | 534 | -27 |
| 1980-08-13 | vs TEX | 109 | W 14-3 | 57-52 | 5 | 13,449 | Wayne Garland | Doc Medich | Wayne Garland | Doc Medich | | 521 | 537 | -16 |
| 1980-08-14 | vs TEX | 110 | W 7-2 | 58-52 | 5 | 10,888 | Len Barker | Ed Figueroa | Len Barker | Ed Figueroa | | 528 | 539 | -11 |
| 1980-08-15 | vs MIL | 111 | L 1-4 | 58-53 | 6 | 16,031 | Ross Grimsley | Mike Caldwell | Mike Caldwell | Ross Grimsley | | 529 | 543 | -14 |
| 1980-08-16 | vs MIL | 112 | L 5-10 | 58-54 | 6 | 17,883 | Dan Spillner | Reggie Cleveland | Jerry Augustine | Dan Spillner | | 534 | 553 | -19 |
| 1980-08-17 | vs MIL | 113 | L 0-4 | 58-56 | 6 | 0 | Rick Waits | Paul Mitchell | Paul Mitchell | Rick Waits | | 534 | 557 | -23 |
| 1980-08-17 | vs MIL | 114 | L 1-11 | 58-56 | 6 | 23,562 | Bob Owchinko | Lary Sorensen | Lary Sorensen | Bob Owchinko | | 535 | 568 | -33 |
| 1980-08-18 | @ CHA | 115 | W 4-2 | 59-57 | 6 | 0 | Len Barker | Britt Burns | Len Barker | Britt Burns | | 539 | 570 | -31 |
| 1980-08-18 | @ CHA | 116 | L 2-7 | 59-57 | 6 | 16,270 | Wayne Garland | Steve Trout | Steve Trout | Wayne Garland | | 541 | 577 | -36 |
| 1980-08-19 | @ CHA | 117 | W 8-5 | 60-57 | 6 | 10,001 | Ross Grimsley | Richard Dotson | Ross Grimsley | Richard Dotson | Sid Monge | 549 | 582 | -33 |
| 1980-08-20 | @ CHA | 118 | W 3-0 | 61-57 | 6 | 8,696 | Dan Spillner | Ken Kravec | Dan Spillner | Ken Kravec | | 552 | 582 | -30 |
| 1980-08-21 | @ KCA | 119 | W 4-3 | 62-57 | 6 | 32,139 | Rick Waits | Steve Busby | Rick Waits | Steve Busby | Victor Cruz | 556 | 585 | -29 |
| 1980-08-22 | @ KCA | 120 | W 4-1 | 63-57 | 5 | 34,526 | Len Barker | Paul Splittorff | Len Barker | Paul Splittorff | Sid Monge | 560 | 586 | -26 |
| 1980-08-23 | @ KCA | 121 | L 2-3 | 63-58 | 6 | 40,192 | Wayne Garland | Rich Gale | Rich Gale | Wayne Garland | Dan Quisenberry | 562 | 589 | -27 |
| 1980-08-24 | @ KCA | 122 | L 5-7 | 63-59 | 6 | 30,593 | Ross Grimsley | Dennis Leonard | Dennis Leonard | Ross Grimsley | Dan Quisenberry | 567 | 596 | -29 |
| 1980-08-25 | vs MIN | 123 | W 4-3 | 64-59 | 6 | 14,211 | Dan Spillner | Fernando Arroyo | Dan Spillner | Fernando Arroyo | Sid Monge | 571 | 599 | -28 |
| 1980-08-26 | vs MIN | 124 | L 1-5 | 64-60 | 6 | 6,483 | Rick Waits | Roger Erickson | Roger Erickson | Rick Waits | | 572 | 604 | -32 |
| 1980-08-27 | vs MIN | 125 | W 4-1 | 65-60 | 5 | 7,572 | Len Barker | Jerry Koosman | Len Barker | Jerry Koosman | Victor Cruz | 576 | 605 | -29 |
