| 1980-04-09 | @ SEA | 1 | L 6-8 | 0-1 | 7 | 22,588 | Dave Lemanczyk | Mike Parrott | Mike Parrott | Dave Lemanczyk | Dave Heaverlo | 6 | 8 | -2 |
| 1980-04-11 | @ SEA | 2 | W 10-7 | 1-1 | 4 | 6,104 | Dave Stieb | Jim Beattie | Balor Moore | Rob Dressler | | 16 | 15 | 1 |
| 1980-04-12 | @ SEA | 3 | L 2-3 | 1-2 | 5 | 6,773 | Paul Mirabella | Rick Honeycutt | Rick Honeycutt | Jerry Garvin | | 18 | 18 | 0 |
| 1980-04-13 | @ SEA | 4 | L 1-5 | 1-3 | 7 | 4,567 | Dave Lemanczyk | Floyd Bannister | Floyd Bannister | Dave Lemanczyk | | 19 | 23 | -4 |
| 1980-04-16 | vs MIL | 5 | W 11-2 | 2-3 | 5 | 12,688 | Dave Stieb | Jim Slaton | Dave Stieb | Jim Slaton | | 30 | 25 | 5 |
| 1980-04-17 | vs MIL | 6 | W 1-0 | 3-3 | 3 | 11,235 | Paul Mirabella | Lary Sorensen | Paul Mirabella | Lary Sorensen | | 31 | 25 | 6 |
| 1980-04-19 | @ CLE | 7 | L 1-8 | 3-4 | 4 | 61,753 | Jim Clancy | Rick Waits | Rick Waits | Jim Clancy | | 32 | 33 | -1 |
| 1980-04-20 | @ CLE | 8 | W 5-3 | 4-4 | 4 | 11,220 | Dave Lemanczyk | John Denny | Dave Lemanczyk | John Denny | Joey McLaughlin | 37 | 36 | 1 |
| 1980-04-21 | @ KCA | 9 | W 7-1 | 5-4 | 3 | 21,117 | Dave Stieb | Rich Gale | Dave Stieb | Rich Gale | | 44 | 37 | 7 |
| 1980-04-22 | @ KCA | 10 | L 2-7 | 5-5 | 4 | 16,993 | Paul Mirabella | Paul Splittorff | Paul Splittorff | Paul Mirabella | | 46 | 44 | 2 |
| 1980-04-23 | @ KCA | 11 | L 4-7 | 5-6 | 4 | 18,855 | Jim Clancy | Dennis Leonard | Gary Christenson | Joey McLaughlin | Dan Quisenberry | 50 | 51 | -1 |
| 1980-04-25 | @ MIL | 12 | W 5-3 | 6-6 | 3 | 9,902 | Dave Lemanczyk | Lary Sorensen | Joey McLaughlin | Lary Sorensen | | 55 | 54 | 1 |
| 1980-04-26 | @ MIL | 13 | W 4-0 | 7-6 | 1 | 11,038 | Dave Stieb | Mike Caldwell | Dave Stieb | Mike Caldwell | | 59 | 54 | 5 |
| 1980-04-27 | @ MIL | 14 | W 8-2 | 8-6 | 1 | 11,099 | Paul Mirabella | Moose Haas | Paul Mirabella | Moose Haas | Balor Moore | 67 | 56 | 11 |
| 1980-04-29 | vs KCA | 15 | W 3-1 | 9-6 | 1 | 11,553 | Jim Clancy | Dennis Leonard | Jim Clancy | Dennis Leonard | | 70 | 57 | 13 |
| 1980-04-30 | vs KCA | 16 | L 0-3 | 9-7 | 1 | 14,029 | Jesse Jefferson | Larry Gura | Larry Gura | Jesse Jefferson | | 70 | 60 | 10 |
| 1980-05-01 | vs CLE | 17 | L 1-2 | 9-8 | 1 | 11,654 | Dave Lemanczyk | John Denny | John Denny | Dave Lemanczyk | Sid Monge | 71 | 62 | 9 |
| 1980-05-02 | vs CLE | 18 | L 1-6 | 9-9 | 4 | 14,292 | Dave Stieb | Len Barker | Len Barker | Dave Stieb | | 72 | 68 | 4 |
| 1980-05-03 | vs CLE | 19 | W 8-3 | 10-9 | 4 | 16,564 | Paul Mirabella | Rick Waits | Tom Buskey | Rick Waits | | 80 | 71 | 9 |
| 1980-05-04 | vs CLE | 20 | W 9-8 | 12-9 | 2 | 0 | Jim Clancy | Dan Spillner | Tom Buskey | Sid Monge | | 89 | 79 | 10 |
| 1980-05-04 | vs CLE | 21 | W 7-2 | 12-9 | 2 | 26,114 | Jesse Jefferson | Bob Owchinko | Jesse Jefferson | Bob Owchinko | Joey McLaughlin | 96 | 81 | 15 |
