| 1980-04-09 | vs TOR | 1 | W 8-6 | 1-0 | 1 | 22,588 | Mike Parrott | Dave Lemanczyk | Mike Parrott | Dave Lemanczyk | Dave Heaverlo | 8 | 6 | 2 |
| 1980-04-11 | vs TOR | 2 | L 7-10 | 1-1 | 7 | 6,104 | Jim Beattie | Dave Stieb | Balor Moore | Rob Dressler | | 15 | 16 | -1 |
| 1980-04-12 | vs TOR | 3 | W 3-2 | 2-1 | 5 | 6,773 | Rick Honeycutt | Paul Mirabella | Rick Honeycutt | Jerry Garvin | | 18 | 18 | 0 |
| 1980-04-13 | vs TOR | 4 | W 5-1 | 3-1 | 3 | 4,567 | Floyd Bannister | Dave Lemanczyk | Floyd Bannister | Dave Lemanczyk | | 23 | 19 | 4 |
| 1980-04-14 | @ OAK | 5 | W 7-1 | 4-1 | 1 | 5,260 | Glenn Abbott | Steve McCatty | Glenn Abbott | Steve McCatty | | 30 | 20 | 10 |
| 1980-04-15 | @ OAK | 6 | L 3-12 | 4-2 | 2 | 2,140 | Mike Parrott | Steve McCatty | Steve McCatty | Mike Parrott | | 33 | 32 | 1 |
| 1980-04-16 | @ OAK | 7 | L 1-6 | 4-3 | 5 | 2,418 | Jim Beattie | Matt Keough | Matt Keough | Jim Beattie | | 34 | 38 | -4 |
| 1980-04-17 | vs MIN | 8 | W 4-3 | 5-3 | 4 | 5,466 | Rick Honeycutt | Geoff Zahn | Rick Honeycutt | Geoff Zahn | | 38 | 41 | -3 |
| 1980-04-18 | vs MIN | 9 | W 3-1 | 7-3 | 2 | 0 | Floyd Bannister | Roger Erickson | Floyd Bannister | Roger Erickson | | 41 | 42 | -1 |
| 1980-04-18 | vs MIN | 10 | W 3-2 | 7-3 | 2 | 7,006 | Gary Wheelock | Terry Felton | Byron McLaughlin | Terry Felton | Shane Rawley | 44 | 44 | 0 |
| 1980-04-19 | vs MIN | 11 | L 3-8 | 7-4 | 4 | 11,151 | Glenn Abbott | Jerry Koosman | Jerry Koosman | Glenn Abbott | | 47 | 52 | -5 |
| 1980-04-20 | vs MIN | 12 | L 3-4 | 7-5 | 4 | 8,225 | Mike Parrott | Pete Redfern | Pete Redfern | Mike Parrott | Mike Marshall | 50 | 56 | -6 |
| 1980-04-21 | vs OAK | 13 | L 2-4 | 7-6 | 4 | 4,466 | Jim Beattie | Dave Hamilton | Jeff Jones | Shane Rawley | | 52 | 60 | -8 |
| 1980-04-22 | vs OAK | 14 | W 5-4 | 8-6 | 4 | 4,059 | Rick Honeycutt | Brian Kingman | Rick Honeycutt | Brian Kingman | Byron McLaughlin | 57 | 64 | -7 |
| 1980-04-23 | vs OAK | 15 | L 2-5 | 8-7 | 5 | 4,075 | Floyd Bannister | Mike Norris | Rick Langford | Byron McLaughlin | | 59 | 69 | -10 |
| 1980-04-25 | vs CAL | 16 | L 3-4 | 8-8 | 5 | 9,083 | Mike Parrott | Don Aase | Don Aase | Mike Parrott | John Montague | 62 | 73 | -11 |
| 1980-04-26 | vs CAL | 17 | L 6-7 | 8-9 | 7 | 20,152 | Jim Beattie | Chris Knapp | Dave LaRoche | Rob Dressler | Mark Clear | 68 | 80 | -12 |
| 1980-04-27 | vs CAL | 18 | W 7-3 | 9-9 | 6 | 6,109 | Glenn Abbott | Dave Frost | Glenn Abbott | Dave Frost | | 75 | 83 | -8 |
| 1980-04-28 | @ MIN | 19 | W 6-4 | 10-9 | 5 | 2,544 | Rick Honeycutt | Terry Felton | Rick Honeycutt | Terry Felton | Dave Heaverlo | 81 | 87 | -6 |
| 1980-04-29 | @ MIN | 20 | W 5-3 | 11-9 | 4 | 2,580 | Floyd Bannister | Jerry Koosman | Shane Rawley | Mike Marshall | | 86 | 90 | -4 |
| 1980-04-30 | @ MIN | 21 | L 3-10 | 11-10 | 5 | 2,891 | Mike Parrott | Pete Redfern | Pete Redfern | Mike Parrott | | 89 | 100 | -11 |
