| 1980-04-10 | @ SLN | 1 | L 0-1 | 0-1 | 6 | 42,867 | Bert Blyleven | Pete Vuckovich | Pete Vuckovich | Bert Blyleven | | 0 | 1 | -1 |
| 1980-04-11 | @ SLN | 2 | W 4-3 | 1-1 | 4 | 16,998 | John Candelaria | Bob Forsch | Grant Jackson | Don Hood | | 4 | 4 | 0 |
| 1980-04-12 | @ SLN | 3 | W 7-2 | 2-1 | 3 | 15,662 | Jim Bibby | John Fulgham | Jim Bibby | John Fulgham | | 11 | 6 | 5 |
| 1980-04-13 | @ SLN | 4 | W 3-0 | 3-1 | 1 | 16,301 | Jim Rooker | Silvio Martinez | Jim Rooker | Silvio Martinez | Grant Jackson | 14 | 6 | 8 |
| 1980-04-14 | vs CHN | 5 | W 5-4 | 4-1 | 1 | 44,088 | Bert Blyleven | Rick Reuschel | Kent Tekulve | Bruce Sutter | | 19 | 10 | 9 |
| 1980-04-17 | vs SLN | 6 | L 9-12 | 4-2 | 1 | 5,233 | John Candelaria | Bob Sykes | Bob Sykes | John Candelaria | | 28 | 22 | 6 |
| 1980-04-18 | vs SLN | 7 | W 12-10 | 5-2 | 1 | 10,196 | Jim Bibby | Silvio Martinez | Grant Jackson | Darold Knowles | Kent Tekulve | 40 | 32 | 8 |
| 1980-04-19 | vs SLN | 8 | L 1-2 | 5-3 | 1 | 12,642 | Bert Blyleven | John Fulgham | John Fulgham | Dave Roberts | | 41 | 34 | 7 |
| 1980-04-20 | vs SLN | 9 | W 6-3 | 6-3 | 1 | 35,567 | Jim Rooker | Pete Vuckovich | Jim Rooker | Pete Vuckovich | Kent Tekulve | 47 | 37 | 10 |
| 1980-04-21 | @ MON | 10 | W 7-1 | 7-3 | 1 | 10,327 | John Candelaria | Ross Grimsley | John Candelaria | Ross Grimsley | | 54 | 38 | 16 |
| 1980-04-22 | @ MON | 11 | W 5-3 | 8-3 | 1 | 7,373 | Jim Bibby | Scott Sanderson | Jim Bibby | Scott Sanderson | Kent Tekulve | 59 | 41 | 18 |
| 1980-04-23 | @ MON | 12 | L 2-3 | 8-4 | 1 | 8,161 | Bert Blyleven | Steve Rogers | Steve Rogers | Bert Blyleven | | 61 | 44 | 17 |
| 1980-04-25 | @ CHN | 13 | L 3-5 | 8-5 | 2 | 7,714 | Jim Rooker | Rick Reuschel | Rick Reuschel | Jim Rooker | Bruce Sutter | 64 | 49 | 15 |
| 1980-04-26 | @ CHN | 14 | W 9-2 | 9-5 | 1 | 32,992 | John Candelaria | Dennis Lamp | John Candelaria | Dennis Lamp | | 73 | 51 | 22 |
| 1980-04-29 | vs MON | 15 | W 5-4 | 10-5 | 1 | 8,498 | Bert Blyleven | Steve Rogers | Eddie Solomon | Elias Sosa | | 78 | 55 | 23 |
| 1980-04-30 | vs MON | 16 | W 5-0 | 11-5 | 1 | 8,545 | Jim Bibby | Bill Lee | Jim Bibby | Bill Lee | | 83 | 55 | 28 |
| 1980-05-01 | vs MON | 17 | W 2-1 | 12-5 | 1 | 8,426 | John Candelaria | David Palmer | Kent Tekulve | Woodie Fryman | | 85 | 56 | 29 |
| 1980-05-02 | vs ATL | 18 | L 1-6 | 12-6 | 1 | 11,476 | Jim Rooker | Phil Niekro | Phil Niekro | Jim Rooker | | 86 | 62 | 24 |
| 1980-05-03 | vs ATL | 19 | L 1-3 | 12-7 | 2 | 34,104 | Don Robinson | Larry McWilliams | Al Hrabosky | Grant Jackson | | 87 | 65 | 22 |
| 1980-05-04 | vs ATL | 20 | W 13-4 | 13-7 | 1 | 14,358 | Jim Bibby | Tommy Boggs | Jim Bibby | Tommy Boggs | | 100 | 69 | 31 |
| 1980-05-06 | vs LAN | 21 | W 2-1 | 14-7 | 1 | 9,817 | John Candelaria | Don Sutton | Kent Tekulve | Steve Howe | | 102 | 70 | 32 |