| 1980-05-06 | @ CAL | 22 | W 3-2 | 13-9 | 2 | 23,804 | Dave Lemanczyk | Don Aase | Dave Lemanczyk | Don Aase | Jerry Garvin | 99 | 83 | 16 |
| 1980-05-07 | @ CAL | 23 | W 7-3 | 14-9 | 2 | 21,733 | Dave Stieb | Chris Knapp | Dave Stieb | Chris Knapp | | 106 | 86 | 20 |
| 1980-05-08 | @ CAL | 24 | W 9-2 | 15-9 | 1 | 23,006 | Paul Mirabella | Dave Frost | Paul Mirabella | Dave Frost | | 115 | 88 | 27 |
| 1980-05-10 | @ OAK | 25 | L 3-4 | 15-10 | 2 | 4,925 | Jim Clancy | Rick Langford | Rick Langford | Jerry Garvin | | 118 | 92 | 26 |
| 1980-05-11 | @ OAK | 26 | L 1-12 | 15-11 | 2 | 7,843 | Dave Lemanczyk | Mike Norris | Mike Norris | Dave Lemanczyk | | 119 | 104 | 15 |
| 1980-05-14 | vs SEA | 27 | L 0-7 | 15-12 | 2 | 13,055 | Paul Mirabella | Glenn Abbott | Glenn Abbott | Paul Mirabella | | 119 | 111 | 8 |
| 1980-05-15 | vs SEA | 28 | W 1-0 | 16-12 | 2 | 11,579 | Jim Clancy | Floyd Bannister | Jim Clancy | Floyd Bannister | | 120 | 111 | 9 |
| 1980-05-16 | vs OAK | 29 | W 1-0 | 17-12 | 2 | 16,138 | Jesse Jefferson | Mike Norris | Jesse Jefferson | Mike Norris | | 121 | 111 | 10 |
| 1980-05-17 | vs OAK | 30 | L 2-4 | 17-13 | 2 | 23,074 | Dave Stieb | Matt Keough | Matt Keough | Joey McLaughlin | | 123 | 115 | 8 |
| 1980-05-18 | vs OAK | 31 | W 12-1 | 18-13 | 2 | 14,414 | Paul Mirabella | Rick Langford | Paul Mirabella | Rick Langford | | 135 | 116 | 19 |
| 1980-05-19 | vs BOS | 32 | W 7-2 | 19-13 | 2 | 32,731 | Jim Clancy | Jack Billingham | Jim Clancy | Jack Billingham | | 142 | 118 | 24 |
| 1980-05-20 | vs BOS | 33 | L 3-4 | 19-14 | 2 | 18,167 | Dave Lemanczyk | Chuck Rainey | Chuck Rainey | Dave Lemanczyk | Tom Burgmeier | 145 | 122 | 23 |
| 1980-05-21 | vs BOS | 34 | L 2-11 | 19-15 | 2 | 19,556 | Jesse Jefferson | Mike Torrez | Mike Torrez | Jesse Jefferson | | 147 | 133 | 14 |
| 1980-05-22 | vs NYA | 35 | L 1-5 | 19-16 | 2 | 26,047 | Dave Stieb | Mike Griffin | Mike Griffin | Dave Stieb | | 148 | 138 | 10 |
| 1980-05-23 | vs NYA | 36 | L 3-7 | 19-17 | 2 | 24,585 | Paul Mirabella | Ron Guidry | Ron Guidry | Paul Mirabella | | 151 | 145 | 6 |
| 1980-05-24 | vs NYA | 37 | L 2-6 | 19-18 | 2 | 31,021 | Jim Clancy | Luis Tiant | Luis Tiant | Jim Clancy | Rudy May | 153 | 151 | 2 |
| 1980-05-25 | vs NYA | 38 | W 9-6 | 20-18 | 2 | 33,077 | Luis Leal | Tommy John | Luis Leal | Tommy John | | 162 | 157 | 5 |
| 1980-05-26 | @ BOS | 39 | W 3-1 | 21-18 | 2 | 18,853 | Jesse Jefferson | Mike Torrez | Jerry Garvin | Dick Drago | | 165 | 158 | 7 |
| 1980-05-27 | @ BOS | 40 | L 4-5 | 21-19 | 3 | 16,679 | Paul Mirabella | Steve Renko | Steve Renko | Tom Buskey | | 169 | 163 | 6 |
| 1980-05-28 | @ BOS | 41 | W 4-1 | 22-19 | 3 | 18,215 | Dave Stieb | Bob Stanley | Dave Stieb | Bob Stanley | Joey McLaughlin | 173 | 164 | 9 |
| 1980-05-30 | @ NYA | 42 | L 0-6 | 22-20 | 3 | 24,319 | Jim Clancy | Luis Tiant | Luis Tiant | Jim Clancy | Rich Gossage | 173 | 170 | 3 |
