| 1980-04-10 | @ HOU | 1 | L 2-3 | 0-1 | 5 | 33,270 | Burt Hooton | J.R. Richard | J.R. Richard | Burt Hooton | Joe Sambito | 2 | 3 | -1 |
| 1980-04-11 | @ HOU | 2 | L 6-10 | 0-2 | 5 | 30,701 | Rick Sutcliffe | Joe Niekro | Dave Smith | Don Stanhouse | | 8 | 13 | -5 |
| 1980-04-12 | @ HOU | 3 | W 6-5 | 1-2 | 4 | 24,609 | Don Sutton | Nolan Ryan | Steve Howe | Dave Smith | Burt Hooton | 14 | 18 | -4 |
| 1980-04-13 | @ HOU | 4 | L 2-4 | 1-3 | 4 | 33,676 | Dave Goltz | Ken Forsch | Ken Forsch | Dave Goltz | Frank LaCorte | 16 | 22 | -6 |
| 1980-04-14 | @ SDN | 5 | L 1-2 | 1-4 | 4 | 28,650 | Bob Welch | Randy Jones | Rollie Fingers | Bobby Castillo | | 17 | 24 | -7 |
| 1980-04-15 | @ SDN | 6 | L 5-9 | 1-5 | 4 | 19,325 | Rick Sutcliffe | Rick Wise | Rick Wise | Rick Sutcliffe | Steve Mura | 22 | 33 | -11 |
| 1980-04-16 | @ SDN | 7 | W 10-4 | 2-5 | 4 | 24,861 | Burt Hooton | John Curtis | Burt Hooton | John Curtis | | 32 | 37 | -5 |
| 1980-04-17 | vs HOU | 8 | W 6-4 | 3-5 | 4 | 45,476 | Don Sutton | Nolan Ryan | Jerry Reuss | Dave Smith | | 38 | 41 | -3 |
| 1980-04-18 | vs HOU | 9 | L 4-7 | 3-6 | 4 | 41,112 | Dave Goltz | Ken Forsch | Ken Forsch | Dave Goltz | Joaquin Andujar | 42 | 48 | -6 |
| 1980-04-19 | vs HOU | 10 | L 0-2 | 3-7 | 4 | 50,112 | Bob Welch | J.R. Richard | J.R. Richard | Bob Welch | | 42 | 50 | -8 |
| 1980-04-20 | vs HOU | 11 | W 4-2 | 4-7 | 4 | 39,442 | Rick Sutcliffe | Joe Niekro | Jerry Reuss | Joe Niekro | | 46 | 52 | -6 |
| 1980-04-21 | vs SFN | 12 | W 4-3 | 5-7 | 4 | 29,779 | Burt Hooton | Vida Blue | Burt Hooton | Vida Blue | Steve Howe | 50 | 55 | -5 |
| 1980-04-22 | vs SFN | 13 | W 6-0 | 6-7 | 4 | 21,691 | Don Sutton | Bob Knepper | Don Sutton | Bob Knepper | | 56 | 55 | 1 |
| 1980-04-23 | vs SFN | 14 | W 4-0 | 7-7 | 3 | 24,822 | Dave Goltz | Ed Whitson | Dave Goltz | Ed Whitson | | 60 | 55 | 5 |
| 1980-04-24 | vs SFN | 15 | W 5-2 | 8-7 | 3 | 30,687 | Bob Welch | John Montefusco | Jerry Reuss | Gary Lavelle | | 65 | 57 | 8 |
| 1980-04-25 | vs SDN | 16 | W 6-3 | 9-7 | 3 | 39,720 | Rick Sutcliffe | Rick Wise | Bobby Castillo | Dennis Kinney | Steve Howe | 71 | 60 | 11 |
| 1980-04-26 | vs SDN | 17 | W 4-3 | 10-7 | 3 | 48,568 | Burt Hooton | Gary Lucas | Joe Beckwith | Rollie Fingers | | 75 | 63 | 12 |
| 1980-04-27 | vs SDN | 18 | W 3-1 | 11-7 | 3 | 42,756 | Don Sutton | John Curtis | Don Sutton | John Curtis | Charlie Hough | 78 | 64 | 14 |
| 1980-04-29 | @ SFN | 19 | W 5-0 | 12-7 | 3 | 16,940 | Dave Goltz | John Montefusco | Dave Goltz | John Montefusco | | 83 | 64 | 19 |
| 1980-04-30 | @ SFN | 20 | W 4-3 | 13-7 | 3 | 19,006 | Bob Welch | Vida Blue | Bob Welch | Greg Minton | Steve Howe | 87 | 67 | 20 |
| 1980-05-02 | @ PHI | 21 | L 5-9 | 13-8 | 3 | 30,294 | Rick Sutcliffe | Dick Ruthven | Ron Reed | Charlie Hough | | 92 | 76 | 16 |