| 1980-05-01 | @ CAL | 22 | L 1-2 | 11-11 | 6 | 22,260 | Jim Beattie | Chris Knapp | John Montague | Jim Beattie | | 90 | 102 | -12 |
| 1980-05-02 | @ CAL | 23 | L 1-3 | 11-12 | 6 | 29,674 | Glenn Abbott | Dave Frost | Dave Frost | Glenn Abbott | | 91 | 105 | -14 |
| 1980-05-03 | @ CAL | 24 | W 2-0 | 12-12 | 5 | 40,376 | Rick Honeycutt | Bruce Kison | Rick Honeycutt | Bruce Kison | | 93 | 105 | -12 |
| 1980-05-04 | @ CAL | 25 | L 3-4 | 12-13 | 6 | 27,584 | Floyd Bannister | Frank Tanana | Frank Tanana | Floyd Bannister | Mark Clear | 96 | 109 | -13 |
| 1980-05-06 | vs DET | 26 | L 5-9 | 12-14 | 6 | 5,821 | Jim Beattie | Dan Petry | Dan Petry | Jim Beattie | Aurelio Lopez | 101 | 118 | -17 |
| 1980-05-07 | vs DET | 27 | W 7-6 | 13-14 | 5 | 4,934 | Glenn Abbott | Dave Rozema | Dave Heaverlo | Pat Underwood | | 108 | 124 | -16 |
| 1980-05-08 | vs DET | 28 | W 4-3 | 14-14 | 5 | 6,950 | Rick Honeycutt | Jack Morris | Rick Honeycutt | Jack Morris | | 112 | 127 | -15 |
| 1980-05-09 | vs CLE | 29 | L 1-4 | 14-15 | 5 | 23,229 | Floyd Bannister | Dan Spillner | Dan Spillner | Floyd Bannister | | 113 | 131 | -18 |
| 1980-05-10 | vs CLE | 30 | L 3-5 | 14-16 | 5 | 10,690 | Byron McLaughlin | John Denny | John Denny | Byron McLaughlin | Victor Cruz | 116 | 136 | -20 |
| 1980-05-11 | vs CLE | 31 | W 9-4 | 15-16 | 5 | 6,683 | Jim Beattie | Len Barker | Jim Beattie | Len Barker | | 125 | 140 | -15 |
| 1980-05-14 | @ TOR | 32 | W 7-0 | 16-16 | 5 | 13,055 | Glenn Abbott | Paul Mirabella | Glenn Abbott | Paul Mirabella | | 132 | 140 | -8 |
| 1980-05-15 | @ TOR | 33 | L 0-1 | 16-17 | 5 | 11,579 | Floyd Bannister | Jim Clancy | Jim Clancy | Floyd Bannister | | 132 | 141 | -9 |
| 1980-05-16 | @ CHA | 34 | W 4-2 | 17-17 | 5 | 12,689 | Jim Beattie | Steve Trout | Jim Beattie | Steve Trout | Shane Rawley | 136 | 143 | -7 |
| 1980-05-17 | @ CHA | 35 | L 0-4 | 17-18 | 5 | 8,419 | Rick Honeycutt | Britt Burns | Britt Burns | Rick Honeycutt | | 136 | 147 | -11 |
| 1980-05-18 | @ CHA | 36 | L 5-6 | 17-19 | 5 | 24,625 | Rob Dressler | Francisco Barrios | Francisco Barrios | Rob Dressler | Ed Farmer | 141 | 153 | -12 |
| 1980-05-19 | vs MIL | 37 | W 4-3 | 18-19 | 5 | 5,767 | Glenn Abbott | Moose Haas | Shane Rawley | Bill Castro | | 145 | 156 | -11 |
| 1980-05-20 | vs MIL | 38 | L 5-14 | 18-20 | 5 | 6,243 | Floyd Bannister | Lary Sorensen | Lary Sorensen | Floyd Bannister | | 150 | 170 | -20 |
| 1980-05-21 | vs MIL | 39 | W 6-5 | 19-20 | 5 | 8,219 | Jim Beattie | Mike Caldwell | Jim Beattie | Mike Caldwell | Dave Heaverlo | 156 | 175 | -19 |
| 1980-05-23 | vs CHA | 40 | W 8-0 | 20-20 | 5 | 7,009 | Rick Honeycutt | Britt Burns | Rick Honeycutt | Britt Burns | Shane Rawley | 164 | 175 | -11 |
| 1980-05-24 | vs CHA | 41 | W 5-4 | 21-20 | 5 | 24,048 | Glenn Abbott | Ken Kravec | Glenn Abbott | Ken Kravec | Dave Roberts | 169 | 179 | -10 |
| 1980-05-25 | vs CHA | 42 | W 8-3 | 22-20 | 4 | 8,071 | Floyd Bannister | Richard Dotson | Floyd Bannister | Randy Scarbery | | 177 | 182 | -5 |