| 1980-05-31 | @ NYA | 43 | L 6-8 | 22-21 | 3 | 25,158 | Jesse Jefferson | Tommy John | Rudy May | Joey McLaughlin | | 179 | 178 | 1 |
| 1980-06-01 | @ NYA | 44 | L 7-11 | 22-22 | 3 | 52,049 | Paul Mirabella | Tom Underwood | Tom Underwood | Paul Mirabella | | 186 | 189 | -3 |
| 1980-06-02 | vs CAL | 45 | L 3-6 | 22-23 | 5 | 15,079 | Luis Leal | Dave Frost | Dave Frost | Luis Leal | Dave LaRoche | 189 | 195 | -6 |
| 1980-06-03 | vs CAL | 46 | W 7-6 | 23-23 | 3 | 15,589 | Dave Stieb | Don Aase | Joey McLaughlin | Dave LaRoche | | 196 | 201 | -5 |
| 1980-06-04 | vs CAL | 47 | W 8-2 | 24-23 | 3 | 16,677 | Jim Clancy | Alfredo Martinez | Jim Clancy | Alfredo Martinez | | 204 | 203 | 1 |
| 1980-06-06 | @ MIN | 48 | L 0-5 | 24-24 | 3 | 5,495 | Paul Mirabella | Geoff Zahn | Geoff Zahn | Paul Mirabella | | 204 | 208 | -4 |
| 1980-06-07 | @ MIN | 49 | L 2-3 | 24-25 | 5 | 5,375 | Dave Stieb | Darrell Jackson | Darrell Jackson | Dave Stieb | Doug Corbett | 206 | 211 | -5 |
| 1980-06-08 | @ MIN | 50 | L 1-5 | 25-26 | 6 | 0 | Jesse Jefferson | Roger Erickson | Roger Erickson | Jesse Jefferson | Doug Corbett | 207 | 216 | -9 |
| 1980-06-08 | @ MIN | 51 | W 6-4 | 25-26 | 6 | 17,869 | Luis Leal | Jerry Koosman | Joey McLaughlin | Fernando Arroyo | | 213 | 220 | -7 |
| 1980-06-10 | @ CHA | 52 | W 1-0 | 26-26 | 4 | 18,225 | Jim Clancy | Ross Baumgarten | Jim Clancy | Ross Baumgarten | | 214 | 220 | -6 |
| 1980-06-11 | @ CHA | 53 | L 4-7 | 26-27 | 6 | 17,537 | Paul Mirabella | Ken Kravec | Ken Kravec | Paul Mirabella | Ed Farmer | 218 | 227 | -9 |
| 1980-06-13 | vs TEX | 54 | L 3-6 | 26-28 | 7 | 20,034 | Dave Stieb | Doc Medich | Doc Medich | Dave Stieb | Sparky Lyle | 221 | 233 | -12 |
| 1980-06-14 | vs TEX | 55 | W 7-6 | 27-28 | 6 | 24,184 | Luis Leal | Brian Allard | Tom Buskey | Bob Babcock | | 228 | 239 | -11 |
| 1980-06-15 | vs TEX | 56 | W 5-3 | 28-28 | 5 | 30,143 | Jim Clancy | Fergie Jenkins | Jim Clancy | Fergie Jenkins | Jerry Garvin | 233 | 242 | -9 |
| 1980-06-16 | vs MIN | 57 | L 0-4 | 28-29 | 7 | 14,691 | Jesse Jefferson | Geoff Zahn | Geoff Zahn | Jesse Jefferson | | 233 | 246 | -13 |
| 1980-06-17 | vs MIN | 58 | L 6-8 | 28-30 | 7 | 15,229 | Paul Mirabella | Pete Redfern | Doug Corbett | Paul Mirabella | | 239 | 254 | -15 |
| 1980-06-18 | vs CHA | 59 | W 5-4 | 30-30 | 7 | 0 | Dave Stieb | Steve Trout | Dave Stieb | Steve Trout | | 244 | 258 | -14 |
| 1980-06-18 | vs CHA | 60 | W 3-1 | 30-30 | 7 | 21,443 | Jack Kucek | Richard Dotson | Jack Kucek | Richard Dotson | Joey McLaughlin | 247 | 259 | -12 |
| 1980-06-20 | @ TEX | 61 | L 2-5 | 30-31 | 7 | 13,747 | Jim Clancy | Fergie Jenkins | Fergie Jenkins | Jerry Garvin | | 249 | 264 | -15 |
| 1980-06-21 | @ TEX | 62 | L 1-2 | 30-32 | 7 | 17,846 | Jesse Jefferson | Jon Matlack | Jon Matlack | Joey McLaughlin | | 250 | 266 | -16 |