| 1980-05-07 | vs LAN | 22 | W 7-6 | 15-7 | 1 | 11,404 | Pascual Perez | Bob Welch | Kent Tekulve | Charlie Hough | | 109 | 76 | 33 |
| 1980-05-09 | @ SDN | 23 | W 4-3 | 16-7 | 1 | 34,078 | Jim Bibby | John Curtis | Kent Tekulve | Rollie Fingers | | 113 | 79 | 34 |
| 1980-05-10 | @ SDN | 24 | W 9-5 | 17-7 | 1 | 18,168 | Don Robinson | Eric Rasmussen | Don Robinson | Eric Rasmussen | Enrique Romo | 122 | 84 | 38 |
| 1980-05-11 | @ SDN | 25 | L 0-5 | 17-8 | 1 | 22,522 | John Candelaria | Randy Jones | Randy Jones | John Candelaria | | 122 | 89 | 33 |
| 1980-05-13 | @ SFN | 26 | L 0-5 | 17-9 | 1 | 13,798 | Bert Blyleven | Vida Blue | Vida Blue | Bert Blyleven | | 122 | 94 | 28 |
| 1980-05-14 | @ SFN | 27 | W 3-2 | 18-9 | 1 | 8,734 | Jim Bibby | Bob Knepper | Jim Bibby | Bob Knepper | Kent Tekulve | 125 | 96 | 29 |
| 1980-05-15 | @ SFN | 28 | W 3-2 | 19-9 | 1 | 7,781 | Don Robinson | Ed Whitson | Enrique Romo | Tom Griffin | | 128 | 98 | 30 |
| 1980-05-16 | @ LAN | 29 | L 6-8 | 19-10 | 1 | 47,929 | John Candelaria | Jerry Reuss | Jerry Reuss | Kent Tekulve | Rick Sutcliffe | 134 | 106 | 28 |
| 1980-05-17 | @ LAN | 30 | L 1-3 | 19-11 | 1 | 50,082 | Bert Blyleven | Don Sutton | Don Sutton | Bert Blyleven | Steve Howe | 135 | 109 | 26 |
| 1980-05-18 | @ LAN | 31 | L 0-2 | 19-12 | 1 | 49,867 | Jim Bibby | Bob Welch | Bob Welch | Jim Bibby | Steve Howe | 135 | 111 | 24 |
| 1980-05-21 | vs SDN | 32 | W 4-3 | 21-12 | 1 | 0 | John Candelaria | Randy Jones | Enrique Romo | Rollie Fingers | | 139 | 114 | 25 |
| 1980-05-21 | vs SDN | 33 | W 3-2 | 21-12 | 1 | 17,301 | Don Robinson | John Curtis | Grant Jackson | John Curtis | Kent Tekulve | 142 | 116 | 26 |
| 1980-05-22 | vs SDN | 34 | L 4-6 | 21-13 | 1 | 12,496 | Bert Blyleven | Gary Lucas | Bob Shirley | Kent Tekulve | Rollie Fingers | 146 | 122 | 24 |
| 1980-05-23 | vs SFN | 35 | W 5-4 | 22-13 | 1 | 9,619 | Jim Bibby | Bob Knepper | Grant Jackson | Al Holland | | 151 | 126 | 25 |
| 1980-05-24 | vs SFN | 36 | L 9-10 | 22-14 | 1 | 11,591 | Eddie Solomon | Ed Whitson | Tom Griffin | Rod Scurry | | 160 | 136 | 24 |
| 1980-05-25 | vs SFN | 37 | L 2-5 | 22-15 | 1 | 42,626 | John Candelaria | Vida Blue | Vida Blue | John Candelaria | | 162 | 141 | 21 |
| 1980-05-26 | @ PHI | 38 | L 6-7 | 22-16 | 2 | 45,394 | Bert Blyleven | Bob Walk | Ron Reed | Kent Tekulve | | 168 | 148 | 20 |
| 1980-05-27 | @ PHI | 39 | W 3-2 | 23-16 | 1 | 35,989 | Jim Bibby | Steve Carlton | Enrique Romo | Dickie Noles | Kent Tekulve | 171 | 150 | 21 |
| 1980-05-28 | @ PHI | 40 | L 3-6 | 23-17 | 2 | 30,209 | Don Robinson | Randy Lerch | Randy Lerch | Don Robinson | Ron Reed | 174 | 156 | 18 |
| 1980-05-29 | @ PHI | 41 | W 5-4 | 24-17 | 1 | 30,630 | Eddie Solomon | Dick Ruthven | Eddie Solomon | Dick Ruthven | Enrique Romo | 179 | 160 | 19 |
| 1980-05-30 | vs NYN | 42 | L 1-5 | 24-18 | 1 | 17,101 | John Candelaria | Pat Zachry | Pat Zachry | John Candelaria | | 180 | 165 | 15 |
