| 1978-04-07 | vs MON | 1 | W 3-1 | 1-0 | 1 | 11,736 | Jerry Koosman | Steve Rogers | Jerry Koosman | Steve Rogers | | 3 | 1 | 2 |
| 1978-04-08 | vs MON | 2 | W 6-5 | 2-0 | 1 | 7,259 | Nino Espinosa | Rudy May | Mardie Cornejo | Stan Bahnsen | | 9 | 6 | 3 |
| 1978-04-09 | vs MON | 3 | W 6-5 | 3-1 | 1 | 0 | Pat Zachry | Wayne Twitchell | Pat Zachry | Wayne Twitchell | Mardie Cornejo | 15 | 11 | 4 |
| 1978-04-09 | vs MON | 4 | L 0-5 | 3-1 | 1 | 30,448 | Mike Bruhert | Ross Grimsley | Ross Grimsley | Mike Bruhert | | 15 | 16 | -1 |
| 1978-04-10 | vs CHN | 5 | W 6-0 | 4-1 | 1 | 3,751 | Craig Swan | Dennis Lamp | Craig Swan | Dennis Lamp | | 21 | 16 | 5 |
| 1978-04-11 | vs CHN | 6 | L 2-4 | 4-2 | 1 | 3,653 | Jerry Koosman | Rick Reuschel | Rick Reuschel | Jerry Koosman | Donnie Moore | 23 | 20 | 3 |
| 1978-04-12 | vs CHN | 7 | L 2-4 | 4-3 | 2 | 6,024 | Nino Espinosa | Ray Burris | Ray Burris | Nino Espinosa | | 25 | 24 | 1 |
| 1978-04-14 | @ MON | 8 | W 3-2 | 5-3 | 1 | 37,172 | Pat Zachry | Rudy May | Mardie Cornejo | Rudy May | Skip Lockwood | 28 | 26 | 2 |
| 1978-04-15 | @ MON | 9 | L 3-4 | 5-4 | 2 | 12,617 | Craig Swan | Wayne Twitchell | Bill Atkinson | Bob Myrick | | 31 | 30 | 1 |
| 1978-04-16 | @ MON | 10 | L 1-4 | 5-5 | 5 | 18,790 | Jerry Koosman | Ross Grimsley | Ross Grimsley | Jerry Koosman | | 32 | 34 | -2 |
| 1978-04-17 | @ SLN | 11 | W 6-2 | 6-5 | 3 | 6,371 | Nino Espinosa | Pete Falcone | Nino Espinosa | Pete Falcone | Skip Lockwood | 38 | 36 | 2 |
| 1978-04-18 | @ SLN | 12 | W 3-2 | 7-5 | 3 | 5,728 | Mike Bruhert | Eric Rasmussen | Mike Bruhert | Eric Rasmussen | Skip Lockwood | 41 | 38 | 3 |
| 1978-04-19 | @ SLN | 13 | W 2-0 | 8-5 | 2 | 6,958 | Pat Zachry | Mark Littell | Pat Zachry | Mark Littell | | 43 | 38 | 5 |
| 1978-04-21 | @ CHN | 14 | L 0-5 | 8-6 | 3 | 4,124 | Craig Swan | Dennis Lamp | Dennis Lamp | Craig Swan | | 43 | 43 | 0 |
| 1978-04-22 | @ CHN | 15 | W 3-2 | 9-6 | 1 | 13,785 | Jerry Koosman | Rick Reuschel | Mardie Cornejo | Rick Reuschel | Skip Lockwood | 46 | 45 | 1 |
| 1978-04-23 | @ CHN | 16 | L 2-3 | 9-7 | 3 | 7,692 | Nino Espinosa | Ray Burris | Guillermo Hernandez | Butch Metzger | | 48 | 48 | 0 |
| 1978-04-24 | vs PIT | 17 | L 2-4 | 9-8 | 3 | 9,495 | Pat Zachry | Jim Rooker | Kent Tekulve | Mardie Cornejo | | 50 | 52 | -2 |
| 1978-04-25 | vs PIT | 18 | L 1-2 | 9-9 | 5 | 6,914 | Mike Bruhert | Don Robinson | Don Robinson | Mike Bruhert | | 51 | 54 | -3 |
| 1978-04-26 | vs PIT | 19 | L 0-1 | 9-10 | 5 | 6,506 | Craig Swan | Bert Blyleven | Bert Blyleven | Bob Myrick | | 51 | 55 | -4 |