| 1980-05-03 | @ PHI | 22 | L 3-7 | 13-9 | 3 | 35,011 | Burt Hooton | Larry Christenson | Larry Christenson | Burt Hooton | | 95 | 83 | 12 |
| 1980-05-04 | @ PHI | 23 | W 12-10 | 14-9 | 3 | 34,027 | Dave Goltz | Randy Lerch | Joe Beckwith | Dickie Noles | Jerry Reuss | 107 | 93 | 14 |
| 1980-05-06 | @ PIT | 24 | L 1-2 | 14-10 | 3 | 9,817 | Don Sutton | John Candelaria | Kent Tekulve | Steve Howe | | 108 | 95 | 13 |
| 1980-05-07 | @ PIT | 25 | L 6-7 | 14-11 | 3 | 11,404 | Bob Welch | Pascual Perez | Kent Tekulve | Charlie Hough | | 114 | 102 | 12 |
| 1980-05-09 | @ SLN | 26 | L 7-15 | 14-12 | 3 | 23,394 | Rick Sutcliffe | Roy Thomas | Pedro Borbon | Rick Sutcliffe | | 121 | 117 | 4 |
| 1980-05-10 | @ SLN | 27 | W 5-3 | 15-12 | 3 | 27,450 | Burt Hooton | Pete Vuckovich | Burt Hooton | Pete Vuckovich | Jerry Reuss | 126 | 120 | 6 |
| 1980-05-11 | @ SLN | 28 | W 4-2 | 16-12 | 3 | 17,696 | Dave Goltz | Bob Forsch | Dave Goltz | Bob Forsch | Jerry Reuss | 130 | 122 | 8 |
| 1980-05-12 | vs CHN | 29 | W 2-1 | 17-12 | 3 | 36,401 | Don Sutton | Rick Reuschel | Don Sutton | Rick Reuschel | Bobby Castillo | 132 | 123 | 9 |
| 1980-05-13 | vs CHN | 30 | W 4-2 | 18-12 | 3 | 32,331 | Bob Welch | Dennis Lamp | Bob Welch | Dennis Lamp | | 136 | 125 | 11 |
| 1980-05-14 | vs CHN | 31 | L 2-5 | 18-13 | 3 | 29,001 | Burt Hooton | Lynn McGlothen | Lynn McGlothen | Burt Hooton | Bruce Sutter | 138 | 130 | 8 |
| 1980-05-16 | vs PIT | 32 | W 8-6 | 19-13 | 2 | 47,929 | Jerry Reuss | John Candelaria | Jerry Reuss | Kent Tekulve | Rick Sutcliffe | 146 | 136 | 10 |
| 1980-05-17 | vs PIT | 33 | W 3-1 | 20-13 | 1 | 50,082 | Don Sutton | Bert Blyleven | Don Sutton | Bert Blyleven | Steve Howe | 149 | 137 | 12 |
| 1980-05-18 | vs PIT | 34 | W 2-0 | 21-13 | 1 | 49,867 | Bob Welch | Jim Bibby | Bob Welch | Jim Bibby | Steve Howe | 151 | 137 | 14 |
| 1980-05-19 | vs SLN | 35 | W 5-1 | 22-13 | 1 | 34,297 | Burt Hooton | Roy Thomas | Burt Hooton | Roy Thomas | | 156 | 138 | 18 |
| 1980-05-20 | vs SLN | 36 | W 4-3 | 23-13 | 1 | 29,710 | Jerry Reuss | Pete Vuckovich | Jerry Reuss | Pete Vuckovich | Rick Sutcliffe | 160 | 141 | 19 |
| 1980-05-21 | vs SLN | 37 | W 5-3 | 24-13 | 1 | 31,174 | Dave Goltz | Bob Forsch | Joe Beckwith | Mark Littell | Bobby Castillo | 165 | 144 | 21 |
| 1980-05-23 | @ CHN | 38 | L 0-2 | 24-14 | 1 | 7,482 | Don Sutton | Dennis Lamp | Dennis Lamp | Don Sutton | | 165 | 146 | 19 |
| 1980-05-24 | @ CHN | 39 | W 4-2 | 25-14 | 1 | 22,543 | Bob Welch | Mike Krukow | Bob Welch | Mike Krukow | Rick Sutcliffe | 169 | 148 | 21 |
| 1980-05-25 | @ CHN | 40 | L 1-2 | 25-15 | 1 | 27,226 | Burt Hooton | Rick Reuschel | Bruce Sutter | Steve Howe | | 170 | 150 | 20 |
| 1980-05-26 | @ CIN | 41 | W 4-0 | 26-16 | 1 | 0 | Jerry Reuss | Tom Seaver | Jerry Reuss | Tom Seaver | | 174 | 150 | 24 |