| 1980-05-31 | vs NYN | 43 | W 5-0 | 25-18 | 1 | 13,901 | Bert Blyleven | Craig Swan | Bert Blyleven | Craig Swan | | 185 | 165 | 20 |
| 1980-06-01 | vs NYN | 44 | W 13-3 | 26-18 | 1 | 49,626 | Jim Bibby | Pete Falcone | Jim Bibby | Pete Falcone | | 198 | 168 | 30 |
| 1980-06-02 | vs PHI | 45 | W 9-3 | 27-18 | 1 | 19,990 | Don Robinson | Randy Lerch | Don Robinson | Randy Lerch | | 207 | 171 | 36 |
| 1980-06-03 | vs PHI | 46 | W 4-3 | 28-18 | 1 | 22,141 | Eddie Solomon | Dick Ruthven | Grant Jackson | Tug McGraw | | 211 | 174 | 37 |
| 1980-06-04 | vs PHI | 47 | L 3-4 | 28-19 | 1 | 31,075 | John Candelaria | Steve Carlton | Steve Carlton | John Candelaria | | 214 | 178 | 36 |
| 1980-06-06 | @ NYN | 48 | L 4-9 | 28-20 | 1 | 18,352 | Bert Blyleven | Pete Falcone | Tom Hausman | Bert Blyleven | | 218 | 187 | 31 |
| 1980-06-07 | @ NYN | 49 | L 5-6 | 28-21 | 1 | 13,509 | Jim Bibby | John Pacella | Neil Allen | Grant Jackson | | 223 | 193 | 30 |
| 1980-06-08 | @ NYN | 50 | L 4-6 | 29-22 | 2 | 0 | Don Robinson | Ray Burris | Ray Burris | Enrique Romo | Ed Glynn | 227 | 199 | 28 |
| 1980-06-08 | @ NYN | 51 | W 3-0 | 29-22 | 2 | 29,329 | Eddie Solomon | Mark Bomback | Eddie Solomon | Mark Bomback | Kent Tekulve | 230 | 199 | 31 |
| 1980-06-10 | @ CIN | 52 | W 5-3 | 30-22 | 2 | 26,648 | John Candelaria | Mario Soto | John Candelaria | Mario Soto | Kent Tekulve | 235 | 202 | 33 |
| 1980-06-11 | @ CIN | 53 | L 2-3 | 30-23 | 2 | 29,211 | Bert Blyleven | Frank Pastore | Frank Pastore | Bert Blyleven | | 237 | 205 | 32 |
| 1980-06-12 | @ CIN | 54 | W 10-6 | 31-23 | 2 | 31,557 | Jim Bibby | Mike LaCoss | Jim Bibby | Mike LaCoss | Enrique Romo | 247 | 211 | 36 |
| 1980-06-13 | vs HOU | 55 | W 5-3 | 32-23 | 2 | 31,854 | Eddie Solomon | Joe Niekro | Eddie Solomon | Joe Niekro | Kent Tekulve | 252 | 214 | 38 |
| 1980-06-14 | vs HOU | 56 | L 3-7 | 32-24 | 2 | 33,922 | Don Robinson | Nolan Ryan | Nolan Ryan | Don Robinson | Frank LaCorte | 255 | 221 | 34 |
| 1980-06-15 | vs HOU | 57 | W 4-1 | 33-24 | 2 | 49,541 | John Candelaria | Ken Forsch | John Candelaria | Ken Forsch | | 259 | 222 | 37 |
| 1980-06-16 | vs CIN | 58 | W 5-3 | 34-24 | 1 | 19,940 | Bert Blyleven | Frank Pastore | Bert Blyleven | Frank Pastore | Grant Jackson | 264 | 225 | 39 |
| 1980-06-17 | vs CIN | 59 | L 3-4 | 34-25 | 2 | 25,565 | Jim Bibby | Mike LaCoss | Paul Moskau | Enrique Romo | | 267 | 229 | 38 |
| 1980-06-18 | @ ATL | 60 | L 2-3 | 34-27 | 3 | 0 | Eddie Solomon | Larry McWilliams | Gene Garber | Kent Tekulve | | 269 | 232 | 37 |
| 1980-06-18 | @ ATL | 61 | L 4-5 | 34-27 | 3 | 17,154 | Rick Rhoden | Phil Niekro | Rick Camp | Enrique Romo | Gene Garber | 273 | 237 | 36 |
| 1980-06-19 | @ ATL | 62 | L 3-4 | 34-28 | 3 | 10,585 | Don Robinson | Rick Matula | Rick Matula | Don Robinson | Larry Bradford | 276 | 241 | 35 |
