| 1980-04-10 | @ TEX | 1 | L 0-1 | 0-1 | 6 | 33,196 | Ron Guidry | Jon Matlack | Sparky Lyle | Tom Underwood | | 0 | 1 | -1 |
| 1980-04-11 | @ TEX | 2 | L 7-11 | 0-2 | 7 | 21,424 | Tommy John | Fergie Jenkins | Fergie Jenkins | Ron Davis | Dave Rajsich | 7 | 12 | -5 |
| 1980-04-13 | @ TEX | 3 | W 9-4 | 2-2 | 2 | 0 | Luis Tiant | Steve Comer | Luis Tiant | Steve Comer | | 16 | 16 | 0 |
| 1980-04-13 | @ TEX | 4 | W 8-2 | 2-2 | 2 | 13,882 | Ed Figueroa | Gaylord Perry | Ed Figueroa | Gaylord Perry | Tom Underwood | 24 | 18 | 6 |
| 1980-04-15 | @ CHA | 5 | L 3-4 | 2-3 | 4 | 6,614 | Ron Guidry | Steve Trout | Rich Wortham | Jim Kaat | | 27 | 22 | 5 |
| 1980-04-16 | @ CHA | 6 | W 6-0 | 3-3 | 4 | 9,680 | Tommy John | Ken Kravec | Tommy John | Ken Kravec | | 33 | 22 | 11 |
| 1980-04-17 | @ CHA | 7 | L 6-8 | 3-4 | 4 | 5,555 | Mike Griffin | Britt Burns | Britt Burns | Mike Griffin | Ed Farmer | 39 | 30 | 9 |
| 1980-04-18 | vs MIL | 8 | L 2-3 | 3-5 | 5 | 47,362 | Luis Tiant | Mike Caldwell | Mike Caldwell | Luis Tiant | Jerry Augustine | 41 | 33 | 8 |
| 1980-04-19 | vs MIL | 9 | L 1-5 | 3-6 | 5 | 23,132 | Ed Figueroa | Moose Haas | Moose Haas | Ed Figueroa | Bob McClure | 42 | 38 | 4 |
| 1980-04-20 | vs MIL | 10 | W 9-5 | 4-6 | 5 | 32,427 | Ron Guidry | Bill Travers | Ron Davis | Jerry Augustine | | 51 | 43 | 8 |
| 1980-04-21 | vs BAL | 11 | W 3-2 | 5-6 | 5 | 21,419 | Tommy John | Mike Flanagan | Tommy John | Mike Flanagan | Rich Gossage | 54 | 45 | 9 |
| 1980-04-22 | vs BAL | 12 | W 5-4 | 6-6 | 3 | 16,812 | Mike Griffin | Scott McGregor | Tom Underwood | Tim Stoddard | | 59 | 49 | 10 |
| 1980-04-23 | vs BAL | 13 | W 6-5 | 7-6 | 3 | 24,302 | Luis Tiant | Jim Palmer | Ron Davis | Jim Palmer | Rich Gossage | 65 | 54 | 11 |
| 1980-04-25 | vs CHA | 14 | L 0-6 | 7-7 | 2 | 17,076 | Ed Figueroa | Steve Trout | Steve Trout | Ed Figueroa | | 65 | 60 | 5 |
| 1980-04-26 | vs CHA | 15 | L 7-8 | 7-8 | 3 | 18,020 | Ron Guidry | Ken Kravec | Ed Farmer | Tom Underwood | Randy Scarbery | 72 | 68 | 4 |
| 1980-04-27 | vs CHA | 16 | W 1-0 | 8-8 | 2 | 20,431 | Tommy John | Britt Burns | Tommy John | Britt Burns | | 73 | 68 | 5 |
| 1980-04-29 | @ BAL | 17 | W 4-3 | 9-8 | 2 | 21,440 | Luis Tiant | Scott McGregor | Luis Tiant | Scott McGregor | Rudy May | 77 | 71 | 6 |
| 1980-04-30 | @ BAL | 18 | L 4-7 | 9-9 | 2 | 17,166 | Tom Underwood | Steve Stone | Steve Stone | Tom Underwood | Tim Stoddard | 81 | 78 | 3 |
| 1980-05-02 | @ MIN | 19 | W 9-6 | 10-9 | 2 | 17,067 | Ron Guidry | Geoff Zahn | Ron Guidry | Geoff Zahn | Rudy May | 90 | 84 | 6 |
| 1980-05-03 | @ MIN | 20 | W 7-3 | 11-9 | 2 | 12,054 | Tommy John | Darrell Jackson | Tommy John | Darrell Jackson | | 97 | 87 | 10 |
| 1980-05-04 | @ MIN | 21 | W 10-1 | 12-9 | 1 | 13,085 | Tom Underwood | Jerry Koosman | Tom Underwood | Jerry Koosman | | 107 | 88 | 19 |