| 1980-06-22 | @ TEX | 63 | W 6-5 | 31-32 | 7 | 13,650 | Jack Kucek | Gaylord Perry | Jerry Garvin | Jim Kern | | 256 | 271 | -15 |
| 1980-06-24 | @ BAL | 64 | L 0-1 | 31-33 | 7 | 14,884 | Dave Stieb | Scott McGregor | Scott McGregor | Dave Stieb | | 256 | 272 | -16 |
| 1980-06-25 | @ BAL | 65 | L 3-6 | 31-34 | 7 | 14,588 | Luis Leal | Jim Palmer | Jim Palmer | Luis Leal | | 259 | 278 | -19 |
| 1980-06-26 | @ BAL | 66 | L 1-4 | 31-35 | 7 | 13,023 | Jim Clancy | Steve Stone | Steve Stone | Jim Clancy | | 260 | 282 | -22 |
| 1980-06-27 | vs DET | 67 | L 2-7 | 31-36 | 7 | 18,494 | Jesse Jefferson | Jack Morris | Jack Morris | Jesse Jefferson | | 262 | 289 | -27 |
| 1980-06-28 | vs DET | 68 | L 3-8 | 31-37 | 7 | 20,059 | Jack Kucek | Dave Rozema | Dave Rozema | Jack Kucek | | 265 | 297 | -32 |
| 1980-06-29 | vs DET | 69 | W 2-0 | 32-37 | 7 | 22,026 | Dave Stieb | Dan Petry | Dave Stieb | Dan Petry | | 267 | 297 | -30 |
| 1980-06-30 | vs BAL | 70 | L 7-9 | 32-38 | 7 | 18,399 | Luis Leal | Steve Stone | Steve Stone | Luis Leal | | 274 | 306 | -32 |
| 1980-07-01 | vs BAL | 71 | L 0-2 | 32-39 | 7 | 23,475 | Jim Clancy | Jim Palmer | Jim Palmer | Jim Clancy | Tippy Martinez | 274 | 308 | -34 |
| 1980-07-02 | vs BAL | 72 | L 2-6 | 32-40 | 7 | 18,461 | Paul Mirabella | Mike Flanagan | Mike Flanagan | Paul Mirabella | | 276 | 314 | -38 |
| 1980-07-03 | @ DET | 73 | L 5-8 | 32-41 | 7 | 30,027 | Jack Kucek | Dave Rozema | Pat Underwood | Joey McLaughlin | | 281 | 322 | -41 |
| 1980-07-04 | @ DET | 74 | L 3-4 | 32-42 | 7 | 29,370 | Dave Stieb | Dan Petry | Dan Petry | Dave Stieb | Aurelio Lopez | 284 | 326 | -42 |
| 1980-07-05 | @ DET | 75 | W 5-3 | 33-42 | 7 | 32,925 | Jim Clancy | Milt Wilcox | Jim Clancy | Milt Wilcox | Jerry Garvin | 289 | 329 | -40 |
| 1980-07-06 | @ DET | 76 | L 5-7 | 33-43 | 7 | 28,564 | Joey McLaughlin | Jack Morris | Jack Morris | Jerry Garvin | Aurelio Lopez | 294 | 336 | -42 |
| 1980-07-10 | vs CLE | 77 | L 3-7 | 33-44 | 7 | 17,178 | Jim Clancy | John Denny | John Denny | Jim Clancy | | 297 | 343 | -46 |
| 1980-07-11 | vs CLE | 78 | W 6-3 | 34-44 | 7 | 16,621 | Dave Stieb | Wayne Garland | Dave Stieb | Wayne Garland | | 303 | 346 | -43 |
| 1980-07-12 | vs MIL | 79 | L 2-9 | 34-45 | 7 | 23,624 | Balor Moore | Bill Travers | Bill Travers | Balor Moore | | 305 | 355 | -50 |
| 1980-07-13 | vs MIL | 80 | W 4-1 | 35-46 | 7 | 0 | Jack Kucek | Moose Haas | Jack Kucek | Moose Haas | Jerry Garvin | 309 | 356 | -47 |
| 1980-07-13 | vs MIL | 81 | L 0-4 | 35-46 | 7 | 26,331 | Joey McLaughlin | Paul Mitchell | Paul Mitchell | Joey McLaughlin | | 309 | 360 | -51 |
| 1980-07-14 | vs MIL | 82 | L 4-6 | 35-47 | 7 | 19,443 | Jim Clancy | Lary Sorensen | Jerry Augustine | Jim Clancy | Bill Castro | 313 | 366 | -53 |