| 1980-06-20 | @ HOU | 63 | L 4-6 | 34-29 | 3 | 35,955 | John Candelaria | Ken Forsch | Ken Forsch | John Candelaria | Joe Sambito | 280 | 247 | 33 |
| 1980-06-21 | @ HOU | 64 | L 2-4 | 34-30 | 3 | 45,867 | Bert Blyleven | Vern Ruhle | Vern Ruhle | Bert Blyleven | Joe Sambito | 282 | 251 | 31 |
| 1980-06-22 | @ HOU | 65 | W 2-1 | 35-30 | 3 | 46,213 | Jim Bibby | Joe Niekro | Jim Bibby | Joe Niekro | Grant Jackson | 284 | 252 | 32 |
| 1980-06-23 | @ SLN | 66 | L 1-6 | 35-31 | 3 | 20,422 | Eddie Solomon | Jim Kaat | Jim Kaat | Eddie Solomon | | 285 | 258 | 27 |
| 1980-06-24 | @ SLN | 67 | L 2-3 | 35-32 | 3 | 21,858 | Rick Rhoden | Bob Sykes | Bob Sykes | Rick Rhoden | | 287 | 261 | 26 |
| 1980-06-25 | @ SLN | 68 | L 1-4 | 35-33 | 3 | 26,102 | John Candelaria | Don Hood | Don Hood | John Candelaria | Kim Seaman | 288 | 265 | 23 |
| 1980-06-27 | @ MON | 69 | W 6-4 | 36-33 | 3 | 44,232 | Bert Blyleven | Steve Rogers | Enrique Romo | Steve Rogers | Don Robinson | 294 | 269 | 25 |
| 1980-06-28 | @ MON | 70 | W 4-3 | 37-33 | 2 | 38,065 | Jim Bibby | Charlie Lea | Jim Bibby | Charlie Lea | Enrique Romo | 298 | 272 | 26 |
| 1980-06-29 | @ MON | 71 | L 1-4 | 37-34 | 3 | 46,186 | Eddie Solomon | David Palmer | David Palmer | Eddie Solomon | Fred Norman | 299 | 276 | 23 |
| 1980-06-30 | vs SLN | 72 | W 5-4 | 38-34 | 3 | 16,591 | John Candelaria | Bob Sykes | Enrique Romo | Don Hood | | 304 | 280 | 24 |
| 1980-07-01 | vs SLN | 73 | W 3-2 | 39-34 | 3 | 17,006 | Bert Blyleven | Jim Kaat | Grant Jackson | Jim Kaat | | 307 | 282 | 25 |
| 1980-07-02 | vs SLN | 74 | L 5-7 | 39-35 | 3 | 15,250 | Rick Rhoden | Pete Vuckovich | John Urrea | Rod Scurry | | 312 | 289 | 23 |
| 1980-07-03 | vs CHN | 75 | W 5-3 | 40-35 | 3 | 14,062 | Jim Bibby | Mike Krukow | Jim Bibby | Mike Krukow | Grant Jackson | 317 | 292 | 25 |
| 1980-07-04 | vs CHN | 76 | L 2-4 | 40-37 | 3 | 0 | Eddie Solomon | Lynn McGlothen | Lynn McGlothen | Eddie Solomon | Bruce Sutter | 319 | 296 | 23 |
| 1980-07-04 | vs CHN | 77 | L 1-2 | 40-37 | 3 | 24,668 | Don Robinson | Doug Capilla | Doug Capilla | Don Robinson | Dick Tidrow | 320 | 298 | 22 |
| 1980-07-05 | vs CHN | 78 | W 5-4 | 41-37 | 3 | 46,372 | John Candelaria | Dennis Lamp | John Candelaria | Guillermo Hernandez | Enrique Romo | 325 | 302 | 23 |
| 1980-07-06 | vs CHN | 79 | W 5-4 | 42-37 | 3 | 25,994 | Bert Blyleven | Rick Reuschel | Jim Bibby | Dennis Lamp | | 330 | 306 | 24 |
| 1980-07-10 | @ NYN | 80 | L 0-2 | 42-38 | 3 | 21,540 | John Candelaria | Pat Zachry | Pat Zachry | John Candelaria | | 330 | 308 | 22 |
| 1980-07-11 | @ NYN | 81 | W 4-2 | 43-38 | 3 | 30,907 | Bert Blyleven | Craig Swan | Bert Blyleven | Craig Swan | Kent Tekulve | 334 | 310 | 24 |
| 1980-07-12 | @ PHI | 82 | L 4-5 | 43-39 | 3 | 53,254 | Jim Bibby | Steve Carlton | Kevin Saucier | Kent Tekulve | | 338 | 315 | 23 |