| 1980-05-06 | @ MIL | 22 | W 6-5 | 13-9 | 1 | 17,042 | Luis Tiant | Mike Caldwell | Rudy May | Reggie Cleveland | | 113 | 93 | 20 |
| 1980-05-07 | @ MIL | 23 | W 4-1 | 14-9 | 1 | 12,790 | Tommy John | Bill Travers | Tommy John | Bill Travers | | 117 | 94 | 23 |
| 1980-05-09 | vs MIN | 24 | W 5-2 | 15-9 | 1 | 27,225 | Ron Guidry | Jerry Koosman | Ron Guidry | Jerry Koosman | Rich Gossage | 122 | 96 | 26 |
| 1980-05-10 | vs MIN | 25 | L 0-1 | 15-10 | 1 | 28,015 | Tom Underwood | Darrell Jackson | Darrell Jackson | Rudy May | Doug Corbett | 122 | 97 | 25 |
| 1980-05-11 | vs MIN | 26 | W 5-0 | 16-10 | 1 | 30,680 | Tommy John | Geoff Zahn | Tommy John | Geoff Zahn | | 127 | 97 | 30 |
| 1980-05-12 | vs KCA | 27 | L 3-12 | 16-11 | 1 | 17,010 | Luis Tiant | Larry Gura | Larry Gura | Luis Tiant | Marty Pattin | 130 | 109 | 21 |
| 1980-05-13 | vs KCA | 28 | L 1-4 | 16-12 | 2 | 20,107 | Mike Griffin | Renie Martin | Renie Martin | Mike Griffin | Dan Quisenberry | 131 | 113 | 18 |
| 1980-05-14 | vs KCA | 29 | W 16-3 | 17-12 | 1 | 21,953 | Ron Guidry | Dennis Leonard | Ron Guidry | Dennis Leonard | Ed Figueroa | 147 | 116 | 31 |
| 1980-05-16 | vs TEX | 30 | W 6-2 | 18-12 | 1 | 30,068 | Tommy John | Doc Medich | Tommy John | Doc Medich | | 153 | 118 | 35 |
| 1980-05-17 | vs TEX | 31 | W 3-0 | 19-12 | 1 | 28,173 | Tom Underwood | Jon Matlack | Tom Underwood | Jon Matlack | | 156 | 118 | 38 |
| 1980-05-18 | vs TEX | 32 | L 4-5 | 19-13 | 1 | 48,030 | Mike Griffin | Fergie Jenkins | Sparky Lyle | Ron Davis | | 160 | 123 | 37 |
| 1980-05-19 | @ DET | 33 | W 1-0 | 20-13 | 1 | 27,715 | Ron Guidry | Milt Wilcox | Ron Guidry | Milt Wilcox | | 161 | 123 | 38 |
| 1980-05-20 | @ DET | 34 | L 8-12 | 20-14 | 1 | 31,194 | Tommy John | Pat Underwood | John Hiller | Tommy John | Dave Rozema | 169 | 135 | 34 |
| 1980-05-21 | @ DET | 35 | W 9-5 | 21-14 | 1 | 32,478 | Tom Underwood | Dan Schatzeder | Rudy May | Aurelio Lopez | | 178 | 140 | 38 |
| 1980-05-22 | @ TOR | 36 | W 5-1 | 22-14 | 1 | 26,047 | Mike Griffin | Dave Stieb | Mike Griffin | Dave Stieb | | 183 | 141 | 42 |
| 1980-05-23 | @ TOR | 37 | W 7-3 | 23-14 | 1 | 24,585 | Ron Guidry | Paul Mirabella | Ron Guidry | Paul Mirabella | | 190 | 144 | 46 |
| 1980-05-24 | @ TOR | 38 | W 6-2 | 24-14 | 1 | 31,021 | Luis Tiant | Jim Clancy | Luis Tiant | Jim Clancy | Rudy May | 196 | 146 | 50 |
| 1980-05-25 | @ TOR | 39 | L 6-9 | 24-15 | 1 | 33,077 | Tommy John | Luis Leal | Luis Leal | Tommy John | | 202 | 155 | 47 |
| 1980-05-26 | vs DET | 40 | W 13-5 | 25-15 | 1 | 28,170 | Tom Underwood | Dan Schatzeder | Tom Underwood | Dan Schatzeder | Rich Gossage | 215 | 160 | 55 |
| 1980-05-27 | vs DET | 41 | W 9-6 | 26-15 | 1 | 20,150 | Mike Griffin | Dan Petry | Mike Griffin | Dan Petry | Ron Davis | 224 | 166 | 58 |