| 1980-05-26 | @ MIL | 43 | L 1-11 | 22-21 | 5 | 26,302 | Mike Parrott | Mike Caldwell | Mike Caldwell | Mike Parrott | | 178 | 193 | -15 |
| 1980-05-27 | @ MIL | 44 | L 1-4 | 22-22 | 5 | 11,904 | Jim Beattie | Rickey Keeton | Rickey Keeton | Jim Beattie | Bob McClure | 179 | 197 | -18 |
| 1980-05-28 | @ MIL | 45 | L 0-7 | 22-23 | 5 | 10,627 | Byron McLaughlin | Bill Travers | Bill Travers | Byron McLaughlin | Reggie Cleveland | 179 | 204 | -25 |
| 1980-05-30 | @ CLE | 46 | W 4-3 | 23-23 | 4 | 18,161 | Floyd Bannister | Len Barker | Dave Heaverlo | Sid Monge | | 183 | 207 | -24 |
| 1980-05-31 | @ CLE | 47 | L 2-5 | 23-24 | 4 | 11,107 | Mike Parrott | Dan Spillner | Dan Spillner | Mike Parrott | | 185 | 212 | -27 |
| 1980-06-01 | @ CLE | 48 | W 8-7 | 24-24 | 4 | 25,376 | Jim Beattie | Rick Waits | Dave Heaverlo | Sid Monge | | 193 | 219 | -26 |
| 1980-06-02 | @ DET | 49 | L 3-3 | 24-25 | 4 | 12,291 | Rick Honeycutt | Jack Morris | | | | 196 | 222 | -26 |
| 1980-06-03 | @ DET | 50 | L 2-4 | 24-26 | 4 | 13,942 | Dave Roberts | Dan Petry | Aurelio Lopez | Byron McLaughlin | | 198 | 226 | -28 |
| 1980-06-04 | @ DET | 51 | L 2-8 | 24-27 | 5 | 14,566 | Floyd Bannister | Milt Wilcox | Milt Wilcox | Floyd Bannister | | 200 | 234 | -34 |
| 1980-06-06 | vs NYA | 52 | L 0-3 | 24-28 | 4 | 28,156 | Jim Beattie | Tommy John | Tommy John | Jim Beattie | | 200 | 237 | -37 |
| 1980-06-07 | vs NYA | 53 | L 0-1 | 24-29 | 4 | 43,594 | Rick Honeycutt | Tom Underwood | Tom Underwood | Rick Honeycutt | Rich Gossage | 200 | 238 | -38 |
| 1980-06-08 | vs NYA | 54 | W 5-0 | 25-29 | 4 | 22,175 | Glenn Abbott | Ron Guidry | Glenn Abbott | Ron Guidry | | 205 | 238 | -33 |
| 1980-06-09 | vs BOS | 55 | W 8-7 | 26-29 | 4 | 10,132 | Mike Parrott | Bob Stanley | Dave Heaverlo | Dick Drago | | 213 | 245 | -32 |
| 1980-06-10 | vs BOS | 56 | L 4-5 | 26-30 | 4 | 10,223 | Floyd Bannister | Steve Renko | Skip Lockwood | Rob Dressler | | 217 | 250 | -33 |
| 1980-06-11 | vs BOS | 57 | L 5-7 | 26-31 | 4 | 10,086 | Jim Beattie | Chuck Rainey | Chuck Rainey | Jim Beattie | Tom Burgmeier | 222 | 257 | -35 |
| 1980-06-12 | vs BAL | 58 | L 1-4 | 26-32 | 4 | 10,049 | Rick Honeycutt | Steve Stone | Steve Stone | Rick Honeycutt | | 223 | 261 | -38 |
| 1980-06-13 | vs BAL | 59 | W 7-6 | 27-32 | 4 | 10,048 | Glenn Abbott | Mike Flanagan | Glenn Abbott | Mike Flanagan | Dave Heaverlo | 230 | 267 | -37 |
| 1980-06-14 | vs BAL | 60 | W 9-8 | 28-32 | 4 | 15,856 | Dave Roberts | Scott McGregor | Dave Roberts | Paul Hartzell | Shane Rawley | 239 | 275 | -36 |
| 1980-06-15 | vs BAL | 61 | L 3-9 | 28-33 | 4 | 23,674 | Floyd Bannister | Sammy Stewart | Sammy Stewart | Floyd Bannister | | 242 | 284 | -42 |
| 1980-06-16 | @ NYA | 62 | L 3-6 | 28-34 | 4 | 20,862 | Jim Beattie | Tommy John | Tommy John | Jim Beattie | Rich Gossage | 245 | 290 | -45 |