| 1978-04-28 | vs CIN | 20 | L 1-5 | 9-11 | 5 | 15,842 | Jerry Koosman | Fred Norman | Fred Norman | Jerry Koosman | Manny Sarmiento | 52 | 60 | -8 |
| 1978-04-29 | vs CIN | 21 | L 7-14 | 9-12 | 5 | 17,347 | Nino Espinosa | Doug Capilla | Pedro Borbon | Mardie Cornejo | Doug Bair | 59 | 74 | -15 |
| 1978-04-30 | vs CIN | 22 | W 6-4 | 10-12 | 5 | 20,092 | Pat Zachry | Tom Hume | Pat Zachry | Tom Hume | Skip Lockwood | 65 | 78 | -13 |
| 1978-05-01 | @ ATL | 23 | L 5-6 | 10-13 | 5 | 5,399 | Craig Swan | Preston Hanna | Eddie Solomon | Skip Lockwood | | 70 | 84 | -14 |
| 1978-05-02 | @ ATL | 24 | L 4-5 | 10-14 | 6 | 4,682 | Mike Bruhert | Dick Ruthven | Adrian Devine | Bob Myrick | | 74 | 89 | -15 |
| 1978-05-04 | @ ATL | 25 | W 8-2 | 11-14 | 5 | 6,195 | Jerry Koosman | Phil Niekro | Jerry Koosman | Phil Niekro | | 82 | 91 | -9 |
| 1978-05-05 | @ PHI | 26 | L 4-9 | 11-15 | 5 | 22,116 | Nino Espinosa | Jim Lonborg | Jim Lonborg | Nino Espinosa | Tug McGraw | 86 | 100 | -14 |
| 1978-05-06 | @ PHI | 27 | L 2-7 | 11-16 | 6 | 22,250 | Pat Zachry | Steve Carlton | Steve Carlton | Pat Zachry | | 88 | 107 | -19 |
| 1978-05-07 | @ PHI | 28 | L 5-8 | 11-17 | 6 | 39,106 | Craig Swan | Randy Lerch | Gene Garber | Craig Swan | Tug McGraw | 93 | 115 | -22 |
| 1978-05-08 | @ CIN | 29 | W 3-2 | 12-17 | 6 | 16,094 | Mike Bruhert | Fred Norman | Skip Lockwood | Pedro Borbon | Mardie Cornejo | 96 | 117 | -21 |
| 1978-05-09 | @ CIN | 30 | L 6-7 | 12-18 | 6 | 19,217 | Jerry Koosman | Tom Hume | Doug Bair | Skip Lockwood | | 102 | 124 | -22 |
| 1978-05-10 | @ MON | 31 | W 7-2 | 13-18 | 6 | 7,279 | Nino Espinosa | Rudy May | Nino Espinosa | Rudy May | | 109 | 126 | -17 |
| 1978-05-11 | @ MON | 32 | W 3-2 | 14-18 | 6 | 6,930 | Pat Zachry | Wayne Twitchell | Pat Zachry | Stan Bahnsen | Skip Lockwood | 112 | 128 | -16 |
| 1978-05-12 | vs HOU | 33 | L 4-5 | 14-19 | 6 | 8,649 | Craig Swan | Joaquin Andujar | Tom Dixon | Skip Lockwood | | 116 | 133 | -17 |
| 1978-05-13 | vs HOU | 34 | L 4-7 | 14-20 | 6 | 19,838 | Mike Bruhert | Joe Niekro | Joe Niekro | Mike Bruhert | Joe Sambito | 120 | 140 | -20 |
| 1978-05-17 | vs ATL | 35 | L 1-2 | 15-21 | 5 | 0 | Jerry Koosman | Phil Niekro | Phil Niekro | Jerry Koosman | | 121 | 142 | -21 |
| 1978-05-17 | vs ATL | 36 | W 3-1 | 15-21 | 5 | 4,054 | Nino Espinosa | Tommy Boggs | Nino Espinosa | Tommy Boggs | | 124 | 143 | -19 |
| 1978-05-18 | vs ATL | 37 | W 8-7 | 16-21 | 5 | 4,431 | Pat Zachry | Preston Hanna | Skip Lockwood | Eddie Solomon | | 132 | 150 | -18 |
| 1978-05-19 | vs PHI | 38 | W 4-3 | 17-21 | 5 | 13,181 | Craig Swan | Jim Kaat | Skip Lockwood | Tug McGraw | | 136 | 153 | -17 |