| 1980-07-16 | @ SEA | 83 | W 5-0 | 36-47 | 7 | 5,644 | Dave Stieb | Glenn Abbott | Dave Stieb | Glenn Abbott | | 318 | 366 | -48 |
| 1980-07-17 | @ SEA | 84 | L 3-5 | 36-48 | 7 | 5,726 | Paul Mirabella | Floyd Bannister | Shane Rawley | Jesse Jefferson | | 321 | 371 | -50 |
| 1980-07-18 | @ CAL | 85 | L 3-6 | 36-49 | 7 | 23,866 | Jack Kucek | Ed Halicki | Ed Halicki | Jack Kucek | Mark Clear | 324 | 377 | -53 |
| 1980-07-19 | @ CAL | 86 | W 5-4 | 37-49 | 7 | 35,221 | Jim Clancy | Alfredo Martinez | Jim Clancy | John Montague | | 329 | 381 | -52 |
| 1980-07-20 | @ CAL | 87 | W 6-3 | 38-49 | 7 | 23,903 | Balor Moore | Frank Tanana | Joey McLaughlin | Mark Clear | | 335 | 384 | -49 |
| 1980-07-21 | @ OAK | 88 | W 1-0 | 39-49 | 7 | 14,588 | Dave Stieb | Brian Kingman | Dave Stieb | Brian Kingman | | 336 | 384 | -48 |
| 1980-07-22 | @ OAK | 89 | W 6-2 | 40-50 | 7 | 0 | Jesse Jefferson | Matt Keough | Jesse Jefferson | Matt Keough | Jerry Garvin | 342 | 386 | -44 |
| 1980-07-22 | @ OAK | 90 | L 1-5 | 40-50 | 7 | 8,645 | Paul Mirabella | Mike Norris | Mike Norris | Paul Mirabella | | 343 | 391 | -48 |
| 1980-07-23 | @ OAK | 91 | L 2-6 | 40-51 | 7 | 4,765 | Jack Kucek | Steve McCatty | Steve McCatty | Jack Kucek | | 345 | 397 | -52 |
| 1980-07-25 | vs SEA | 92 | W 5-3 | 41-51 | 7 | 16,248 | Jim Clancy | Rick Honeycutt | Jim Clancy | Rick Honeycutt | | 350 | 400 | -50 |
| 1980-07-26 | vs SEA | 93 | L 2-7 | 42-52 | 7 | 0 | Dave Stieb | Rob Dressler | Rob Dressler | Dave Stieb | | 352 | 407 | -55 |
| 1980-07-26 | vs SEA | 94 | W 7-5 | 42-52 | 7 | 18,067 | Balor Moore | Glenn Abbott | Jack Kucek | Glenn Abbott | Jerry Garvin | 359 | 412 | -53 |
| 1980-07-27 | vs SEA | 95 | W 5-0 | 43-52 | 7 | 17,080 | Jesse Jefferson | Floyd Bannister | Jesse Jefferson | Floyd Bannister | | 364 | 412 | -48 |
| 1980-07-28 | vs OAK | 96 | L 3-5 | 43-53 | 7 | 14,457 | Paul Mirabella | Mike Norris | Mike Norris | Mike Barlow | | 367 | 417 | -50 |
| 1980-07-29 | vs OAK | 97 | L 5-6 | 43-54 | 7 | 16,704 | Jim Clancy | Steve McCatty | Bob Lacey | Jerry Garvin | | 372 | 423 | -51 |
| 1980-07-30 | vs OAK | 98 | L 1-11 | 43-55 | 7 | 17,654 | Dave Stieb | Rick Langford | Rick Langford | Dave Stieb | | 373 | 434 | -61 |
| 1980-08-01 | vs CAL | 99 | W 9-8 | 44-55 | 7 | 16,145 | Jesse Jefferson | Chris Knapp | Jerry Garvin | Mark Clear | | 382 | 442 | -60 |
| 1980-08-02 | vs CAL | 100 | L 4-5 | 44-56 | 7 | 22,051 | Mike Barlow | Dave LaRoche | Dave LaRoche | Jesse Jefferson | | 386 | 447 | -61 |
| 1980-08-03 | vs CAL | 101 | W 3-1 | 45-56 | 7 | 20,404 | Jim Clancy | Alfredo Martinez | Jim Clancy | Alfredo Martinez | Mike Barlow | 389 | 448 | -59 |
| 1980-08-04 | @ CLE | 102 | L 5-11 | 45-57 | 7 | 7,583 | Paul Mirabella | Dan Spillner | Dan Spillner | Paul Mirabella | Sid Monge | 394 | 459 | -65 |
| 1980-08-05 | @ CLE | 103 | L 5-8 | 45-58 | 7 | 6,707 | Jack Kucek | Ross Grimsley | Ross Grimsley | Jack Kucek | Victor Cruz | 399 | 467 | -68 |