| 1980-06-17 | @ NYA | 63 | L 2-8 | 28-35 | 4 | 20,835 | Rick Honeycutt | Tom Underwood | Tom Underwood | Rick Honeycutt | Ron Davis | 247 | 298 | -51 |
| 1980-06-18 | @ BOS | 64 | L 2-6 | 28-36 | 5 | 22,230 | Glenn Abbott | Dennis Eckersley | Dennis Eckersley | Glenn Abbott | | 249 | 304 | -55 |
| 1980-06-19 | @ BOS | 65 | L 0-2 | 28-37 | 5 | 23,032 | Mike Parrott | Bob Stanley | Bob Stanley | Mike Parrott | | 249 | 306 | -57 |
| 1980-06-20 | @ BAL | 66 | W 3-1 | 29-37 | 5 | 23,107 | Floyd Bannister | Jim Palmer | Floyd Bannister | Jim Palmer | | 252 | 307 | -55 |
| 1980-06-21 | @ BAL | 67 | L 0-9 | 29-38 | 5 | 28,371 | Dave Roberts | Steve Stone | Steve Stone | Dave Roberts | | 252 | 316 | -64 |
| 1980-06-22 | @ BAL | 68 | W 7-5 | 30-38 | 5 | 42,497 | Rick Honeycutt | Mike Flanagan | Shane Rawley | Tim Stoddard | | 259 | 321 | -62 |
| 1980-06-24 | @ TEX | 69 | L 4-5 | 30-39 | 5 | 11,324 | Glenn Abbott | Doc Medich | Sparky Lyle | Shane Rawley | | 263 | 326 | -63 |
| 1980-06-25 | @ TEX | 70 | L 1-6 | 30-40 | 5 | 14,029 | Mike Parrott | Fergie Jenkins | Fergie Jenkins | Mike Parrott | | 264 | 332 | -68 |
| 1980-06-26 | @ TEX | 71 | W 8-4 | 31-40 | 5 | 9,531 | Floyd Bannister | Jon Matlack | Floyd Bannister | Jon Matlack | Shane Rawley | 272 | 336 | -64 |
| 1980-06-27 | vs KCA | 72 | L 1-2 | 31-41 | 5 | 12,099 | Rick Honeycutt | Rich Gale | Rich Gale | Rick Honeycutt | Dan Quisenberry | 273 | 338 | -65 |
| 1980-06-28 | vs KCA | 73 | L 2-4 | 31-42 | 5 | 22,154 | Dave Roberts | Larry Gura | Larry Gura | Dave Roberts | | 275 | 342 | -67 |
| 1980-06-29 | vs KCA | 74 | W 7-2 | 32-42 | 5 | 10,015 | Glenn Abbott | Dennis Leonard | Glenn Abbott | Dennis Leonard | | 282 | 344 | -62 |
| 1980-06-30 | vs TEX | 75 | L 5-11 | 32-43 | 5 | 5,658 | Mike Parrott | Fergie Jenkins | Fergie Jenkins | Mike Parrott | | 287 | 355 | -68 |
| 1980-07-01 | vs TEX | 76 | W 6-5 | 33-43 | 4 | 6,005 | Floyd Bannister | Jon Matlack | Shane Rawley | Jim Kern | | 293 | 360 | -67 |
| 1980-07-02 | vs TEX | 77 | L 3-6 | 33-44 | 5 | 8,692 | Rick Honeycutt | Gaylord Perry | Gaylord Perry | Rick Honeycutt | | 296 | 366 | -70 |
| 1980-07-03 | @ KCA | 78 | W 13-2 | 34-44 | 5 | 21,777 | Jim Beattie | Larry Gura | Jim Beattie | Larry Gura | Shane Rawley | 309 | 368 | -59 |
| 1980-07-04 | @ KCA | 79 | L 3-5 | 34-45 | 5 | 27,891 | Glenn Abbott | Dennis Leonard | Dan Quisenberry | Dave Roberts | | 312 | 373 | -61 |
| 1980-07-05 | @ KCA | 80 | L 4-5 | 34-46 | 6 | 30,617 | Mike Parrott | Renie Martin | Jeff Twitty | Mike Parrott | Dan Quisenberry | 316 | 378 | -62 |
| 1980-07-06 | @ KCA | 81 | W 5-3 | 35-46 | 6 | 28,458 | Floyd Bannister | Paul Splittorff | Floyd Bannister | Paul Splittorff | Shane Rawley | 321 | 381 | -60 |
| 1980-07-10 | vs MIN | 82 | L 4-12 | 35-47 | 6 | 9,051 | Rick Honeycutt | Jerry Koosman | Jerry Koosman | Rick Honeycutt | | 325 | 393 | -68 |
| 1980-07-11 | vs MIN | 83 | L 3-6 | 35-48 | 6 | 7,688 | Glenn Abbott | Darrell Jackson | Darrell Jackson | Glenn Abbott | Doug Corbett | 328 | 399 | -71 |