| 1980-08-29 | vs CHA | 126 | W 6-5 | 66-60 | 5 | 9,044 | Wayne Garland | Richard Dotson | Sid Monge | Ed Farmer | Victor Cruz | 582 | 610 | -28 |
| 1980-08-30 | vs CHA | 127 | W 6-2 | 67-60 | 5 | 11,787 | Dan Spillner | Ross Baumgarten | Dan Spillner | Ross Baumgarten | Victor Cruz | 588 | 612 | -24 |
| 1980-08-31 | vs CHA | 128 | L 8-10 | 67-62 | 5 | 0 | Rick Waits | LaMarr Hoyt | LaMarr Hoyt | Victor Cruz | Ed Farmer | 596 | 622 | -26 |
| 1980-08-31 | vs CHA | 129 | L 7-8 | 67-62 | 5 | 19,131 | Ross Grimsley | Steve Trout | Steve Trout | Ross Grimsley | Ed Farmer | 603 | 630 | -27 |
| 1980-09-01 | @ MIN | 130 | W 5-2 | 68-62 | 4 | 4,304 | Len Barker | Albert Williams | Len Barker | Albert Williams | | 608 | 632 | -24 |
| 1980-09-02 | @ MIN | 131 | L 3-5 | 68-63 | 6 | 2,934 | Wayne Garland | Darrell Jackson | Darrell Jackson | Wayne Garland | Doug Corbett | 611 | 637 | -26 |
| 1980-09-03 | @ MIN | 132 | W 7-1 | 69-63 | 6 | 2,877 | Dan Spillner | Geoff Zahn | Dan Spillner | Geoff Zahn | | 618 | 638 | -20 |
| 1980-09-05 | vs KCA | 133 | L 1-2 | 69-64 | 6 | 21,808 | Rick Waits | Paul Splittorff | Paul Splittorff | Rick Waits | | 619 | 640 | -21 |
| 1980-09-06 | vs KCA | 134 | W 8-3 | 70-64 | 6 | 27,352 | Len Barker | Renie Martin | Len Barker | Renie Martin | | 627 | 643 | -16 |
| 1980-09-07 | vs KCA | 135 | L 4-6 | 70-65 | 6 | 8,990 | Wayne Garland | Dennis Leonard | Dennis Leonard | Wayne Garland | Dan Quisenberry | 631 | 649 | -18 |
| 1980-09-08 | vs BOS | 136 | L 4-10 | 70-66 | 6 | 5,506 | Dan Spillner | Mike Torrez | Mike Torrez | Dan Spillner | | 635 | 659 | -24 |
| 1980-09-09 | vs BOS | 137 | L 3-4 | 70-67 | 6 | 5,182 | Ross Grimsley | Dennis Eckersley | Dennis Eckersley | Victor Cruz | Tom Burgmeier | 638 | 663 | -25 |
| 1980-09-10 | vs BOS | 138 | W 7-4 | 71-67 | 5 | 5,242 | Rick Waits | John Tudor | Rick Waits | John Tudor | | 645 | 667 | -22 |
| 1980-09-12 | vs DET | 139 | L 3-6 | 71-68 | 6 | 9,961 | Len Barker | Mark Fidrych | Aurelio Lopez | Len Barker | | 648 | 673 | -25 |
| 1980-09-13 | vs DET | 140 | L 4-7 | 71-69 | 6 | 6,380 | Wayne Garland | Milt Wilcox | Pat Underwood | Mike Stanton | Dave Rozema | 652 | 680 | -28 |
| 1980-09-14 | vs DET | 141 | W 5-4 | 73-69 | 5 | 0 | Dan Spillner | Dan Schatzeder | Victor Cruz | Aurelio Lopez | | 657 | 684 | -27 |
| 1980-09-14 | vs DET | 142 | W 3-0 | 73-69 | 5 | 10,189 | Bob Owchinko | Dan Petry | Bob Owchinko | Dan Petry | | 660 | 684 | -24 |