| 1978-05-20 | vs PHI | 39 | L 4-9 | 17-22 | 5 | 14,110 | Mike Bruhert | Steve Carlton | Tug McGraw | Dale Murray | | 140 | 162 | -22 |
| 1978-05-21 | vs PHI | 40 | W 6-5 | 18-22 | 5 | 18,183 | Jerry Koosman | Randy Lerch | Skip Lockwood | Tug McGraw | | 146 | 167 | -21 |
| 1978-05-23 | @ PIT | 41 | W 7-3 | 19-22 | 4 | 2,869 | Nino Espinosa | Jerry Reuss | Nino Espinosa | Grant Jackson | Skip Lockwood | 153 | 170 | -17 |
| 1978-05-24 | @ PIT | 42 | L 5-6 | 19-23 | 5 | 5,302 | Pat Zachry | Don Robinson | Kent Tekulve | Skip Lockwood | | 158 | 176 | -18 |
| 1978-05-25 | @ PIT | 43 | W 3-2 | 20-23 | 4 | 5,766 | Craig Swan | Bert Blyleven | Dale Murray | Kent Tekulve | | 161 | 178 | -17 |
| 1978-05-26 | @ HOU | 44 | L 4-5 | 20-24 | 5 | 11,158 | Jerry Koosman | Mark Lemongello | Mark Lemongello | Jerry Koosman | Ken Forsch | 165 | 183 | -18 |
| 1978-05-27 | @ HOU | 45 | W 9-7 | 21-24 | 4 | 26,742 | Mike Bruhert | Joaquin Andujar | Butch Metzger | Joe Sambito | Dale Murray | 174 | 190 | -16 |
| 1978-05-28 | @ HOU | 46 | W 4-1 | 22-24 | 4 | 12,133 | Nino Espinosa | Tom Dixon | Nino Espinosa | Tom Dixon | | 178 | 191 | -13 |
| 1978-05-29 | vs SLN | 47 | W 7-2 | 23-25 | 4 | 0 | Pat Zachry | John Urrea | Pat Zachry | John Urrea | | 185 | 193 | -8 |
| 1978-05-29 | vs SLN | 48 | L 2-6 | 23-25 | 4 | 28,896 | Craig Swan | Pete Falcone | Pete Vuckovich | Craig Swan | | 187 | 199 | -12 |
| 1978-05-30 | vs SLN | 49 | L 2-8 | 23-26 | 4 | 13,412 | Jerry Koosman | Silvio Martinez | Silvio Martinez | Jerry Koosman | | 189 | 207 | -18 |
| 1978-05-31 | vs SLN | 50 | L 4-5 | 23-27 | 5 | 3,933 | Mike Bruhert | Bob Forsch | Bob Forsch | Mike Bruhert | Buddy Schultz | 193 | 212 | -19 |
| 1978-06-02 | vs SDN | 51 | L 4-5 | 23-28 | 5 | 9,943 | Nino Espinosa | Randy Jones | Randy Jones | Nino Espinosa | Rollie Fingers | 197 | 217 | -20 |
| 1978-06-03 | vs SDN | 52 | W 3-2 | 24-28 | 4 | 7,452 | Pat Zachry | Bob Owchinko | Pat Zachry | Bob Owchinko | Skip Lockwood | 200 | 219 | -19 |
| 1978-06-04 | vs SDN | 53 | L 2-5 | 24-29 | 5 | 12,887 | Jerry Koosman | Gaylord Perry | Gaylord Perry | Jerry Koosman | Rollie Fingers | 202 | 224 | -22 |
| 1978-06-05 | vs LAN | 54 | W 9-8 | 25-29 | 4 | 14,435 | Mike Bruhert | Rick Rhoden | Skip Lockwood | Terry Forster | | 211 | 232 | -21 |
| 1978-06-06 | vs LAN | 55 | L 2-8 | 25-30 | 5 | 17,377 | Nino Espinosa | Doug Rau | Doug Rau | Nino Espinosa | | 213 | 240 | -27 |
| 1978-06-07 | vs LAN | 56 | W 3-2 | 26-30 | 4 | 7,453 | Pat Zachry | Burt Hooton | Pat Zachry | Charlie Hough | | 216 | 242 | -26 |