| 1980-07-12 | @ MIN | 84 | L 3-8 | 35-49 | 6 | 14,963 | Floyd Bannister | Geoff Zahn | Geoff Zahn | Floyd Bannister | | 331 | 407 | -76 |
| 1980-07-13 | @ MIN | 85 | L 6-7 | 35-50 | 6 | 8,573 | Jim Beattie | Roger Erickson | Doug Corbett | Shane Rawley | | 337 | 414 | -77 |
| 1980-07-14 | @ MIN | 86 | W 8-5 | 36-50 | 6 | 11,060 | Rick Honeycutt | Fernando Arroyo | Rick Honeycutt | Fernando Arroyo | Dave Roberts | 345 | 419 | -74 |
| 1980-07-16 | vs TOR | 87 | L 0-5 | 36-51 | 6 | 5,644 | Glenn Abbott | Dave Stieb | Dave Stieb | Glenn Abbott | | 345 | 424 | -79 |
| 1980-07-17 | vs TOR | 88 | W 5-3 | 37-51 | 6 | 5,726 | Floyd Bannister | Paul Mirabella | Shane Rawley | Jesse Jefferson | | 350 | 427 | -77 |
| 1980-07-18 | vs DET | 89 | L 3-5 | 37-52 | 6 | 7,479 | Jim Beattie | Dan Petry | Aurelio Lopez | Jim Beattie | | 353 | 432 | -79 |
| 1980-07-19 | vs DET | 90 | L 3-5 | 37-53 | 6 | 16,525 | Rick Honeycutt | Bruce Robbins | Dave Rozema | Rick Honeycutt | | 356 | 437 | -81 |
| 1980-07-20 | vs DET | 91 | L 2-5 | 37-54 | 6 | 7,583 | Mike Parrott | Dan Schatzeder | Dan Schatzeder | Mike Parrott | | 358 | 442 | -84 |
| 1980-07-21 | vs CLE | 92 | W 7-0 | 38-54 | 6 | 5,050 | Glenn Abbott | Wayne Garland | Glenn Abbott | Wayne Garland | | 365 | 442 | -77 |
| 1980-07-22 | vs CLE | 93 | L 0-4 | 38-55 | 6 | 5,727 | Floyd Bannister | Len Barker | Len Barker | Floyd Bannister | | 365 | 446 | -81 |
| 1980-07-23 | vs CLE | 94 | L 6-12 | 38-56 | 6 | 6,387 | Jim Beattie | Bob Owchinko | Victor Cruz | Shane Rawley | | 371 | 458 | -87 |
| 1980-07-25 | @ TOR | 95 | L 3-5 | 38-57 | 6 | 16,248 | Rick Honeycutt | Jim Clancy | Jim Clancy | Rick Honeycutt | | 374 | 463 | -89 |
| 1980-07-26 | @ TOR | 96 | W 7-2 | 39-58 | 6 | 0 | Rob Dressler | Dave Stieb | Rob Dressler | Dave Stieb | | 381 | 465 | -84 |
| 1980-07-26 | @ TOR | 97 | L 5-7 | 39-58 | 6 | 18,067 | Glenn Abbott | Balor Moore | Jack Kucek | Glenn Abbott | Jerry Garvin | 386 | 472 | -86 |
| 1980-07-27 | @ TOR | 98 | L 0-5 | 39-59 | 6 | 17,080 | Floyd Bannister | Jesse Jefferson | Jesse Jefferson | Floyd Bannister | | 386 | 477 | -91 |
| 1980-07-28 | @ CLE | 99 | L 3-7 | 39-60 | 6 | 5,712 | Jim Beattie | Len Barker | Len Barker | Jim Beattie | Victor Cruz | 389 | 484 | -95 |
| 1980-07-29 | @ CLE | 100 | L 2-7 | 39-61 | 6 | 8,600 | Rick Honeycutt | Dan Spillner | Dan Spillner | Rick Honeycutt | Sid Monge | 391 | 491 | -100 |
| 1980-07-30 | @ CLE | 101 | L 2-5 | 39-62 | 6 | 10,352 | Glenn Abbott | Ross Grimsley | Ross Grimsley | Glenn Abbott | | 393 | 496 | -103 |
| 1980-08-01 | @ DET | 102 | L 0-1 | 39-64 | 6 | 0 | Floyd Bannister | Jack Morris | Jack Morris | Floyd Bannister | | 393 | 497 | -104 |
| 1980-08-01 | @ DET | 103 | L 2-5 | 39-64 | 6 | 32,910 | Rob Dressler | Dan Petry | Dan Petry | Rob Dressler | Aurelio Lopez | 395 | 502 | -107 |