| 1980-07-13 | @ PHI | 83 | W 7-3 | 44-39 | 3 | 48,132 | Don Robinson | Nino Espinosa | Don Robinson | Nino Espinosa | Kent Tekulve | 345 | 318 | 27 |
| 1980-07-14 | @ PHI | 84 | W 13-11 | 45-39 | 3 | 44,245 | Rick Rhoden | Randy Lerch | Grant Jackson | Ron Reed | | 358 | 329 | 29 |
| 1980-07-15 | vs SFN | 85 | W 5-2 | 46-39 | 2 | 17,114 | John Candelaria | Bob Knepper | John Candelaria | Bob Knepper | Kent Tekulve | 363 | 331 | 32 |
| 1980-07-16 | vs SFN | 86 | W 3-1 | 47-39 | 2 | 18,226 | Bert Blyleven | Ed Whitson | Bert Blyleven | Ed Whitson | Grant Jackson | 366 | 332 | 34 |
| 1980-07-17 | vs SFN | 87 | W 3-2 | 48-39 | 2 | 25,508 | Jim Bibby | Bill Bordley | Kent Tekulve | Al Holland | | 369 | 334 | 35 |
| 1980-07-18 | vs LAN | 88 | W 6-4 | 49-39 | 2 | 30,131 | Rick Rhoden | Bob Welch | Rick Rhoden | Bob Welch | Enrique Romo | 375 | 338 | 37 |
| 1980-07-19 | vs LAN | 89 | W 7-3 | 50-39 | 1 | 28,731 | Don Robinson | Rick Sutcliffe | Eddie Solomon | Rick Sutcliffe | | 382 | 341 | 41 |
| 1980-07-20 | vs LAN | 90 | L 2-4 | 51-40 | 1 | 0 | John Candelaria | Burt Hooton | Burt Hooton | John Candelaria | Steve Howe | 384 | 345 | 39 |
| 1980-07-20 | vs LAN | 91 | W 8-7 | 51-40 | 1 | 41,932 | Bert Blyleven | Jerry Reuss | Grant Jackson | Bobby Castillo | | 392 | 352 | 40 |
| 1980-07-22 | @ SDN | 92 | W 4-3 | 52-40 | 1 | 17,504 | Jim Bibby | Gary Lucas | Jim Bibby | Gary Lucas | Kent Tekulve | 396 | 355 | 41 |
| 1980-07-23 | @ SDN | 93 | L 2-3 | 52-41 | 1 | 14,608 | Rick Rhoden | Rick Wise | Rollie Fingers | Enrique Romo | | 398 | 358 | 40 |
| 1980-07-24 | @ SDN | 94 | W 7-1 | 53-41 | 1 | 15,746 | Bert Blyleven | Bob Shirley | Bert Blyleven | Bob Shirley | | 405 | 359 | 46 |
| 1980-07-25 | @ SFN | 95 | W 5-1 | 54-41 | 1 | 22,830 | John Candelaria | Bob Knepper | John Candelaria | Bob Knepper | | 410 | 360 | 50 |
| 1980-07-26 | @ SFN | 96 | L 3-4 | 54-42 | 1 | 28,566 | Eddie Solomon | Alan Hargesheimer | Greg Minton | Grant Jackson | | 413 | 364 | 49 |
| 1980-07-27 | @ SFN | 97 | W 6-4 | 55-42 | 1 | 31,186 | Jim Bibby | Bill Bordley | Jim Bibby | Bill Bordley | Kent Tekulve | 419 | 368 | 51 |
| 1980-07-28 | @ LAN | 98 | W 6-4 | 56-42 | 1 | 46,973 | Rick Rhoden | Bob Welch | Rick Rhoden | Bob Welch | Kent Tekulve | 425 | 372 | 53 |
| 1980-07-29 | @ LAN | 99 | L 2-10 | 56-43 | 1 | 47,013 | Bert Blyleven | Burt Hooton | Burt Hooton | Bert Blyleven | | 427 | 382 | 45 |
| 1980-07-30 | @ LAN | 100 | L 0-3 | 56-44 | 1 | 50,308 | John Candelaria | Jerry Reuss | Jerry Reuss | John Candelaria | | 427 | 385 | 42 |
| 1980-08-01 | vs SDN | 101 | L 0-1 | 56-45 | 1 | 22,304 | Jim Bibby | Steve Mura | Steve Mura | Jim Bibby | Rollie Fingers | 427 | 386 | 41 |
| 1980-08-03 | vs SDN | 102 | L 2-5 | 56-47 | 2 | 0 | Rick Rhoden | John Curtis | John Curtis | Rick Rhoden | | 429 | 391 | 38 |