| 1980-05-28 | vs DET | 42 | L 3-6 | 26-16 | 1 | 26,382 | Ron Guidry | Jack Morris | Jack Morris | Ron Guidry | Aurelio Lopez | 227 | 172 | 55 |
| 1980-05-30 | vs TOR | 43 | W 6-0 | 27-16 | 1 | 24,319 | Luis Tiant | Jim Clancy | Luis Tiant | Jim Clancy | Rich Gossage | 233 | 172 | 61 |
| 1980-05-31 | vs TOR | 44 | W 8-6 | 28-16 | 1 | 25,158 | Tommy John | Jesse Jefferson | Rudy May | Joey McLaughlin | | 241 | 178 | 63 |
| 1980-06-01 | vs TOR | 45 | W 11-7 | 29-16 | 1 | 52,049 | Tom Underwood | Paul Mirabella | Tom Underwood | Paul Mirabella | | 252 | 185 | 67 |
| 1980-06-02 | @ KCA | 46 | W 5-3 | 30-16 | 1 | 39,261 | Ron Guidry | Paul Splittorff | Ron Guidry | Paul Splittorff | | 257 | 188 | 69 |
| 1980-06-03 | @ KCA | 47 | L 5-6 | 30-17 | 1 | 26,734 | Mike Griffin | Larry Gura | Dan Quisenberry | Ron Davis | | 262 | 194 | 68 |
| 1980-06-04 | @ KCA | 48 | L 3-9 | 30-18 | 1 | 27,234 | Luis Tiant | Renie Martin | Renie Martin | Luis Tiant | | 265 | 203 | 62 |
| 1980-06-06 | @ SEA | 49 | W 3-0 | 31-18 | 1 | 28,156 | Tommy John | Jim Beattie | Tommy John | Jim Beattie | | 268 | 203 | 65 |
| 1980-06-07 | @ SEA | 50 | W 1-0 | 32-18 | 1 | 43,594 | Tom Underwood | Rick Honeycutt | Tom Underwood | Rick Honeycutt | Rich Gossage | 269 | 203 | 66 |
| 1980-06-08 | @ SEA | 51 | L 0-5 | 32-19 | 1 | 22,175 | Ron Guidry | Glenn Abbott | Glenn Abbott | Ron Guidry | | 269 | 208 | 61 |
| 1980-06-09 | @ CAL | 52 | W 8-7 | 33-19 | 1 | 30,126 | Mike Griffin | Alfredo Martinez | Rich Gossage | Dave Lemanczyk | | 277 | 215 | 62 |
| 1980-06-10 | @ CAL | 53 | L 4-5 | 33-20 | 1 | 38,996 | Luis Tiant | Frank Tanana | Mark Clear | Rudy May | | 281 | 220 | 61 |
| 1980-06-11 | @ CAL | 54 | W 9-7 | 34-20 | 1 | 39,593 | Tommy John | Bruce Kison | Rich Gossage | Mark Clear | | 290 | 227 | 63 |
| 1980-06-13 | @ OAK | 55 | L 3-4 | 35-21 | 1 | 0 | Ron Guidry | Brian Kingman | Brian Kingman | Ron Guidry | | 293 | 231 | 62 |
| 1980-06-13 | @ OAK | 56 | W 6-4 | 35-21 | 1 | 47,768 | Tom Underwood | Matt Keough | Ron Davis | Matt Keough | Rich Gossage | 299 | 235 | 64 |
| 1980-06-14 | @ OAK | 57 | W 2-1 | 36-21 | 1 | 26,410 | Ed Figueroa | Rick Langford | Ed Figueroa | Rick Langford | Rich Gossage | 301 | 236 | 65 |
| 1980-06-15 | @ OAK | 58 | W 8-2 | 37-21 | 1 | 47,186 | Luis Tiant | Steve McCatty | Luis Tiant | Steve McCatty | | 309 | 238 | 71 |
| 1980-06-16 | vs SEA | 59 | W 6-3 | 38-21 | 1 | 20,862 | Tommy John | Jim Beattie | Tommy John | Jim Beattie | Rich Gossage | 315 | 241 | 74 |
| 1980-06-17 | vs SEA | 60 | W 8-2 | 39-21 | 1 | 20,835 | Tom Underwood | Rick Honeycutt | Tom Underwood | Rick Honeycutt | Ron Davis | 323 | 243 | 80 |
| 1980-06-18 | vs CAL | 61 | W 5-0 | 40-21 | 1 | 30,876 | Ron Guidry | Don Aase | Ron Guidry | Don Aase | | 328 | 243 | 85 |
| 1980-06-19 | vs CAL | 62 | W 7-5 | 41-21 | 1 | 24,143 | Ed Figueroa | Alfredo Martinez | Rudy May | Dave Lemanczyk | | 335 | 248 | 87 |