| 1980-08-06 | @ CLE | 104 | L 2-5 | 45-59 | 7 | 9,098 | Jesse Jefferson | Rick Waits | Rick Waits | Jesse Jefferson | Victor Cruz | 401 | 472 | -71 |
| 1980-08-07 | @ CLE | 105 | L 6-7 | 45-60 | 7 | 9,586 | Jack Kucek | Wayne Garland | Sid Monge | Jerry Garvin | | 407 | 479 | -72 |
| 1980-08-08 | vs KCA | 106 | L 0-9 | 45-62 | 7 | 0 | Jim Clancy | Rich Gale | Rich Gale | Jim Clancy | | 407 | 488 | -81 |
| 1980-08-08 | vs KCA | 107 | L 4-7 | 45-62 | 7 | 22,146 | Jackson Todd | Paul Splittorff | Marty Pattin | Jerry Garvin | | 411 | 495 | -84 |
| 1980-08-09 | vs KCA | 108 | W 4-3 | 46-62 | 7 | 21,300 | Dave Stieb | Steve Busby | Mike Willis | Rawly Eastwick | | 415 | 498 | -83 |
| 1980-08-10 | vs KCA | 109 | L 5-8 | 46-63 | 7 | 23,473 | Jesse Jefferson | Dennis Leonard | Dennis Leonard | Jesse Jefferson | Marty Pattin | 420 | 506 | -86 |
| 1980-08-12 | @ MIL | 110 | W 3-1 | 48-63 | 7 | 0 | Jim Clancy | Lary Sorensen | Jim Clancy | Lary Sorensen | | 423 | 507 | -84 |
| 1980-08-12 | @ MIL | 111 | W 5-4 | 48-63 | 7 | 18,820 | Jack Kucek | Paul Mitchell | Mike Barlow | Bill Castro | Jerry Garvin | 428 | 511 | -83 |
| 1980-08-13 | @ MIL | 112 | L 4-5 | 48-64 | 7 | 14,304 | Jackson Todd | Bill Travers | Bill Travers | Joey McLaughlin | | 432 | 516 | -84 |
| 1980-08-14 | @ MIL | 113 | L 2-4 | 48-65 | 7 | 21,115 | Dave Stieb | Moose Haas | Moose Haas | Dave Stieb | | 434 | 520 | -86 |
| 1980-08-15 | @ KCA | 114 | L 3-4 | 48-66 | 7 | 34,861 | Jesse Jefferson | Dennis Leonard | Dennis Leonard | Jesse Jefferson | Dan Quisenberry | 437 | 524 | -87 |
| 1980-08-16 | @ KCA | 115 | L 5-11 | 48-67 | 7 | 39,631 | Jack Kucek | Larry Gura | Larry Gura | Jack Kucek | | 442 | 535 | -93 |
| 1980-08-17 | @ KCA | 116 | L 3-8 | 48-68 | 7 | 30,693 | Jim Clancy | Paul Splittorff | Paul Splittorff | Jim Clancy | Dan Quisenberry | 445 | 543 | -98 |
| 1980-08-19 | @ MIN | 117 | W 4-3 | 49-68 | 7 | 6,902 | Dave Stieb | Darrell Jackson | Mike Barlow | Doug Corbett | Ken Schrom | 449 | 546 | -97 |
| 1980-08-20 | @ MIN | 118 | W 10-4 | 50-68 | 7 | 4,198 | Jackson Todd | Geoff Zahn | Jackson Todd | Geoff Zahn | | 459 | 550 | -91 |
| 1980-08-21 | @ CHA | 119 | L 3-5 | 50-69 | 7 | 15,303 | Jesse Jefferson | LaMarr Hoyt | LaMarr Hoyt | Jesse Jefferson | Ed Farmer | 462 | 555 | -93 |
| 1980-08-22 | @ CHA | 120 | L 0-2 | 50-70 | 7 | 15,033 | Jim Clancy | Britt Burns | Britt Burns | Jim Clancy | Ed Farmer | 462 | 557 | -95 |
| 1980-08-23 | @ CHA | 121 | L 1-5 | 50-71 | 7 | 10,768 | Jack Kucek | Richard Dotson | Richard Dotson | Jack Kucek | | 463 | 562 | -99 |
| 1980-08-24 | @ CHA | 122 | W 7-3 | 51-71 | 7 | 17,156 | Dave Stieb | Ross Baumgarten | Dave Stieb | Ross Baumgarten | Mike Barlow | 470 | 565 | -95 |