| 1980-09-16 | @ BOS | 143 | L 5-9 | 73-70 | 6 | 14,630 | Ross Grimsley | John Tudor | John Tudor | Ross Grimsley | Bob Stanley | 665 | 693 | -28 |
| 1980-09-17 | @ BOS | 144 | W 6-5 | 74-70 | 5 | 15,321 | Len Barker | Dick Drago | Dan Spillner | Mike Torrez | | 671 | 698 | -27 |
| 1980-09-18 | @ BOS | 145 | L 3-8 | 74-71 | 5 | 14,845 | Wayne Garland | Steve Crawford | Steve Crawford | Wayne Garland | | 674 | 706 | -32 |
| 1980-09-19 | @ DET | 146 | L 3-4 | 74-72 | 6 | 10,822 | Bob Owchinko | Dan Schatzeder | Dan Schatzeder | Bob Owchinko | Aurelio Lopez | 677 | 710 | -33 |
| 1980-09-20 | @ DET | 147 | L 3-13 | 74-73 | 6 | 10,985 | Rick Waits | Dan Petry | Dan Petry | Rick Waits | | 680 | 723 | -43 |
| 1980-09-21 | @ DET | 148 | L 1-13 | 74-74 | 6 | 10,682 | Dan Spillner | Jack Morris | Jack Morris | Dan Spillner | Pat Underwood | 681 | 736 | -55 |
| 1980-09-22 | @ NYA | 149 | L 3-4 | 74-75 | 6 | 16,024 | Len Barker | Tommy John | Tommy John | Len Barker | Rich Gossage | 684 | 740 | -56 |
| 1980-09-23 | @ NYA | 150 | L 4-5 | 74-76 | 6 | 24,061 | Wayne Garland | Rudy May | Ron Davis | Mike Stanton | | 688 | 745 | -57 |
| 1980-09-24 | @ NYA | 151 | L 3-7 | 74-77 | 6 | 22,159 | Bob Owchinko | Luis Tiant | Luis Tiant | Bob Owchinko | Tom Underwood | 691 | 752 | -61 |
| 1980-09-25 | @ NYA | 152 | W 5-0 | 75-77 | 6 | 21,441 | Rick Waits | Gaylord Perry | Rick Waits | Gaylord Perry | | 696 | 752 | -56 |
| 1980-09-26 | vs BAL | 153 | W 5-4 | 76-77 | 6 | 6,362 | Dan Spillner | Mike Flanagan | Dan Spillner | Mike Flanagan | Sid Monge | 701 | 756 | -55 |
| 1980-09-27 | vs BAL | 154 | W 6-5 | 77-77 | 6 | 9,989 | Len Barker | Scott McGregor | Len Barker | Tippy Martinez | Sid Monge | 707 | 761 | -54 |
| 1980-09-28 | vs BAL | 155 | L 3-5 | 77-78 | 6 | 10,631 | Bob Owchinko | Jim Palmer | Jim Palmer | Bob Owchinko | Tim Stoddard | 710 | 766 | -56 |
| 1980-09-30 | vs NYA | 156 | W 12-9 | 78-78 | 6 | 11,919 | Rick Waits | Luis Tiant | Sid Monge | Rich Gossage | Sandy Wihtol | 722 | 775 | -53 |
| 1980-10-01 | vs NYA | 157 | L 7-18 | 78-79 | 6 | 19,037 | Len Barker | Tommy John | Gaylord Perry | Len Barker | | 729 | 793 | -64 |
| 1980-10-04 | @ BAL | 158 | L 2-3 | 79-80 | 6 | 0 | Bob Owchinko | Steve Stone | Sammy Stewart | Sid Monge | | 731 | 796 | -65 |
| 1980-10-04 | @ BAL | 159 | W 6-4 | 79-80 | 6 | 15,755 | Rick Waits | Mike Boddicker | Rick Waits | Mike Boddicker | | 737 | 800 | -63 |
| 1980-10-05 | @ BAL | 160 | L 1-7 | 79-81 | 6 | 20,407 | Len Barker | Scott McGregor | Scott McGregor | Len Barker | | 738 | 807 | -69 |