| 1978-06-09 | vs SFN | 57 | W 3-2 | 27-30 | 4 | 17,487 | Jerry Koosman | Bob Knepper | Skip Lockwood | Bob Knepper | | 219 | 244 | -25 |
| 1978-06-10 | vs SFN | 58 | L 1-2 | 27-31 | 4 | 51,220 | Kevin Kobel | Vida Blue | Vida Blue | Kevin Kobel | Gary Lavelle | 220 | 246 | -26 |
| 1978-06-11 | vs SFN | 59 | L 5-7 | 27-32 | 5 | 20,987 | Nino Espinosa | John Montefusco | John Montefusco | Nino Espinosa | Gary Lavelle | 225 | 253 | -28 |
| 1978-06-12 | @ SDN | 60 | L 2-3 | 27-33 | 5 | 19,431 | Pat Zachry | Randy Jones | Mark Lee | Pat Zachry | | 227 | 256 | -29 |
| 1978-06-13 | @ SDN | 61 | W 3-2 | 28-33 | 4 | 12,927 | Craig Swan | Bob Owchinko | Skip Lockwood | Rollie Fingers | Paul Siebert | 230 | 258 | -28 |
| 1978-06-14 | @ LAN | 62 | L 3-5 | 28-34 | 5 | 31,185 | Jerry Koosman | Tommy John | Tommy John | Jerry Koosman | Charlie Hough | 233 | 263 | -30 |
| 1978-06-15 | @ LAN | 63 | L 0-3 | 28-35 | 5 | 31,308 | Nino Espinosa | Rick Rhoden | Rick Rhoden | Nino Espinosa | Charlie Hough | 233 | 266 | -33 |
| 1978-06-16 | @ SFN | 64 | L 4-7 | 28-36 | 5 | 16,429 | Kevin Kobel | Ed Halicki | Gary Lavelle | Skip Lockwood | | 237 | 273 | -36 |
| 1978-06-17 | @ SFN | 65 | W 5-4 | 29-36 | 5 | 19,648 | Pat Zachry | Bob Knepper | Pat Zachry | Bob Knepper | Dale Murray | 242 | 277 | -35 |
| 1978-06-18 | @ SFN | 66 | L 0-3 | 29-38 | 5 | 0 | Craig Swan | Vida Blue | Vida Blue | Craig Swan | | 242 | 280 | -38 |
| 1978-06-18 | @ SFN | 67 | L 3-4 | 29-38 | 5 | 35,496 | Jerry Koosman | Jim Barr | Randy Moffitt | Dale Murray | | 245 | 284 | -39 |
| 1978-06-20 | vs MON | 68 | W 3-0 | 30-38 | 5 | 11,950 | Nino Espinosa | Ross Grimsley | Nino Espinosa | Ross Grimsley | | 248 | 284 | -36 |
| 1978-06-21 | vs MON | 69 | L 1-2 | 30-39 | 5 | 6,691 | Mike Bruhert | Steve Rogers | Steve Rogers | Mike Bruhert | | 249 | 286 | -37 |
| 1978-06-22 | vs MON | 70 | L 0-2 | 30-40 | 5 | 7,800 | Pat Zachry | Hal Dues | Hal Dues | Pat Zachry | Mike Garman | 249 | 288 | -39 |
| 1978-06-23 | vs PIT | 71 | W 3-2 | 31-40 | 5 | 16,594 | Jerry Koosman | Don Robinson | Dale Murray | Ed Whitson | | 252 | 290 | -38 |
| 1978-06-24 | vs PIT | 72 | L 4-7 | 31-41 | 5 | 17,810 | Craig Swan | Jim Bibby | Kent Tekulve | Paul Siebert | Dave Hamilton | 256 | 297 | -41 |
| 1978-06-25 | vs PIT | 73 | L 0-4 | 31-42 | 5 | 16,748 | Nino Espinosa | Bert Blyleven | Bert Blyleven | Nino Espinosa | | 256 | 301 | -45 |
| 1978-06-26 | @ CHN | 74 | L 9-10 | 31-43 | 5 | 12,188 | Mike Bruhert | Ray Burris | Lynn McGlothen | Butch Metzger | Bruce Sutter | 265 | 311 | -46 |