| 1980-05-26 | @ CIN | 42 | L 4-5 | 26-16 | 1 | 29,483 | Dave Goltz | Paul Moskau | Paul Moskau | Dave Goltz | Doug Bair | 178 | 155 | 23 |
| 1980-05-27 | @ CIN | 43 | L 1-6 | 26-17 | 1 | 20,296 | Don Sutton | Mike LaCoss | Mike LaCoss | Don Sutton | | 179 | 161 | 18 |
| 1980-05-29 | vs ATL | 44 | W 3-0 | 27-17 | 1 | 24,630 | Bob Welch | Phil Niekro | Bob Welch | Phil Niekro | | 182 | 161 | 21 |
| 1980-05-30 | vs ATL | 45 | W 8-4 | 28-17 | 1 | 32,200 | Burt Hooton | Rick Matula | Burt Hooton | Rick Matula | | 190 | 165 | 25 |
| 1980-05-31 | vs ATL | 46 | L 5-6 | 28-18 | 1 | 40,161 | Jerry Reuss | Tommy Boggs | Tommy Boggs | Jerry Reuss | Gene Garber | 195 | 171 | 24 |
| 1980-06-01 | vs ATL | 47 | L 5-9 | 28-19 | 1 | 49,320 | Dave Goltz | Doyle Alexander | Doyle Alexander | Dave Goltz | Rick Camp | 200 | 180 | 20 |
| 1980-06-02 | vs CIN | 48 | W 3-2 | 29-19 | 1 | 31,368 | Don Sutton | Mike LaCoss | Rick Sutcliffe | Doug Bair | | 203 | 182 | 21 |
| 1980-06-03 | vs CIN | 49 | W 5-1 | 30-19 | 1 | 44,962 | Bob Welch | Tom Seaver | Bob Welch | Tom Seaver | Steve Howe | 208 | 183 | 25 |
| 1980-06-04 | vs CIN | 50 | L 4-5 | 30-20 | 1 | 45,541 | Charlie Hough | Charlie Leibrandt | Paul Moskau | Charlie Hough | Tom Hume | 212 | 188 | 24 |
| 1980-06-06 | @ ATL | 51 | W 5-0 | 31-20 | 1 | 18,331 | Jerry Reuss | Phil Niekro | Jerry Reuss | Phil Niekro | | 217 | 188 | 29 |
| 1980-06-07 | @ ATL | 52 | L 1-6 | 31-21 | 1 | 25,723 | Dave Goltz | Doyle Alexander | Doyle Alexander | Dave Goltz | | 218 | 194 | 24 |
| 1980-06-08 | @ ATL | 53 | W 3-1 | 32-21 | 1 | 12,543 | Don Sutton | Tommy Boggs | Don Sutton | Tommy Boggs | Rick Sutcliffe | 221 | 195 | 26 |
| 1980-06-10 | @ NYN | 54 | L 4-5 | 32-22 | 2 | 14,759 | Bob Welch | Pat Zachry | Tom Hausman | Bob Welch | | 225 | 200 | 25 |
| 1980-06-11 | @ NYN | 55 | L 2-6 | 32-23 | 2 | 23,540 | Jerry Reuss | Craig Swan | Craig Swan | Rick Sutcliffe | | 227 | 206 | 21 |
| 1980-06-12 | @ NYN | 56 | L 5-6 | 32-24 | 2 | 19,501 | Dave Goltz | John Pacella | Jeff Reardon | Bobby Castillo | Neil Allen | 232 | 212 | 20 |
| 1980-06-13 | @ MON | 57 | L 3-4 | 32-25 | 3 | 34,655 | Don Sutton | Steve Rogers | Steve Rogers | Steve Howe | | 235 | 216 | 19 |
| 1980-06-14 | @ MON | 58 | W 8-0 | 33-25 | 2 | 44,585 | Burt Hooton | Ross Grimsley | Burt Hooton | Ross Grimsley | | 243 | 216 | 27 |
| 1980-06-15 | @ MON | 59 | W 1-0 | 34-25 | 2 | 36,176 | Bob Welch | Bill Gullickson | Bob Welch | Bill Gullickson | | 244 | 216 | 28 |
| 1980-06-16 | vs PHI | 60 | L 2-3 | 34-26 | 2 | 41,340 | Jerry Reuss | Randy Lerch | Ron Reed | Rick Sutcliffe | Tug McGraw | 246 | 219 | 27 |
| 1980-06-17 | vs PHI | 61 | L 5-6 | 34-27 | 2 | 40,786 | Dave Goltz | Dickie Noles | Ron Reed | Bobby Castillo | Tug McGraw | 251 | 225 | 26 |
| 1980-06-18 | vs MON | 62 | W 8-7 | 35-27 | 2 | 41,229 | Don Sutton | Steve Rogers | Charlie Hough | Elias Sosa | Steve Howe | 259 | 232 | 27 |