| 1980-06-20 | vs OAK | 63 | W 15-7 | 42-21 | 1 | 45,935 | Luis Tiant | Steve McCatty | Luis Tiant | Steve McCatty | Ron Davis | 350 | 255 | 95 |
| 1980-06-21 | vs OAK | 64 | W 5-3 | 43-21 | 1 | 51,598 | Tommy John | Mike Norris | Tommy John | Mike Norris | Rich Gossage | 355 | 258 | 97 |
| 1980-06-22 | vs OAK | 65 | L 2-5 | 43-22 | 1 | 45,745 | Tom Underwood | Matt Keough | Matt Keough | Tom Underwood | | 357 | 263 | 94 |
| 1980-06-23 | vs BOS | 66 | L 2-7 | 43-23 | 1 | 50,139 | Ron Guidry | Dennis Eckersley | Dennis Eckersley | Ron Guidry | | 359 | 270 | 89 |
| 1980-06-24 | vs BOS | 67 | W 10-5 | 44-23 | 1 | 40,161 | Ed Figueroa | Bob Stanley | Rudy May | John Tudor | Rich Gossage | 369 | 275 | 94 |
| 1980-06-25 | vs BOS | 68 | L 3-4 | 44-24 | 1 | 46,500 | Tommy John | Steve Renko | Tom Burgmeier | Tommy John | | 372 | 279 | 93 |
| 1980-06-27 | vs CLE | 69 | L 0-2 | 44-25 | 1 | 30,421 | Rudy May | Rick Waits | Rick Waits | Rudy May | | 372 | 281 | 91 |
| 1980-06-28 | vs CLE | 70 | W 11-10 | 45-25 | 1 | 42,192 | Tom Underwood | Wayne Garland | Rich Gossage | Victor Cruz | | 383 | 291 | 92 |
| 1980-06-29 | vs CLE | 71 | W 7-2 | 46-25 | 1 | 53,231 | Ron Guidry | Len Barker | Ron Guidry | Len Barker | Ron Davis | 390 | 293 | 97 |
| 1980-06-30 | @ BOS | 72 | W 6-3 | 47-25 | 1 | 33,858 | Tommy John | Bob Stanley | Tommy John | Bob Stanley | Rich Gossage | 396 | 296 | 100 |
| 1980-07-01 | @ BOS | 73 | W 3-2 | 48-25 | 1 | 35,026 | Ed Figueroa | Dennis Eckersley | Ed Figueroa | Dennis Eckersley | Ron Davis | 399 | 298 | 101 |
| 1980-07-02 | @ BOS | 74 | W 6-0 | 49-25 | 1 | 33,971 | Rudy May | Steve Renko | Rudy May | Steve Renko | | 405 | 298 | 107 |
| 1980-07-03 | @ CLE | 75 | L 0-7 | 49-26 | 1 | 73,096 | Tom Underwood | Wayne Garland | Wayne Garland | Tom Underwood | | 405 | 305 | 100 |
| 1980-07-04 | @ CLE | 76 | W 11-5 | 50-26 | 1 | 21,312 | Ron Guidry | Len Barker | Ron Guidry | Len Barker | | 416 | 310 | 106 |
| 1980-07-05 | @ CLE | 77 | W 3-2 | 51-26 | 1 | 36,614 | Tommy John | Dan Spillner | Tommy John | Dan Spillner | Rich Gossage | 419 | 312 | 107 |
| 1980-07-06 | @ CLE | 78 | L 3-5 | 51-27 | 1 | 43,209 | Ed Figueroa | Rick Waits | Rick Waits | Ed Figueroa | Sid Monge | 422 | 317 | 105 |
| 1980-07-10 | @ TEX | 79 | W 13-5 | 52-27 | 1 | 34,463 | Ron Guidry | Fergie Jenkins | Ron Guidry | Fergie Jenkins | Tim Lollar | 435 | 322 | 113 |
| 1980-07-11 | @ TEX | 80 | L 8-10 | 52-28 | 1 | 32,378 | Tom Underwood | Jon Matlack | Jon Matlack | Tom Underwood | John Henry Johnson | 443 | 332 | 111 |
| 1980-07-12 | @ CHA | 81 | W 8-0 | 53-28 | 1 | 34,308 | Tommy John | Ross Baumgarten | Tommy John | Ross Baumgarten | | 451 | 332 | 119 |
| 1980-07-13 | @ CHA | 82 | W 3-1 | 54-28 | 1 | 28,984 | Rudy May | Steve Trout | Rudy May | Steve Trout | | 454 | 333 | 121 |