| 1980-08-02 | @ DET | 104 | L 3-9 | 39-65 | 7 | 23,278 | Jim Beattie | Bruce Robbins | Bruce Robbins | Jim Beattie | Aurelio Lopez | 398 | 511 | -113 |
| 1980-08-03 | @ DET | 105 | L 3-4 | 39-66 | 7 | 25,454 | Rick Honeycutt | Roger Weaver | Dave Rozema | Rick Honeycutt | Aurelio Lopez | 401 | 515 | -114 |
| 1980-08-04 | @ CAL | 106 | L 3-8 | 39-67 | 7 | 31,634 | Glenn Abbott | Frank Tanana | Andy Hassler | Shane Rawley | | 404 | 523 | -119 |
| 1980-08-05 | @ CAL | 107 | L 4-5 | 39-68 | 7 | 22,326 | Floyd Bannister | Jim Barr | Mark Clear | Dave Heaverlo | | 408 | 528 | -120 |
| 1980-08-06 | @ CAL | 108 | L 3-8 | 39-69 | 7 | 22,599 | Rob Dressler | Chris Knapp | John Montague | Rob Dressler | | 411 | 536 | -125 |
| 1980-08-08 | @ OAK | 109 | W 2-1 | 40-69 | 7 | 6,283 | Jim Beattie | Matt Keough | Shane Rawley | Matt Keough | Dave Roberts | 413 | 537 | -124 |
| 1980-08-09 | @ OAK | 110 | L 1-2 | 40-70 | 7 | 13,629 | Rick Honeycutt | Mike Norris | Mike Norris | Rick Honeycutt | | 414 | 539 | -125 |
| 1980-08-10 | @ OAK | 111 | W 2-1 | 41-71 | 7 | 0 | Glenn Abbott | Steve McCatty | Dave Heaverlo | Steve McCatty | Shane Rawley | 416 | 540 | -124 |
| 1980-08-10 | @ OAK | 112 | L 1-6 | 41-71 | 7 | 13,062 | Byron McLaughlin | Rick Langford | Rick Langford | Byron McLaughlin | | 417 | 546 | -129 |
| 1980-08-12 | vs CAL | 113 | L 6-9 | 41-72 | 7 | 16,313 | Rob Dressler | Chris Knapp | Mark Clear | Dave Heaverlo | | 423 | 555 | -132 |
| 1980-08-13 | vs CAL | 114 | L 4-10 | 41-73 | 7 | 9,369 | Jim Beattie | Dave LaRoche | Andy Hassler | Shane Rawley | | 427 | 565 | -138 |
| 1980-08-14 | vs CAL | 115 | L 1-2 | 41-74 | 7 | 7,326 | Rick Honeycutt | Alfredo Martinez | Alfredo Martinez | Rick Honeycutt | Don Aase | 428 | 567 | -139 |
| 1980-08-15 | vs OAK | 116 | L 3-11 | 41-75 | 7 | 6,238 | Glenn Abbott | Rick Langford | Rick Langford | Glenn Abbott | | 431 | 578 | -147 |
| 1980-08-16 | vs OAK | 117 | L 3-8 | 41-76 | 7 | 17,111 | Byron McLaughlin | Steve McCatty | Steve McCatty | Byron McLaughlin | | 434 | 586 | -152 |
| 1980-08-17 | vs OAK | 118 | W 4-3 | 42-76 | 7 | 5,484 | Rob Dressler | Brian Kingman | Rob Dressler | Brian Kingman | Shane Rawley | 438 | 589 | -151 |
| 1980-08-19 | vs NYA | 119 | L 1-3 | 42-77 | 7 | 15,043 | Rick Honeycutt | Tom Underwood | Tom Underwood | Rick Honeycutt | Rich Gossage | 439 | 592 | -153 |
| 1980-08-20 | vs NYA | 120 | L 4-6 | 42-78 | 7 | 14,143 | Glenn Abbott | Tommy John | Tommy John | Glenn Abbott | Rich Gossage | 443 | 598 | -155 |
| 1980-08-21 | vs NYA | 121 | W 6-4 | 43-78 | 7 | 16,400 | Floyd Bannister | Gaylord Perry | Dave Roberts | Gaylord Perry | Shane Rawley | 449 | 602 | -153 |
| 1980-08-22 | vs BOS | 122 | L 0-1 | 43-79 | 7 | 10,792 | Jim Beattie | Steve Renko | Steve Renko | Jim Beattie | Bob Stanley | 449 | 603 | -154 |
| 1980-08-23 | vs BOS | 123 | W 3-1 | 44-79 | 7 | 16,072 | Rob Dressler | Bruce Hurst | Rob Dressler | Bruce Hurst | Shane Rawley | 452 | 604 | -152 |