| 1980-06-19 | vs MON | 63 | W 5-3 | 36-27 | 2 | 35,819 | Burt Hooton | Bill Gullickson | Bobby Castillo | Woodie Fryman | | 264 | 235 | 29 |
| 1980-06-20 | vs NYN | 64 | W 4-3 | 37-27 | 2 | 48,608 | Bob Welch | Pat Zachry | Steve Howe | Pat Zachry | | 268 | 238 | 30 |
| 1980-06-21 | vs NYN | 65 | W 5-0 | 38-27 | 2 | 41,605 | Jerry Reuss | Craig Swan | Jerry Reuss | Craig Swan | | 273 | 238 | 35 |
| 1980-06-22 | vs NYN | 66 | L 6-9 | 38-28 | 2 | 43,298 | Dave Goltz | John Pacella | Mark Bomback | Dave Goltz | Neil Allen | 279 | 247 | 32 |
| 1980-06-23 | @ HOU | 67 | W 3-0 | 39-28 | 2 | 29,753 | Rick Sutcliffe | Joaquin Andujar | Rick Sutcliffe | Joaquin Andujar | | 282 | 247 | 35 |
| 1980-06-24 | @ HOU | 68 | L 4-5 | 39-29 | 2 | 34,388 | Burt Hooton | Nolan Ryan | Frank LaCorte | Joe Beckwith | | 286 | 252 | 34 |
| 1980-06-25 | @ HOU | 69 | W 9-2 | 40-29 | 2 | 34,416 | Bob Welch | Ken Forsch | Bob Welch | Ken Forsch | | 295 | 254 | 41 |
| 1980-06-27 | @ SFN | 70 | W 8-0 | 41-29 | 2 | 20,285 | Jerry Reuss | Vida Blue | Jerry Reuss | Vida Blue | | 303 | 254 | 49 |
| 1980-06-28 | @ SFN | 71 | L 3-4 | 41-30 | 2 | 25,145 | Dave Goltz | John Montefusco | Tom Griffin | Rick Sutcliffe | | 306 | 258 | 48 |
| 1980-06-29 | @ SFN | 72 | L 3-4 | 42-31 | 2 | 0 | Don Sutton | Bob Knepper | Bob Knepper | Bobby Castillo | | 309 | 262 | 47 |
| 1980-06-29 | @ SFN | 73 | W 3-0 | 42-31 | 2 | 50,229 | Burt Hooton | Allen Ripley | Burt Hooton | Allen Ripley | | 312 | 262 | 50 |
| 1980-06-30 | vs SDN | 74 | L 3-4 | 42-32 | 2 | 29,756 | Bob Welch | Juan Eichelberger | Juan Eichelberger | Bob Welch | Bob Shirley | 315 | 266 | 49 |
| 1980-07-01 | vs SDN | 75 | L 1-4 | 42-33 | 2 | 38,801 | Jerry Reuss | Steve Mura | Steve Mura | Jerry Reuss | Rollie Fingers | 316 | 270 | 46 |
| 1980-07-02 | vs SDN | 76 | W 10-7 | 43-33 | 2 | 33,232 | Dave Goltz | John Curtis | Rick Sutcliffe | Dennis Blair | | 326 | 277 | 49 |
| 1980-07-03 | vs SDN | 77 | W 5-4 | 44-33 | 2 | 31,375 | Burt Hooton | Gary Lucas | Bobby Castillo | Bob Shirley | | 331 | 281 | 50 |
| 1980-07-04 | vs SFN | 78 | W 4-0 | 45-33 | 2 | 49,846 | Don Sutton | Allen Ripley | Don Sutton | Allen Ripley | | 335 | 281 | 54 |
| 1980-07-05 | vs SFN | 79 | W 3-2 | 46-33 | 1 | 41,587 | Bob Welch | Ed Whitson | Bob Welch | Ed Whitson | Bobby Castillo | 338 | 283 | 55 |
| 1980-07-06 | vs SFN | 80 | L 4-7 | 46-34 | 2 | 46,244 | Jerry Reuss | John Montefusco | Al Holland | Steve Howe | | 342 | 290 | 52 |
| 1980-07-10 | vs HOU | 81 | W 4-3 | 47-34 | 1 | 49,692 | Burt Hooton | Nolan Ryan | Steve Howe | Nolan Ryan | | 346 | 293 | 53 |
| 1980-07-11 | vs HOU | 82 | W 3-2 | 48-34 | 1 | 42,754 | Jerry Reuss | Ken Forsch | Jerry Reuss | Ken Forsch | Steve Howe | 349 | 295 | 54 |