| 1980-07-14 | @ CHA | 83 | W 7-6 | 55-28 | 1 | 25,185 | Ed Figueroa | Rich Wortham | Ron Davis | Ed Farmer | Rich Gossage | 461 | 339 | 122 |
| 1980-07-15 | vs MIN | 84 | L 4-5 | 55-29 | 1 | 30,747 | Ron Guidry | Jerry Koosman | Jerry Koosman | Ron Guidry | Doug Corbett | 465 | 344 | 121 |
| 1980-07-16 | vs MIN | 85 | W 11-1 | 56-29 | 1 | 28,005 | Tom Underwood | Darrell Jackson | Tom Underwood | Darrell Jackson | | 476 | 345 | 131 |
| 1980-07-17 | vs MIN | 86 | W 10-3 | 57-29 | 1 | 25,035 | Tommy John | Geoff Zahn | Tommy John | Geoff Zahn | | 486 | 348 | 138 |
| 1980-07-18 | vs KCA | 87 | L 1-13 | 57-30 | 1 | 44,170 | Rudy May | Larry Gura | Larry Gura | Rudy May | | 487 | 361 | 126 |
| 1980-07-19 | vs KCA | 88 | W 13-7 | 58-30 | 1 | 53,583 | Doug Bird | Paul Splittorff | Doug Bird | Paul Splittorff | Ron Davis | 500 | 368 | 132 |
| 1980-07-20 | vs KCA | 89 | L 3-14 | 58-31 | 1 | 50,328 | Ron Guidry | Rich Gale | Rich Gale | Ron Guidry | Dan Quisenberry | 503 | 382 | 121 |
| 1980-07-21 | vs MIL | 90 | L 4-7 | 58-32 | 1 | 32,097 | Tom Underwood | Mike Caldwell | Mike Caldwell | Tom Underwood | Bob McClure | 507 | 389 | 118 |
| 1980-07-22 | vs MIL | 91 | W 3-0 | 59-33 | 1 | 0 | Tommy John | Lary Sorensen | Tommy John | Lary Sorensen | | 510 | 389 | 121 |
| 1980-07-22 | vs MIL | 92 | L 1-4 | 59-33 | 1 | 53,668 | Rudy May | Bill Travers | Paul Mitchell | Rudy May | | 511 | 393 | 118 |
| 1980-07-23 | vs MIL | 93 | W 4-0 | 60-33 | 1 | 41,015 | Ron Guidry | Moose Haas | Ron Guidry | Moose Haas | | 515 | 393 | 122 |
| 1980-07-25 | @ KCA | 94 | L 1-6 | 60-34 | 1 | 40,039 | Luis Tiant | Rich Gale | Rich Gale | Luis Tiant | | 516 | 399 | 117 |
| 1980-07-26 | @ KCA | 95 | W 5-4 | 61-34 | 1 | 41,860 | Tom Underwood | Dennis Leonard | Rich Gossage | Dennis Leonard | | 521 | 403 | 118 |
| 1980-07-27 | @ KCA | 96 | L 0-8 | 61-35 | 1 | 40,057 | Tommy John | Larry Gura | Larry Gura | Tommy John | | 521 | 411 | 110 |
| 1980-07-28 | @ MIN | 97 | W 7-6 | 62-35 | 1 | 23,182 | Rudy May | Darrell Jackson | Doug Bird | John Verhoeven | | 528 | 417 | 111 |
| 1980-07-29 | @ MIN | 98 | L 2-3 | 62-36 | 1 | 26,501 | Luis Tiant | Geoff Zahn | Geoff Zahn | Luis Tiant | | 530 | 420 | 110 |
| 1980-07-30 | @ MIN | 99 | L 1-2 | 62-37 | 1 | 27,020 | Tom Underwood | Jerry Koosman | Jerry Koosman | Rich Gossage | | 531 | 422 | 109 |
| 1980-07-31 | @ MIL | 100 | W 7-6 | 63-37 | 1 | 43,308 | Tommy John | Mike Caldwell | Rich Gossage | John Flinn | | 538 | 428 | 110 |
| 1980-08-01 | @ MIL | 101 | W 9-4 | 64-37 | 1 | 48,317 | Ron Guidry | Bill Travers | Ron Guidry | Bill Travers | | 547 | 432 | 115 |
| 1980-08-02 | @ MIL | 102 | W 5-3 | 65-37 | 1 | 52,283 | Rudy May | Paul Mitchell | Rudy May | Paul Mitchell | Rich Gossage | 552 | 435 | 117 |