| 1980-08-24 | vs BOS | 124 | L 7-10 | 44-80 | 7 | 16,920 | Rick Honeycutt | Mike Torrez | Bill Campbell | Rick Honeycutt | | 459 | 614 | -155 |
| 1980-08-25 | vs BAL | 125 | W 10-5 | 45-80 | 7 | 6,478 | Glenn Abbott | Dennis Martinez | Glenn Abbott | Dennis Martinez | Shane Rawley | 469 | 619 | -150 |
| 1980-08-26 | vs BAL | 126 | W 2-1 | 46-80 | 7 | 7,767 | Floyd Bannister | Scott McGregor | Floyd Bannister | Scott McGregor | | 471 | 620 | -149 |
| 1980-08-28 | @ NYA | 127 | L 5-6 | 46-81 | 7 | 30,215 | Jim Beattie | Rudy May | Ron Guidry | Jim Beattie | | 476 | 626 | -150 |
| 1980-08-29 | @ NYA | 128 | L 1-5 | 46-82 | 7 | 30,005 | Rob Dressler | Tommy John | Tommy John | Rob Dressler | | 477 | 631 | -154 |
| 1980-08-30 | @ NYA | 129 | L 3-9 | 46-83 | 7 | 40,047 | Glenn Abbott | Gaylord Perry | Gaylord Perry | Glenn Abbott | | 480 | 640 | -160 |
| 1980-08-31 | @ NYA | 130 | W 1-0 | 47-83 | 7 | 43,024 | Floyd Bannister | Luis Tiant | Shane Rawley | Ron Guidry | | 481 | 640 | -159 |
| 1980-09-01 | @ BAL | 131 | L 4-5 | 47-84 | 7 | 40,304 | Mike Parrott | Dennis Martinez | Dennis Martinez | Mike Parrott | Tippy Martinez | 485 | 645 | -160 |
| 1980-09-02 | @ BAL | 132 | L 4-10 | 47-85 | 7 | 7,658 | Jim Beattie | Jim Palmer | Jim Palmer | Jim Beattie | | 489 | 655 | -166 |
| 1980-09-03 | @ BAL | 133 | L 1-5 | 47-86 | 7 | 12,110 | Rob Dressler | Steve Stone | Steve Stone | Rob Dressler | | 490 | 660 | -170 |
| 1980-09-04 | @ BOS | 134 | W 7-4 | 48-86 | 7 | 18,256 | Glenn Abbott | Dennis Eckersley | Glenn Abbott | Dennis Eckersley | Manny Sarmiento | 497 | 664 | -167 |
| 1980-09-05 | @ BOS | 135 | W 4-2 | 49-86 | 7 | 20,420 | Floyd Bannister | John Tudor | Floyd Bannister | John Tudor | Shane Rawley | 501 | 666 | -165 |
| 1980-09-06 | @ BOS | 136 | L 1-5 | 49-87 | 7 | 23,317 | Mike Parrott | Dick Drago | Dick Drago | Mike Parrott | Tom Burgmeier | 502 | 671 | -169 |
| 1980-09-07 | @ BOS | 137 | W 12-6 | 50-87 | 7 | 23,360 | Rick Anderson | Steve Renko | Byron McLaughlin | Steve Renko | | 514 | 677 | -163 |
| 1980-09-08 | @ CHA | 138 | L 2-3 | 50-88 | 7 | 5,184 | Rob Dressler | Richard Dotson | Ed Farmer | Dave Heaverlo | | 516 | 680 | -164 |
| 1980-09-09 | @ CHA | 139 | W 4-1 | 51-88 | 7 | 5,247 | Rick Honeycutt | Ross Baumgarten | Rick Honeycutt | Ross Baumgarten | Byron McLaughlin | 520 | 681 | -161 |
| 1980-09-10 | @ CHA | 140 | L 3-4 | 51-89 | 7 | 3,028 | Glenn Abbott | LaMarr Hoyt | LaMarr Hoyt | Manny Sarmiento | Ed Farmer | 523 | 685 | -162 |
| 1980-09-12 | vs MIL | 141 | L 1-7 | 51-90 | 7 | 8,622 | Floyd Bannister | Moose Haas | Moose Haas | Floyd Bannister | | 524 | 692 | -168 |
| 1980-09-13 | vs MIL | 142 | L 0-8 | 51-91 | 7 | 9,618 | Mike Parrott | Mike Caldwell | Mike Caldwell | Mike Parrott | | 524 | 700 | -176 |
| 1980-09-14 | vs MIL | 143 | L 2-3 | 51-92 | 7 | 7,387 | Rick Honeycutt | Bob McClure | Bob McClure | Rick Honeycutt | Reggie Cleveland | 526 | 703 | -177 |