| 1980-07-12 | @ SDN | 83 | L 2-3 | 48-35 | 1 | 39,605 | Don Sutton | Rick Wise | Eric Rasmussen | Joe Beckwith | | 351 | 298 | 53 |
| 1980-07-13 | @ SDN | 84 | L 3-4 | 48-36 | 2 | 18,232 | Bob Welch | Juan Eichelberger | Dennis Kinney | Joe Beckwith | | 354 | 302 | 52 |
| 1980-07-14 | @ SDN | 85 | L 3-6 | 48-37 | 2 | 22,370 | Rick Sutcliffe | Steve Mura | Steve Mura | Rick Sutcliffe | | 357 | 308 | 49 |
| 1980-07-15 | @ CHN | 86 | W 6-2 | 49-37 | 2 | 20,257 | Burt Hooton | Lynn McGlothen | Burt Hooton | Lynn McGlothen | Dave Goltz | 363 | 310 | 53 |
| 1980-07-16 | @ CHN | 87 | L 1-4 | 49-38 | 2 | 18,638 | Jerry Reuss | Rick Reuschel | Rick Reuschel | Jerry Reuss | | 364 | 314 | 50 |
| 1980-07-17 | @ CHN | 88 | W 3-1 | 50-38 | 1 | 21,389 | Don Sutton | Dennis Lamp | Don Sutton | Dennis Lamp | | 367 | 315 | 52 |
| 1980-07-18 | @ PIT | 89 | L 4-6 | 50-39 | 1 | 30,131 | Bob Welch | Rick Rhoden | Rick Rhoden | Bob Welch | Enrique Romo | 371 | 321 | 50 |
| 1980-07-19 | @ PIT | 90 | L 3-7 | 50-40 | 2 | 28,731 | Rick Sutcliffe | Don Robinson | Eddie Solomon | Rick Sutcliffe | | 374 | 328 | 46 |
| 1980-07-20 | @ PIT | 91 | W 4-2 | 51-41 | 2 | 0 | Burt Hooton | John Candelaria | Burt Hooton | John Candelaria | Steve Howe | 378 | 330 | 48 |
| 1980-07-20 | @ PIT | 92 | L 7-8 | 51-41 | 2 | 41,932 | Jerry Reuss | Bert Blyleven | Grant Jackson | Bobby Castillo | | 385 | 338 | 47 |
| 1980-07-21 | @ SLN | 93 | L 2-5 | 51-42 | 2 | 20,224 | Dave Goltz | Pete Vuckovich | Pete Vuckovich | Dave Goltz | John Littlefield | 387 | 343 | 44 |
| 1980-07-22 | @ SLN | 94 | L 2-3 | 51-43 | 2 | 25,174 | Don Sutton | Jim Kaat | John Urrea | Don Sutton | John Littlefield | 389 | 346 | 43 |
| 1980-07-23 | @ SLN | 95 | L 3-7 | 51-44 | 2 | 28,654 | Bob Welch | Silvio Martinez | Silvio Martinez | Bob Welch | | 392 | 353 | 39 |
| 1980-07-25 | vs CHN | 96 | W 7-6 | 52-44 | 2 | 50,546 | Burt Hooton | Mike Krukow | Steve Howe | Bruce Sutter | | 399 | 359 | 40 |
| 1980-07-26 | vs CHN | 97 | L 3-5 | 52-45 | 2 | 50,125 | Jerry Reuss | Lynn McGlothen | Lynn McGlothen | Jerry Reuss | Bruce Sutter | 402 | 364 | 38 |
| 1980-07-27 | vs CHN | 98 | W 3-2 | 53-45 | 2 | 42,363 | Don Sutton | Rick Reuschel | Steve Howe | Bill Caudill | | 405 | 366 | 39 |
| 1980-07-28 | vs PIT | 99 | L 4-6 | 53-46 | 2 | 46,973 | Bob Welch | Rick Rhoden | Rick Rhoden | Bob Welch | Kent Tekulve | 409 | 372 | 37 |
| 1980-07-29 | vs PIT | 100 | W 10-2 | 54-46 | 2 | 47,013 | Burt Hooton | Bert Blyleven | Burt Hooton | Bert Blyleven | | 419 | 374 | 45 |
| 1980-07-30 | vs PIT | 101 | W 3-0 | 55-46 | 2 | 50,308 | Jerry Reuss | John Candelaria | Jerry Reuss | John Candelaria | | 422 | 374 | 48 |
| 1980-08-01 | vs SLN | 102 | W 2-1 | 56-46 | 2 | 43,549 | Don Sutton | Bob Forsch | Dave Goltz | Bob Forsch | | 424 | 375 | 49 |
| 1980-08-02 | vs SLN | 103 | W 3-2 | 57-46 | 1 | 49,520 | Bob Welch | Pete Vuckovich | Bob Welch | Pete Vuckovich | Don Stanhouse | 427 | 377 | 50 |