| 1980-08-03 | @ MIL | 103 | L 0-2 | 65-38 | 1 | 51,749 | Luis Tiant | Moose Haas | Moose Haas | Luis Tiant | | 552 | 437 | 115 |
| 1980-08-04 | vs TEX | 104 | W 10-4 | 66-38 | 1 | 28,603 | Tom Underwood | Gaylord Perry | Tom Underwood | Gaylord Perry | Tim Lollar | 562 | 441 | 121 |
| 1980-08-05 | vs TEX | 105 | L 1-8 | 66-39 | 1 | 38,337 | Tommy John | Fergie Jenkins | Fergie Jenkins | Tommy John | | 563 | 449 | 114 |
| 1980-08-06 | vs TEX | 106 | W 2-1 | 67-39 | 1 | 34,746 | Rudy May | Doc Medich | Rudy May | Doc Medich | Rich Gossage | 565 | 450 | 115 |
| 1980-08-08 | vs BAL | 107 | L 2-5 | 67-40 | 1 | 54,130 | Ron Guidry | Jim Palmer | Jim Palmer | Ron Guidry | Tim Stoddard | 567 | 455 | 112 |
| 1980-08-09 | vs BAL | 108 | L 2-4 | 67-41 | 1 | 48,109 | Tom Underwood | Steve Stone | Steve Stone | Tom Underwood | | 569 | 459 | 110 |
| 1980-08-10 | vs BAL | 109 | L 5-6 | 67-42 | 1 | 54,123 | Tommy John | Mike Flanagan | Tim Stoddard | Tommy John | | 574 | 465 | 109 |
| 1980-08-11 | vs CHA | 110 | W 3-1 | 68-42 | 1 | 28,292 | Rudy May | Britt Burns | Rudy May | Britt Burns | | 577 | 466 | 111 |
| 1980-08-12 | vs CHA | 111 | W 8-4 | 69-42 | 1 | 27,883 | Luis Tiant | Steve Trout | Doug Bird | Ed Farmer | | 585 | 470 | 115 |
| 1980-08-13 | vs CHA | 112 | L 1-4 | 69-43 | 1 | 33,775 | Ron Guidry | Richard Dotson | Richard Dotson | Ron Guidry | | 586 | 474 | 112 |
| 1980-08-14 | @ BAL | 113 | L 1-6 | 69-44 | 1 | 49,952 | Tom Underwood | Steve Stone | Steve Stone | Tom Underwood | | 587 | 480 | 107 |
| 1980-08-15 | @ BAL | 114 | W 4-3 | 70-44 | 1 | 50,434 | Tommy John | Mike Flanagan | Tommy John | Mike Flanagan | Rich Gossage | 591 | 483 | 108 |
| 1980-08-16 | @ BAL | 115 | W 4-1 | 71-44 | 1 | 51,649 | Gaylord Perry | Dennis Martinez | Gaylord Perry | Dennis Martinez | Rich Gossage | 595 | 484 | 111 |
| 1980-08-17 | @ BAL | 116 | L 0-1 | 71-45 | 1 | 50,073 | Luis Tiant | Scott McGregor | Scott McGregor | Luis Tiant | | 595 | 485 | 110 |
| 1980-08-18 | @ BAL | 117 | L 5-6 | 71-46 | 1 | 51,528 | Ron Guidry | Jim Palmer | Jim Palmer | Ron Guidry | Tim Stoddard | 600 | 491 | 109 |
| 1980-08-19 | @ SEA | 118 | W 3-1 | 72-46 | 1 | 15,043 | Tom Underwood | Rick Honeycutt | Tom Underwood | Rick Honeycutt | Rich Gossage | 603 | 492 | 111 |
| 1980-08-20 | @ SEA | 119 | W 6-4 | 73-46 | 1 | 14,143 | Tommy John | Glenn Abbott | Tommy John | Glenn Abbott | Rich Gossage | 609 | 496 | 113 |
| 1980-08-21 | @ SEA | 120 | L 4-6 | 73-47 | 1 | 16,400 | Gaylord Perry | Floyd Bannister | Dave Roberts | Gaylord Perry | Shane Rawley | 613 | 502 | 111 |
| 1980-08-22 | @ CAL | 121 | L 4-8 | 73-48 | 1 | 40,372 | Luis Tiant | Jim Barr | Don Aase | Luis Tiant | Andy Hassler | 617 | 510 | 107 |
| 1980-08-23 | @ CAL | 122 | W 5-2 | 74-48 | 1 | 38,331 | Rudy May | Dave LaRoche | Rudy May | Dave LaRoche | Rich Gossage | 622 | 512 | 110 |