| 1980-08-03 | vs SDN | 103 | L 1-4 | 56-47 | 2 | 20,517 | Don Robinson | Bob Shirley | Bob Shirley | Don Robinson | Rollie Fingers | 430 | 395 | 35 |
| 1980-08-05 | @ CHN | 104 | L 3-11 | 56-48 | 2 | 22,939 | John Candelaria | Rick Reuschel | Rick Reuschel | John Candelaria | | 433 | 406 | 27 |
| 1980-08-06 | @ CHN | 105 | W 9-7 | 58-48 | 2 | 0 | Jim Bibby | Dennis Lamp | Kent Tekulve | Dick Tidrow | Enrique Romo | 442 | 413 | 29 |
| 1980-08-06 | @ CHN | 106 | W 2-0 | 58-48 | 2 | 24,305 | Bert Blyleven | Doug Capilla | Bert Blyleven | Doug Capilla | Grant Jackson | 444 | 413 | 31 |
| 1980-08-07 | @ CHN | 107 | W 11-3 | 59-48 | 2 | 28,364 | Eddie Solomon | Guillermo Hernandez | Eddie Solomon | Guillermo Hernandez | | 455 | 416 | 39 |
| 1980-08-08 | vs PHI | 108 | W 6-5 | 60-48 | 2 | 30,354 | Rick Rhoden | Dick Ruthven | Kent Tekulve | Tug McGraw | Enrique Romo | 461 | 421 | 40 |
| 1980-08-09 | vs PHI | 109 | W 4-1 | 61-48 | 2 | 39,984 | John Candelaria | Nino Espinosa | John Candelaria | Nino Espinosa | Kent Tekulve | 465 | 422 | 43 |
| 1980-08-10 | vs PHI | 110 | W 7-1 | 63-48 | 2 | 0 | Jim Bibby | Randy Lerch | Jim Bibby | Randy Lerch | | 472 | 423 | 49 |
| 1980-08-10 | vs PHI | 111 | W 4-1 | 63-48 | 2 | 37,323 | Don Robinson | Dan Larson | Don Robinson | Dan Larson | Kent Tekulve | 476 | 424 | 52 |
| 1980-08-11 | vs NYN | 112 | W 2-1 | 64-48 | 1 | 13,790 | Eddie Solomon | Roy Lee Jackson | Eddie Solomon | Roy Lee Jackson | | 478 | 425 | 53 |
| 1980-08-12 | vs NYN | 113 | L 1-3 | 64-49 | 2 | 18,754 | Rick Rhoden | Ray Burris | Ray Burris | Rick Rhoden | Neil Allen | 479 | 428 | 51 |
| 1980-08-13 | vs NYN | 114 | L 3-5 | 64-50 | 2 | 19,514 | John Candelaria | Pete Falcone | Tom Hausman | John Candelaria | Jeff Reardon | 482 | 433 | 49 |
| 1980-08-15 | vs MON | 115 | W 7-3 | 65-50 | 1 | 29,721 | Jim Bibby | Steve Rogers | Jim Bibby | Steve Rogers | Kent Tekulve | 489 | 436 | 53 |
| 1980-08-16 | vs MON | 116 | W 5-0 | 66-50 | 1 | 32,390 | Bert Blyleven | Scott Sanderson | Bert Blyleven | Scott Sanderson | | 494 | 436 | 58 |
| 1980-08-17 | vs MON | 117 | W 5-1 | 67-51 | 1 | 0 | Rick Rhoden | Fred Norman | Rick Rhoden | Fred Norman | | 499 | 437 | 62 |
| 1980-08-17 | vs MON | 118 | L 2-4 | 67-51 | 1 | 49,412 | Don Robinson | Bill Gullickson | Bill Gullickson | Don Robinson | Woodie Fryman | 501 | 441 | 60 |
| 1980-08-19 | @ HOU | 119 | L 2-5 | 67-52 | 1 | 39,415 | John Candelaria | Nolan Ryan | Nolan Ryan | John Candelaria | Joe Sambito | 503 | 446 | 57 |
| 1980-08-20 | @ HOU | 120 | L 1-5 | 67-53 | 1 | 32,112 | Jim Bibby | Vern Ruhle | Vern Ruhle | Jim Bibby | Dave Smith | 504 | 451 | 53 |
| 1980-08-21 | @ HOU | 121 | L 5-12 | 67-54 | 1 | 33,884 | Bert Blyleven | Joe Niekro | Joe Sambito | Bert Blyleven | | 509 | 463 | 46 |
| 1980-08-22 | @ CIN | 122 | W 4-2 | 68-54 | 1 | 37,936 | Don Robinson | Paul Moskau | Don Robinson | Paul Moskau | Kent Tekulve | 513 | 465 | 48 |