| 1980-08-03 | vs SLN | 104 | L 1-4 | 57-47 | 2 | 31,833 | Burt Hooton | Silvio Martinez | Silvio Martinez | Burt Hooton | | 428 | 381 | 47 |
| 1980-08-04 | @ ATL | 105 | W 5-3 | 58-47 | 2 | 30,330 | Jerry Reuss | Tommy Boggs | Jerry Reuss | Tommy Boggs | Don Stanhouse | 433 | 384 | 49 |
| 1980-08-05 | @ ATL | 106 | L 4-6 | 58-48 | 2 | 10,187 | Dave Goltz | Phil Niekro | Rick Camp | Don Stanhouse | | 437 | 390 | 47 |
| 1980-08-06 | @ ATL | 107 | W 6-2 | 59-48 | 2 | 9,441 | Don Sutton | Rick Matula | Don Sutton | Rick Matula | Bobby Castillo | 443 | 392 | 51 |
| 1980-08-07 | @ ATL | 108 | L 3-4 | 59-49 | 2 | 10,056 | Bob Welch | Doyle Alexander | Doyle Alexander | Bob Welch | Rick Camp | 446 | 396 | 50 |
| 1980-08-08 | @ CIN | 109 | L 5-8 | 59-50 | 2 | 40,339 | Burt Hooton | Mike LaCoss | Tom Hume | Bobby Castillo | | 451 | 404 | 47 |
| 1980-08-09 | @ CIN | 110 | W 9-4 | 60-50 | 2 | 45,095 | Jerry Reuss | Tom Seaver | Jerry Reuss | Tom Seaver | Rick Sutcliffe | 460 | 408 | 52 |
| 1980-08-10 | @ CIN | 111 | W 7-1 | 61-50 | 1 | 35,179 | Dave Goltz | Paul Moskau | Dave Goltz | Paul Moskau | | 467 | 409 | 58 |
| 1980-08-11 | vs ATL | 112 | L 2-3 | 61-51 | 1 | 32,118 | Don Sutton | Rick Matula | Rick Matula | Don Sutton | Rick Camp | 469 | 412 | 57 |
| 1980-08-12 | vs ATL | 113 | L 6-7 | 61-52 | 1 | 35,905 | Bob Welch | Doyle Alexander | Gene Garber | Rick Sutcliffe | Rick Camp | 475 | 419 | 56 |
| 1980-08-13 | vs ATL | 114 | L 0-2 | 61-53 | 2 | 36,345 | Burt Hooton | Tommy Boggs | Tommy Boggs | Burt Hooton | | 475 | 421 | 54 |
| 1980-08-15 | vs CIN | 115 | W 3-1 | 62-53 | 2 | 50,933 | Jerry Reuss | Tom Seaver | Jerry Reuss | Tom Seaver | | 478 | 422 | 56 |
| 1980-08-16 | vs CIN | 116 | L 2-3 | 62-54 | 3 | 42,743 | Don Sutton | Paul Moskau | Tom Hume | Steve Howe | | 480 | 425 | 55 |
| 1980-08-17 | vs CIN | 117 | L 2-6 | 62-55 | 3 | 47,177 | Bob Welch | Mario Soto | Mario Soto | Bob Welch | Tom Hume | 482 | 431 | 51 |
| 1980-08-19 | @ MON | 118 | W 3-2 | 63-55 | 3 | 45,320 | Burt Hooton | Charlie Lea | Don Stanhouse | Elias Sosa | | 485 | 433 | 52 |
| 1980-08-20 | @ MON | 119 | W 5-1 | 64-55 | 3 | 32,630 | Jerry Reuss | Steve Rogers | Jerry Reuss | Steve Rogers | | 490 | 434 | 56 |
| 1980-08-21 | @ MON | 120 | W 5-4 | 65-55 | 3 | 33,523 | Don Sutton | Scott Sanderson | Steve Howe | Stan Bahnsen | | 495 | 438 | 57 |
| 1980-08-22 | @ NYN | 121 | L 2-4 | 65-56 | 3 | 21,936 | Bob Welch | Ray Burris | Ray Burris | Bob Welch | Neil Allen | 497 | 442 | 55 |
| 1980-08-23 | @ NYN | 122 | W 4-2 | 66-56 | 2 | 32,440 | Dave Goltz | Roy Lee Jackson | Dave Goltz | Tom Hausman | Steve Howe | 501 | 444 | 57 |
| 1980-08-24 | @ NYN | 123 | W 3-2 | 67-56 | 2 | 24,956 | Burt Hooton | Pat Zachry | Burt Hooton | Pat Zachry | Steve Howe | 504 | 446 | 58 |