| 1980-08-24 | @ CAL | 123 | W 4-2 | 75-48 | 1 | 38,606 | Tom Underwood | Alfredo Martinez | Ron Davis | Alfredo Martinez | Rich Gossage | 626 | 514 | 112 |
| 1980-08-25 | @ OAK | 124 | L 1-9 | 75-49 | 1 | 49,300 | Tommy John | Mike Norris | Mike Norris | Tommy John | | 627 | 523 | 104 |
| 1980-08-26 | @ OAK | 125 | L 1-3 | 75-50 | 1 | 32,146 | Luis Tiant | Rick Langford | Rick Langford | Luis Tiant | | 628 | 526 | 102 |
| 1980-08-28 | vs SEA | 126 | W 6-5 | 76-50 | 1 | 30,215 | Rudy May | Jim Beattie | Ron Guidry | Jim Beattie | | 634 | 531 | 103 |
| 1980-08-29 | vs SEA | 127 | W 5-1 | 77-50 | 1 | 30,005 | Tommy John | Rob Dressler | Tommy John | Rob Dressler | | 639 | 532 | 107 |
| 1980-08-30 | vs SEA | 128 | W 9-3 | 78-50 | 1 | 40,047 | Gaylord Perry | Glenn Abbott | Gaylord Perry | Glenn Abbott | | 648 | 535 | 113 |
| 1980-08-31 | vs SEA | 129 | L 0-1 | 78-51 | 1 | 43,024 | Luis Tiant | Floyd Bannister | Shane Rawley | Ron Guidry | | 648 | 536 | 112 |
| 1980-09-01 | vs OAK | 130 | W 5-0 | 79-51 | 1 | 31,103 | Tom Underwood | Rick Langford | Tom Underwood | Rick Langford | | 653 | 536 | 117 |
| 1980-09-02 | vs OAK | 131 | W 6-1 | 80-51 | 1 | 23,516 | Rudy May | Steve McCatty | Rudy May | Steve McCatty | | 659 | 537 | 122 |
| 1980-09-03 | vs OAK | 132 | W 8-3 | 81-51 | 1 | 27,091 | Tommy John | Brian Kingman | Tommy John | Brian Kingman | | 667 | 540 | 127 |
| 1980-09-04 | vs CAL | 133 | W 5-3 | 82-51 | 1 | 20,967 | Gaylord Perry | Frank Tanana | Gaylord Perry | Frank Tanana | Ron Guidry | 672 | 543 | 129 |
| 1980-09-05 | vs CAL | 134 | W 6-5 | 83-51 | 1 | 30,109 | Luis Tiant | Ralph Botting | Rich Gossage | Andy Hassler | | 678 | 548 | 130 |
| 1980-09-06 | vs CAL | 135 | W 7-4 | 84-51 | 1 | 37,781 | Tom Underwood | Dave Frost | Tom Underwood | Dave Frost | Rich Gossage | 685 | 552 | 133 |
| 1980-09-07 | vs CAL | 136 | W 4-1 | 85-51 | 1 | 38,794 | Rudy May | Jim Dorsey | Rudy May | Jim Dorsey | Rich Gossage | 689 | 553 | 136 |
| 1980-09-08 | @ TOR | 137 | W 7-4 | 86-51 | 1 | 23,020 | Tommy John | Dave Stieb | Tommy John | Dave Stieb | Rich Gossage | 696 | 557 | 139 |
| 1980-09-09 | @ TOR | 138 | L 4-6 | 86-52 | 1 | 22,471 | Gaylord Perry | Jackson Todd | Jackson Todd | Gaylord Perry | Mike Willis | 700 | 563 | 137 |
| 1980-09-10 | @ TOR | 139 | W 7-6 | 87-52 | 1 | 23,031 | Tom Underwood | Jim Clancy | Ron Davis | Jim Clancy | Rich Gossage | 707 | 569 | 138 |
| 1980-09-11 | @ BOS | 140 | W 8-5 | 88-52 | 1 | 32,979 | Luis Tiant | Dick Drago | Ron Davis | Tom Burgmeier | | 715 | 574 | 141 |
| 1980-09-12 | @ BOS | 141 | W 4-2 | 89-52 | 1 | 33,787 | Rudy May | Steve Renko | Rudy May | Steve Renko | Rich Gossage | 719 | 576 | 143 |
| 1980-09-13 | @ BOS | 142 | W 4-3 | 90-52 | 1 | 33,375 | Tommy John | Mike Torrez | Tommy John | Mike Torrez | | 723 | 579 | 144 |