| 1980-08-25 | vs TEX | 123 | L 1-5 | 51-72 | 7 | 15,517 | Jackson Todd | Ken Clay | Ken Clay | Jackson Todd | John Henry Johnson | 471 | 570 | -99 |
| 1980-08-26 | vs TEX | 124 | L 0-8 | 51-73 | 7 | 15,478 | Jesse Jefferson | Charlie Hough | Charlie Hough | Jesse Jefferson | | 471 | 578 | -107 |
| 1980-08-27 | vs TEX | 125 | W 6-4 | 52-73 | 7 | 15,442 | Jim Clancy | Doc Medich | Jim Clancy | Doc Medich | Jerry Garvin | 477 | 582 | -105 |
| 1980-08-28 | vs MIN | 126 | L 5-7 | 52-74 | 7 | 14,035 | Joey McLaughlin | Darrell Jackson | John Verhoeven | Jesse Jefferson | Albert Williams | 482 | 589 | -107 |
| 1980-08-29 | vs MIN | 127 | L 2-5 | 52-75 | 7 | 14,358 | Dave Stieb | Geoff Zahn | Geoff Zahn | Dave Stieb | | 484 | 594 | -110 |
| 1980-08-30 | vs MIN | 128 | W 3-2 | 53-75 | 7 | 18,376 | Jackson Todd | Roger Erickson | Jackson Todd | John Verhoeven | | 487 | 596 | -109 |
| 1980-08-31 | vs MIN | 129 | W 7-1 | 54-75 | 7 | 18,029 | Jim Clancy | Jerry Koosman | Jim Clancy | Jerry Koosman | | 494 | 597 | -103 |
| 1980-09-01 | @ TEX | 130 | L 1-9 | 54-76 | 7 | 8,224 | Joey McLaughlin | Doc Medich | Doc Medich | Joey McLaughlin | | 495 | 606 | -111 |
| 1980-09-02 | @ TEX | 131 | L 2-3 | 54-77 | 7 | 6,903 | Luis Leal | Fergie Jenkins | Fergie Jenkins | Luis Leal | | 497 | 609 | -112 |
| 1980-09-03 | @ TEX | 132 | W 4-2 | 55-77 | 7 | 6,984 | Dave Stieb | Ed Figueroa | Dave Stieb | Ed Figueroa | | 501 | 611 | -110 |
| 1980-09-04 | vs CHA | 133 | W 3-2 | 56-77 | 7 | 12,365 | Jackson Todd | Ross Baumgarten | Jackson Todd | Ed Farmer | | 504 | 613 | -109 |
| 1980-09-05 | vs CHA | 134 | L 0-3 | 56-78 | 7 | 14,091 | Jim Clancy | LaMarr Hoyt | LaMarr Hoyt | Jim Clancy | | 504 | 616 | -112 |
| 1980-09-07 | vs CHA | 135 | W 3-1 | 58-78 | 7 | 0 | Joey McLaughlin | Steve Trout | Joey McLaughlin | Steve Trout | Mike Barlow | 507 | 617 | -110 |
| 1980-09-07 | vs CHA | 136 | W 7-6 | 58-78 | 7 | 17,457 | Luis Leal | Britt Burns | Ken Schrom | Mike Proly | Mike Barlow | 514 | 623 | -109 |
| 1980-09-08 | vs NYA | 137 | L 4-7 | 58-79 | 7 | 23,020 | Dave Stieb | Tommy John | Tommy John | Dave Stieb | Rich Gossage | 518 | 630 | -112 |
| 1980-09-09 | vs NYA | 138 | W 6-4 | 59-79 | 7 | 22,471 | Jackson Todd | Gaylord Perry | Jackson Todd | Gaylord Perry | Mike Willis | 524 | 634 | -110 |
| 1980-09-10 | vs NYA | 139 | L 6-7 | 59-80 | 7 | 23,031 | Jim Clancy | Tom Underwood | Ron Davis | Jim Clancy | Rich Gossage | 530 | 641 | -111 |
| 1980-09-11 | vs BAL | 140 | L 1-6 | 59-81 | 7 | 14,025 | Paul Mirabella | Steve Stone | Steve Stone | Paul Mirabella | | 531 | 647 | -116 |
| 1980-09-12 | vs BAL | 141 | W 7-5 | 60-81 | 7 | 15,632 | Joey McLaughlin | Mike Flanagan | Joey McLaughlin | Mike Flanagan | Mike Willis | 538 | 652 | -114 |
| 1980-09-13 | vs BAL | 142 | L 4-6 | 60-82 | 7 | 18,043 | Dave Stieb | Scott McGregor | Scott McGregor | Dave Stieb | Tim Stoddard | 542 | 658 | -116 |