| 1980-08-23 | @ CIN | 123 | W 2-1 | 69-54 | 1 | 43,482 | Rick Rhoden | Frank Pastore | Rick Rhoden | Frank Pastore | Grant Jackson | 515 | 466 | 49 |
| 1980-08-24 | @ CIN | 124 | W 5-2 | 70-54 | 1 | 37,072 | John Candelaria | Mike LaCoss | John Candelaria | Mike LaCoss | | 520 | 468 | 52 |
| 1980-08-25 | vs ATL | 125 | L 6-8 | 70-55 | 1 | 15,657 | Jim Bibby | Larry McWilliams | Preston Hanna | Jim Bibby | Larry Bradford | 526 | 476 | 50 |
| 1980-08-26 | vs ATL | 126 | L 2-4 | 70-56 | 1 | 14,695 | Bert Blyleven | Phil Niekro | Gene Garber | Kent Tekulve | | 528 | 480 | 48 |
| 1980-08-27 | vs ATL | 127 | L 4-7 | 70-57 | 1 | 12,363 | Don Robinson | Rick Matula | Rick Matula | Don Robinson | Al Hrabosky | 532 | 487 | 45 |
| 1980-08-28 | vs CIN | 128 | L 0-4 | 70-58 | 2 | 17,406 | Rick Rhoden | Paul Moskau | Paul Moskau | Rick Rhoden | | 532 | 491 | 41 |
| 1980-08-29 | vs CIN | 129 | L 7-8 | 70-59 | 2 | 41,494 | John Candelaria | Frank Pastore | Mario Soto | Kent Tekulve | Tom Hume | 539 | 499 | 40 |
| 1980-08-30 | vs CIN | 130 | L 3-5 | 70-60 | 2 | 24,493 | Jim Bibby | Tom Seaver | Tom Seaver | Jim Bibby | | 542 | 504 | 38 |
| 1980-08-31 | vs CIN | 131 | L 4-5 | 70-61 | 1 | 21,774 | Bert Blyleven | Mike LaCoss | Mike LaCoss | Bert Blyleven | Mario Soto | 546 | 509 | 37 |
| 1980-09-01 | vs HOU | 132 | L 4-10 | 71-62 | 3 | 0 | Don Robinson | Ken Forsch | Dave Smith | Don Robinson | | 550 | 519 | 31 |
| 1980-09-01 | vs HOU | 133 | W 7-5 | 71-62 | 3 | 26,374 | Rick Rhoden | Gordie Pladson | Rick Rhoden | Gordie Pladson | Grant Jackson | 557 | 524 | 33 |
| 1980-09-03 | vs HOU | 134 | W 10-4 | 72-62 | 2 | 18,502 | John Candelaria | Joaquin Andujar | John Candelaria | Joaquin Andujar | Enrique Romo | 567 | 528 | 39 |
| 1980-09-05 | @ ATL | 135 | L 4-7 | 72-63 | 3 | 29,610 | Jim Bibby | Larry McWilliams | Rick Camp | Kent Tekulve | | 571 | 535 | 36 |
| 1980-09-06 | @ ATL | 136 | L 2-3 | 72-64 | 3 | 17,821 | Bert Blyleven | Phil Niekro | Phil Niekro | Bert Blyleven | Gene Garber | 573 | 538 | 35 |
| 1980-09-07 | @ ATL | 137 | L 5-6 | 72-65 | 3 | 19,762 | Rick Rhoden | Rick Matula | Larry Bradford | Kent Tekulve | Rick Camp | 578 | 544 | 34 |
| 1980-09-08 | @ PHI | 138 | L 2-6 | 72-66 | 3 | 40,576 | Don Robinson | Bob Walk | Tug McGraw | Enrique Romo | | 580 | 550 | 30 |
| 1980-09-09 | @ PHI | 139 | L 4-5 | 72-67 | 3 | 43,333 | John Candelaria | Steve Carlton | Warren Brusstar | Mark Lee | | 584 | 555 | 29 |
| 1980-09-10 | @ SLN | 140 | W 7-6 | 73-67 | 3 | 10,300 | Jim Bibby | Don Hood | Jim Bibby | Don Hood | Enrique Romo | 591 | 561 | 30 |
| 1980-09-11 | @ SLN | 141 | W 2-1 | 74-67 | 3 | 7,521 | Bert Blyleven | John Martin | Bert Blyleven | John Martin | | 593 | 562 | 31 |
| 1980-09-12 | @ MON | 142 | L 0-1 | 74-68 | 3 | 36,992 | Rick Rhoden | Scott Sanderson | Scott Sanderson | Rick Rhoden | | 593 | 563 | 30 |