| 1980-09-14 | @ BOS | 143 | W 5-3 | 91-52 | 1 | 33,296 | Gaylord Perry | Dennis Eckersley | Ron Davis | Dennis Eckersley | | 728 | 582 | 146 |
| 1980-09-16 | vs TOR | 144 | W 5-4 | 92-52 | 1 | 20,281 | Ron Guidry | Jim Clancy | Ron Guidry | Jim Clancy | Rich Gossage | 733 | 586 | 147 |
| 1980-09-17 | vs TOR | 145 | W 8-7 | 93-52 | 1 | 22,516 | Rudy May | Joey McLaughlin | Tom Underwood | Jack Kucek | | 741 | 593 | 148 |
| 1980-09-18 | vs TOR | 146 | L 1-2 | 93-53 | 1 | 20,129 | Tommy John | Luis Leal | Luis Leal | Tommy John | | 742 | 595 | 147 |
| 1980-09-19 | vs BOS | 147 | W 2-1 | 94-53 | 1 | 50,505 | Luis Tiant | Steve Renko | Luis Tiant | Steve Renko | Rich Gossage | 744 | 596 | 148 |
| 1980-09-20 | vs BOS | 148 | L 1-4 | 94-54 | 1 | 50,257 | Gaylord Perry | Dennis Eckersley | Dennis Eckersley | Gaylord Perry | | 745 | 600 | 145 |
| 1980-09-21 | vs BOS | 149 | W 3-0 | 95-54 | 1 | 54,033 | Ron Guidry | John Tudor | Ron Guidry | John Tudor | Rich Gossage | 748 | 600 | 148 |
| 1980-09-22 | vs CLE | 150 | W 4-3 | 96-54 | 1 | 16,024 | Tommy John | Len Barker | Tommy John | Len Barker | Rich Gossage | 752 | 603 | 149 |
| 1980-09-23 | vs CLE | 151 | W 5-4 | 97-54 | 1 | 24,061 | Rudy May | Wayne Garland | Ron Davis | Mike Stanton | | 757 | 607 | 150 |
| 1980-09-24 | vs CLE | 152 | W 7-3 | 98-54 | 1 | 22,159 | Luis Tiant | Bob Owchinko | Luis Tiant | Bob Owchinko | Tom Underwood | 764 | 610 | 154 |
| 1980-09-25 | vs CLE | 153 | L 0-5 | 98-55 | 1 | 21,441 | Gaylord Perry | Rick Waits | Rick Waits | Gaylord Perry | | 764 | 615 | 149 |
| 1980-09-26 | @ DET | 154 | W 7-5 | 99-55 | 1 | 30,864 | Ron Guidry | Dan Schatzeder | Ron Guidry | Dan Schatzeder | Ron Davis | 771 | 620 | 151 |
| 1980-09-27 | @ DET | 155 | L 1-5 | 99-56 | 1 | 27,318 | Tommy John | Jack Morris | Jack Morris | Tommy John | Aurelio Lopez | 772 | 625 | 147 |
| 1980-09-28 | @ DET | 156 | L 5-6 | 99-57 | 1 | 25,142 | Tom Underwood | Dan Petry | Aurelio Lopez | Mike Griffin | | 777 | 631 | 146 |
| 1980-09-30 | @ CLE | 157 | L 9-12 | 99-58 | 1 | 11,919 | Luis Tiant | Rick Waits | Sid Monge | Rich Gossage | Sandy Wihtol | 786 | 643 | 143 |
| 1980-10-01 | @ CLE | 158 | W 18-7 | 100-58 | 1 | 19,037 | Tommy John | Len Barker | Gaylord Perry | Len Barker | | 804 | 650 | 154 |
| 1980-10-02 | vs DET | 159 | W 3-2 | 101-58 | 1 | 24,316 | Ron Guidry | Jack Morris | Ron Guidry | Jack Morris | Rich Gossage | 807 | 652 | 155 |
| 1980-10-04 | vs DET | 160 | W 5-2 | 102-59 | 1 | 0 | Rudy May | Roger Weaver | Rudy May | Roger Weaver | Rich Gossage | 812 | 654 | 158 |
| 1980-10-04 | vs DET | 161 | L 6-7 | 102-59 | 1 | 55,410 | Mike Griffin | Dave Tobik | Dave Tobik | Mike Griffin | | 818 | 661 | 157 |
| 1980-10-05 | vs DET | 162 | W 2-1 | 103-59 | 1 | 35,879 | Tim Lollar | Dan Schatzeder | Tim Lollar | Dan Schatzeder | Doug Bird | 820 | 662 | 158 |