| 1980-08-25 | @ PHI | 124 | W 8-4 | 68-56 | 2 | 34,267 | Jerry Reuss | Nino Espinosa | Don Stanhouse | Dickie Noles | | 512 | 450 | 62 |
| 1980-08-26 | @ PHI | 125 | W 8-4 | 69-56 | 2 | 35,358 | Rick Sutcliffe | Bob Walk | Bobby Castillo | Bob Walk | | 520 | 454 | 66 |
| 1980-08-27 | @ PHI | 126 | L 3-4 | 69-57 | 2 | 39,116 | Bob Welch | Steve Carlton | Steve Carlton | Steve Howe | Tug McGraw | 523 | 458 | 65 |
| 1980-08-29 | vs MON | 127 | W 5-4 | 70-57 | 2 | 50,810 | Dave Goltz | Fred Norman | Bobby Castillo | John D'Acquisto | Steve Howe | 528 | 462 | 66 |
| 1980-08-30 | vs MON | 128 | W 4-3 | 71-57 | 2 | 35,778 | Burt Hooton | Bill Gullickson | Burt Hooton | Bill Gullickson | Don Stanhouse | 532 | 465 | 67 |
| 1980-08-31 | vs MON | 129 | W 2-0 | 73-57 | 2 | 0 | Jerry Reuss | Steve Rogers | Jerry Reuss | Steve Rogers | | 534 | 465 | 69 |
| 1980-08-31 | vs MON | 130 | W 7-2 | 73-57 | 2 | 48,542 | Don Sutton | David Palmer | Don Sutton | David Palmer | | 541 | 467 | 74 |
| 1980-09-01 | vs NYN | 131 | W 5-2 | 74-57 | 2 | 30,460 | Bob Welch | Ray Burris | Bob Welch | Ray Burris | Steve Howe | 546 | 469 | 77 |
| 1980-09-02 | vs NYN | 132 | W 6-5 | 75-57 | 2 | 27,543 | Dave Goltz | John Pacella | Dave Goltz | John Pacella | Don Stanhouse | 552 | 474 | 78 |
| 1980-09-03 | vs NYN | 133 | W 2-0 | 76-57 | 1 | 28,568 | Burt Hooton | Pat Zachry | Burt Hooton | Pat Zachry | Steve Howe | 554 | 474 | 80 |
| 1980-09-04 | vs PHI | 134 | L 2-3 | 76-58 | 1 | 41,864 | Jerry Reuss | Bob Walk | Bob Walk | Jerry Reuss | Tug McGraw | 556 | 477 | 79 |
| 1980-09-05 | vs PHI | 135 | W 1-0 | 77-58 | 1 | 41,019 | Don Sutton | Steve Carlton | Don Sutton | Steve Carlton | Don Stanhouse | 557 | 477 | 80 |
| 1980-09-06 | vs PHI | 136 | W 7-3 | 78-58 | 1 | 45,995 | Bob Welch | Larry Christenson | Bob Welch | Randy Lerch | Steve Howe | 564 | 480 | 84 |
| 1980-09-07 | vs PHI | 137 | W 6-0 | 79-58 | 1 | 39,083 | Dave Goltz | Dick Ruthven | Bobby Castillo | Dick Ruthven | | 570 | 480 | 90 |
| 1980-09-09 | @ HOU | 138 | L 4-5 | 79-59 | 1 | 34,546 | Jerry Reuss | Joaquin Andujar | Dave Smith | Steve Howe | Joe Sambito | 574 | 485 | 89 |
| 1980-09-10 | @ HOU | 139 | L 5-6 | 79-60 | 2 | 37,632 | Burt Hooton | Nolan Ryan | Bert Roberge | Rick Sutcliffe | | 579 | 491 | 88 |
| 1980-09-12 | @ CIN | 140 | W 5-2 | 80-60 | 2 | 36,287 | Don Sutton | Mike LaCoss | Don Sutton | Mike LaCoss | Steve Howe | 584 | 493 | 91 |
| 1980-09-13 | @ CIN | 141 | W 3-2 | 81-60 | 2 | 38,542 | Bob Welch | Frank Pastore | Bobby Castillo | Mario Soto | Don Stanhouse | 587 | 495 | 92 |
| 1980-09-14 | @ CIN | 142 | W 3-1 | 82-60 | 2 | 34,038 | Jerry Reuss | Paul Moskau | Jerry Reuss | Paul Moskau | | 590 | 496 | 94 |
| 1980-09-15 | @ ATL | 143 | L 0-9 | 82-61 | 2 | 8,025 | Burt Hooton | Tommy Boggs | Tommy Boggs | Burt Hooton | | 590 | 505 | 85 |