| 1980-09-14 | vs BAL | 143 | W 4-3 | 61-82 | 7 | 19,117 | Jackson Todd | Jim Palmer | Mike Barlow | Dennis Martinez | | 546 | 661 | -115 |
| 1980-09-16 | @ NYA | 144 | L 4-5 | 61-83 | 7 | 20,281 | Jim Clancy | Ron Guidry | Ron Guidry | Jim Clancy | Rich Gossage | 550 | 666 | -116 |
| 1980-09-17 | @ NYA | 145 | L 7-8 | 61-84 | 7 | 22,516 | Joey McLaughlin | Rudy May | Tom Underwood | Jack Kucek | | 557 | 674 | -117 |
| 1980-09-18 | @ NYA | 146 | W 2-1 | 62-84 | 7 | 20,129 | Luis Leal | Tommy John | Luis Leal | Tommy John | | 559 | 675 | -116 |
| 1980-09-19 | @ BAL | 147 | L 6-8 | 62-85 | 7 | 12,706 | Jackson Todd | Jim Palmer | Tippy Martinez | Mike Willis | | 565 | 683 | -118 |
| 1980-09-20 | @ BAL | 148 | L 1-6 | 62-86 | 7 | 16,269 | Dave Stieb | Steve Stone | Steve Stone | Dave Stieb | | 566 | 689 | -123 |
| 1980-09-21 | @ BAL | 149 | L 1-2 | 62-87 | 7 | 14,251 | Jim Clancy | Mike Flanagan | Mike Flanagan | Jim Clancy | Tim Stoddard | 567 | 691 | -124 |
| 1980-09-22 | @ DET | 150 | W 6-5 | 63-87 | 7 | 6,210 | Joey McLaughlin | Roger Weaver | Jerry Garvin | Roger Weaver | Mike Willis | 573 | 696 | -123 |
| 1980-09-23 | @ DET | 151 | W 9-7 | 64-87 | 7 | 6,363 | Luis Leal | Milt Wilcox | Mike Willis | Dave Rozema | Jack Kucek | 582 | 703 | -121 |
| 1980-09-24 | @ DET | 152 | L 8-9 | 64-88 | 7 | 7,129 | Jackson Todd | Mark Fidrych | Dan Petry | Jack Kucek | | 590 | 712 | -122 |
| 1980-09-26 | vs BOS | 153 | L 1-3 | 64-89 | 7 | 15,187 | Dave Stieb | Dennis Eckersley | Dennis Eckersley | Dave Stieb | | 591 | 715 | -124 |
| 1980-09-27 | vs BOS | 154 | L 3-4 | 64-90 | 7 | 21,533 | Jim Clancy | John Tudor | Bob Stanley | Jim Clancy | Tom Burgmeier | 594 | 719 | -125 |
| 1980-09-28 | vs BOS | 155 | L 3-7 | 64-91 | 7 | 32,042 | Joey McLaughlin | Steve Crawford | Steve Crawford | Joey McLaughlin | | 597 | 726 | -129 |
| 1980-09-29 | vs DET | 156 | L 2-8 | 64-92 | 7 | 12,051 | Paul Mirabella | Roger Weaver | Roger Weaver | Paul Mirabella | Aurelio Lopez | 599 | 734 | -135 |
| 1980-09-30 | vs DET | 157 | L 3-5 | 64-93 | 7 | 12,119 | Jackson Todd | Dan Schatzeder | Dan Schatzeder | Jackson Todd | | 602 | 739 | -137 |
| 1980-10-01 | vs DET | 158 | L 7-11 | 64-94 | 7 | 12,426 | Dave Stieb | Mark Fidrych | Mark Fidrych | Dave Stieb | Pat Underwood | 609 | 750 | -141 |
| 1980-10-02 | @ BOS | 159 | L 1-4 | 64-95 | 7 | 11,872 | Jim Clancy | John Tudor | John Tudor | Jim Clancy | | 610 | 754 | -144 |
| 1980-10-04 | @ BOS | 160 | W 7-6 | 66-95 | 7 | 0 | Joey McLaughlin | Steve Crawford | Luis Leal | Bob Stanley | Mike Barlow | 617 | 760 | -143 |
| 1980-10-04 | @ BOS | 161 | W 3-1 | 66-95 | 7 | 14,179 | Paul Mirabella | Dick Drago | Paul Mirabella | Dick Drago | | 620 | 761 | -141 |
| 1980-10-05 | @ BOS | 162 | W 4-1 | 67-95 | 7 | 16,562 | Jackson Todd | Keith MacWhorter | Jackson Todd | Keith MacWhorter | | 624 | 762 | -138 |