| 1980-09-13 | @ MON | 143 | W 4-0 | 75-68 | 3 | 51,305 | Don Robinson | Steve Rogers | Don Robinson | Steve Rogers | | 597 | 563 | 34 |
| 1980-09-14 | @ MON | 144 | L 0-4 | 75-69 | 3 | 56,137 | John Candelaria | Bill Gullickson | Bill Gullickson | John Candelaria | | 597 | 567 | 30 |
| 1980-09-16 | vs PHI | 145 | W 3-2 | 76-69 | 3 | 22,239 | Jim Bibby | Dick Ruthven | Jim Bibby | Dick Ruthven | Kent Tekulve | 600 | 569 | 31 |
| 1980-09-17 | vs PHI | 146 | L 4-5 | 76-70 | 3 | 23,650 | Bert Blyleven | Steve Carlton | Tug McGraw | Kent Tekulve | Sparky Lyle | 604 | 574 | 30 |
| 1980-09-19 | vs NYN | 147 | W 4-3 | 77-70 | 3 | 17,593 | Rick Rhoden | Ed Lynch | Rick Rhoden | Ed Lynch | | 608 | 577 | 31 |
| 1980-09-20 | vs NYN | 148 | L 6-9 | 77-71 | 3 | 22,084 | Don Robinson | Pat Zachry | Neil Allen | Kent Tekulve | Dyar Miller | 614 | 586 | 28 |
| 1980-09-21 | vs NYN | 149 | W 9-4 | 78-71 | 3 | 20,320 | John Candelaria | Ray Burris | John Candelaria | Ray Burris | | 623 | 590 | 33 |
| 1980-09-22 | vs MON | 150 | W 4-2 | 79-71 | 3 | 18,416 | Jim Bibby | Scott Sanderson | Jim Bibby | Scott Sanderson | Kent Tekulve | 627 | 592 | 35 |
| 1980-09-23 | vs MON | 151 | L 1-7 | 79-72 | 3 | 26,729 | Bert Blyleven | Steve Rogers | Steve Rogers | Bert Blyleven | | 628 | 599 | 29 |
| 1980-09-24 | vs SLN | 152 | W 6-3 | 80-72 | 3 | 4,297 | Rick Rhoden | John Martin | Rick Rhoden | John Martin | Grant Jackson | 634 | 602 | 32 |
| 1980-09-25 | vs SLN | 153 | L 2-10 | 80-73 | 3 | 6,805 | Don Robinson | Jim Kaat | Jim Kaat | Don Robinson | | 636 | 612 | 24 |
| 1980-09-26 | @ CHN | 154 | L 8-9 | 80-74 | 3 | 3,941 | John Candelaria | Dennis Lamp | Bill Caudill | Kent Tekulve | | 644 | 621 | 23 |
| 1980-09-27 | @ CHN | 155 | L 0-2 | 80-75 | 3 | 15,565 | Jim Bibby | Randy Martz | Randy Martz | Jim Bibby | Dick Tidrow | 644 | 623 | 21 |
| 1980-09-28 | @ CHN | 156 | L 2-3 | 80-76 | 3 | 10,305 | Bert Blyleven | Mike Krukow | Mike Krukow | Bert Blyleven | Bill Caudill | 646 | 626 | 20 |
| 1980-09-29 | @ NYN | 157 | L 4-5 | 80-77 | 3 | 1,787 | Rick Rhoden | Ed Lynch | Jeff Reardon | Grant Jackson | | 650 | 631 | 19 |
| 1980-09-30 | @ NYN | 158 | L 2-3 | 80-78 | 3 | 1,754 | Don Robinson | Pete Falcone | Pete Falcone | Don Robinson | | 652 | 634 | 18 |
| 1980-10-01 | @ NYN | 159 | W 10-5 | 81-78 | 3 | 2,392 | Jim Bibby | Ray Burris | Jim Bibby | Ray Burris | Enrique Romo | 662 | 639 | 23 |
| 1980-10-03 | vs CHN | 160 | W 3-1 | 82-78 | 3 | 5,270 | Jesse Jefferson | Rick Reuschel | Jesse Jefferson | Rick Reuschel | John Candelaria | 665 | 640 | 25 |
| 1980-10-04 | vs CHN | 161 | L 0-6 | 82-79 | 3 | 2,717 | Pascual Perez | Lynn McGlothen | Lynn McGlothen | Pascual Perez | | 665 | 646 | 19 |
| 1980-10-05 | vs CHN | 162 | W 1-0 | 83-79 | 3 | 20,588 | Don Robinson | Doug Capilla | Don Robinson | Doug Capilla | | 666 | 646 | 20 |