| 1980-09-16 | @ ATL | 144 | L 1-2 | 82-62 | 2 | 31,279 | Dave Goltz | Phil Niekro | Phil Niekro | Dave Goltz | Rick Camp | 591 | 507 | 84 |
| 1980-09-17 | vs SDN | 145 | W 2-1 | 83-62 | 1 | 28,822 | Don Sutton | Juan Eichelberger | Don Sutton | Juan Eichelberger | Steve Howe | 593 | 508 | 85 |
| 1980-09-18 | vs SDN | 146 | W 7-3 | 84-62 | 1 | 30,738 | Bob Welch | Rick Wise | Bob Welch | Rick Wise | Bobby Castillo | 600 | 511 | 89 |
| 1980-09-19 | vs CIN | 147 | L 7-10 | 84-63 | 1 | 46,609 | Jerry Reuss | Paul Moskau | Mike LaCoss | Jerry Reuss | Tom Hume | 607 | 521 | 86 |
| 1980-09-20 | vs CIN | 148 | L 2-10 | 84-64 | 2 | 50,240 | Burt Hooton | Tom Seaver | Tom Seaver | Burt Hooton | | 609 | 531 | 78 |
| 1980-09-21 | vs CIN | 149 | L 2-7 | 84-65 | 2 | 43,716 | Dave Goltz | Mario Soto | Tom Hume | Steve Howe | | 611 | 538 | 73 |
| 1980-09-22 | vs ATL | 150 | L 2-7 | 84-66 | 2 | 25,078 | Don Sutton | Preston Hanna | Preston Hanna | Don Sutton | Rick Camp | 613 | 545 | 68 |
| 1980-09-23 | vs ATL | 151 | W 4-2 | 85-66 | 2 | 29,226 | Bob Welch | Rick Matula | Bob Welch | Rick Matula | Don Stanhouse | 617 | 547 | 70 |
| 1980-09-24 | vs SFN | 152 | W 5-4 | 86-66 | 2 | 35,581 | Jerry Reuss | Tom Griffin | Bobby Castillo | Mike Rowland | | 622 | 551 | 71 |
| 1980-09-25 | vs SFN | 153 | L 2-3 | 86-67 | 2 | 33,460 | Burt Hooton | Ed Whitson | Ed Whitson | Burt Hooton | Gary Lavelle | 624 | 554 | 70 |
| 1980-09-26 | @ SDN | 154 | L 2-3 | 86-68 | 2 | 14,836 | Dave Goltz | Steve Mura | Tom Tellmann | Dave Goltz | Rollie Fingers | 626 | 557 | 69 |
| 1980-09-27 | @ SDN | 155 | W 6-4 | 87-68 | 2 | 19,260 | Don Sutton | Eric Rasmussen | Don Sutton | Eric Rasmussen | Fernando Valenzuela | 632 | 561 | 71 |
| 1980-09-28 | @ SDN | 156 | L 5-7 | 87-69 | 2 | 17,971 | Bob Welch | Juan Eichelberger | Rollie Fingers | Steve Howe | Tom Tellmann | 637 | 568 | 69 |
| 1980-09-30 | @ SFN | 157 | W 6-3 | 88-69 | 2 | 10,953 | Jerry Reuss | Tom Griffin | Fernando Valenzuela | Gary Lavelle | | 643 | 571 | 72 |
| 1980-10-01 | @ SFN | 158 | W 8-4 | 89-69 | 2 | 11,307 | Burt Hooton | Ed Whitson | Burt Hooton | Ed Whitson | | 651 | 575 | 76 |
| 1980-10-02 | @ SFN | 159 | L 2-3 | 89-70 | 2 | 11,693 | Dave Goltz | Vida Blue | Greg Minton | Dave Goltz | Al Holland | 653 | 578 | 75 |
| 1980-10-03 | vs HOU | 160 | W 3-2 | 90-70 | 2 | 49,642 | Don Sutton | Ken Forsch | Fernando Valenzuela | Ken Forsch | | 656 | 580 | 76 |
| 1980-10-04 | vs HOU | 161 | W 2-1 | 91-70 | 2 | 46,085 | Jerry Reuss | Nolan Ryan | Jerry Reuss | Nolan Ryan | | 658 | 581 | 77 |
| 1980-10-05 | vs HOU | 162 | W 4-3 | 92-70 | 2 | 52,339 | Burt Hooton | Vern Ruhle | Steve Howe | Frank LaCorte | Don Sutton | 662 | 584 | 78 |
| 1980-10-06 | vs HOU | 163 | L 1-7 | 92-71 | 2 | 51,127 | Dave Goltz | Joe Niekro | Joe Niekro | Dave Goltz | | 663 | 591 | 72 |