| 1980-09-15 | vs CHA | 144 | W 12-1 | 52-92 | 7 | 4,141 | Rob Dressler | LaMarr Hoyt | Rob Dressler | LaMarr Hoyt | | 538 | 704 | -166 |
| 1980-09-16 | vs CHA | 145 | L 1-2 | 52-93 | 7 | 5,149 | Glenn Abbott | Richard Dotson | Richard Dotson | Glenn Abbott | Ed Farmer | 539 | 706 | -167 |
| 1980-09-17 | vs CHA | 146 | W 4-0 | 53-93 | 7 | 5,435 | Floyd Bannister | Britt Burns | Floyd Bannister | Britt Burns | Mike Parrott | 543 | 706 | -163 |
| 1980-09-18 | vs CHA | 147 | L 4-5 | 53-94 | 7 | 4,293 | Jim Beattie | Steve Trout | Mike Proly | Shane Rawley | Guy Hoffman | 547 | 711 | -164 |
| 1980-09-19 | @ MIL | 148 | L 0-4 | 53-95 | 7 | 7,470 | Rick Honeycutt | Bob McClure | Bob McClure | Rick Honeycutt | | 547 | 715 | -168 |
| 1980-09-20 | @ MIL | 149 | L 4-8 | 53-96 | 7 | 23,328 | Rob Dressler | Dave LaPoint | Dave LaPoint | Rob Dressler | Bill Castro | 551 | 723 | -172 |
| 1980-09-21 | @ MIL | 150 | W 7-5 | 54-96 | 7 | 9,642 | Glenn Abbott | Paul Mitchell | Glenn Abbott | Paul Mitchell | Mike Parrott | 558 | 728 | -170 |
| 1980-09-22 | vs KCA | 151 | W 5-4 | 55-96 | 7 | 8,643 | Floyd Bannister | Larry Gura | Byron McLaughlin | Dan Quisenberry | | 563 | 732 | -169 |
| 1980-09-23 | vs KCA | 152 | W 7-3 | 56-96 | 7 | 10,879 | Jim Beattie | Renie Martin | Jim Beattie | Renie Martin | | 570 | 735 | -165 |
| 1980-09-24 | vs KCA | 153 | W 4-2 | 57-96 | 7 | 11,180 | Rick Honeycutt | Paul Splittorff | Rick Honeycutt | Paul Splittorff | Mike Parrott | 574 | 737 | -163 |
| 1980-09-25 | vs TEX | 154 | W 7-6 | 58-96 | 7 | 4,472 | Rob Dressler | Don Kainer | Dave Heaverlo | Danny Darwin | | 581 | 743 | -162 |
| 1980-09-26 | vs TEX | 155 | W 7-2 | 59-96 | 7 | 9,535 | Glenn Abbott | Fergie Jenkins | Glenn Abbott | Fergie Jenkins | | 588 | 745 | -157 |
| 1980-09-27 | vs TEX | 156 | L 3-7 | 59-97 | 7 | 12,496 | Floyd Bannister | Doc Medich | Doc Medich | Floyd Bannister | | 591 | 752 | -161 |
| 1980-09-28 | vs TEX | 157 | L 1-4 | 59-98 | 7 | 7,616 | Jim Beattie | John Butcher | John Butcher | Jim Beattie | Danny Darwin | 592 | 756 | -164 |
| 1980-09-30 | @ KCA | 158 | L 5-7 | 59-99 | 7 | 17,272 | Rick Honeycutt | Dennis Leonard | Dan Quisenberry | Mike Parrott | | 597 | 763 | -166 |
| 1980-10-01 | @ KCA | 159 | L 1-4 | 59-100 | 7 | 15,604 | Rob Dressler | Rich Gale | Marty Pattin | Rob Dressler | Ken Brett | 598 | 767 | -169 |
| 1980-10-02 | @ KCA | 160 | L 2-6 | 59-101 | 7 | 15,241 | Floyd Bannister | Renie Martin | Renie Martin | Floyd Bannister | | 600 | 773 | -173 |
| 1980-10-03 | @ TEX | 161 | L 2-6 | 59-102 | 7 | 11,226 | Glenn Abbott | Doc Medich | Doc Medich | Glenn Abbott | | 602 | 779 | -177 |
| 1980-10-04 | @ TEX | 162 | L 6-11 | 59-103 | 7 | 9,241 | Jim Beattie | John Butcher | John Butcher | Jim Beattie | Jon Matlack | 608 | 790 | -182 |
| 1980-10-05 | @ TEX | 163 | L 2-3 | 59-104 | 7 | 7,384 | Rick Anderson | Don Kainer | Danny Darwin | Mike Parrott | | 610 | 793 | -183 |