| 1978-06-27 | @ CHN | 75 | W 7-2 | 32-43 | 5 | 16,987 | Pat Zachry | Dennis Lamp | Pat Zachry | Dennis Lamp | | 272 | 313 | -41 |
| 1978-06-28 | @ CHN | 76 | L 8-9 | 32-44 | 5 | 24,278 | Jerry Koosman | Ken Holtzman | Ray Burris | Butch Metzger | | 280 | 322 | -42 |
| 1978-06-29 | @ PIT | 77 | L 3-4 | 32-45 | 5 | 6,367 | Craig Swan | Bert Blyleven | Grant Jackson | Skip Lockwood | Ed Whitson | 283 | 326 | -43 |
| 1978-06-30 | @ PIT | 78 | W 6-5 | 33-45 | 5 | 31,947 | Nino Espinosa | Don Robinson | Dale Murray | Dave Hamilton | | 289 | 331 | -42 |
| 1978-07-01 | @ PIT | 79 | L 0-1 | 33-46 | 5 | 7,912 | Kevin Kobel | Jim Rooker | Jim Rooker | Skip Lockwood | Kent Tekulve | 289 | 332 | -43 |
| 1978-07-04 | vs PHI | 80 | W 4-0 | 34-47 | 5 | 0 | Pat Zachry | Larry Christenson | Pat Zachry | Larry Christenson | | 293 | 332 | -39 |
| 1978-07-04 | vs PHI | 81 | L 2-3 | 34-47 | 5 | 10,410 | Craig Swan | Jim Lonborg | Rawly Eastwick | Craig Swan | Ron Reed | 295 | 335 | -40 |
| 1978-07-05 | vs PHI | 82 | L 5-7 | 34-48 | 5 | 8,667 | Jerry Koosman | Steve Carlton | Warren Brusstar | Jerry Koosman | Tug McGraw | 300 | 342 | -42 |
| 1978-07-06 | vs CHN | 83 | W 9-6 | 35-48 | 5 | 10,061 | Nino Espinosa | Dennis Lamp | Nino Espinosa | Lynn McGlothen | Skip Lockwood | 309 | 348 | -39 |
| 1978-07-07 | vs CHN | 84 | L 7-9 | 35-49 | 5 | 13,815 | Tom Hausman | Dave Roberts | Lynn McGlothen | Paul Siebert | Bruce Sutter | 316 | 357 | -41 |
| 1978-07-08 | vs CHN | 85 | W 7-0 | 36-49 | 5 | 23,007 | Kevin Kobel | Ray Burris | Kevin Kobel | Ray Burris | | 323 | 357 | -34 |
| 1978-07-09 | vs CHN | 86 | L 1-4 | 36-50 | 5 | 14,637 | Pat Zachry | Mike Krukow | Mike Krukow | Pat Zachry | Bruce Sutter | 324 | 361 | -37 |
| 1978-07-13 | @ CIN | 87 | W 4-2 | 37-50 | 5 | 35,226 | Jerry Koosman | Tom Seaver | Jerry Koosman | Tom Seaver | Skip Lockwood | 328 | 363 | -35 |
| 1978-07-14 | @ CIN | 88 | L 3-6 | 37-51 | 5 | 34,751 | Pat Zachry | Fred Norman | Doug Bair | Pat Zachry | | 331 | 369 | -38 |
| 1978-07-15 | @ CIN | 89 | L 5-7 | 37-52 | 5 | 50,125 | Craig Swan | Paul Moskau | Dave Tomlin | Dale Murray | Manny Sarmiento | 336 | 376 | -40 |
| 1978-07-16 | @ CIN | 90 | L 2-9 | 37-53 | 5 | 33,519 | Kevin Kobel | Tom Hume | Tom Hume | Kevin Kobel | | 338 | 385 | -47 |
| 1978-07-17 | @ ATL | 91 | L 0-3 | 38-54 | 5 | 0 | Nino Espinosa | Larry McWilliams | Larry McWilliams | Nino Espinosa | Gene Garber | 338 | 388 | -50 |
| 1978-07-17 | @ ATL | 92 | W 7-4 | 38-54 | 5 | 11,822 | Tom Hausman | Mickey Mahler | Tom Hausman | Mickey Mahler | Skip Lockwood | 345 | 392 | -47 |
| 1978-07-18 | @ ATL | 93 | L 3-4 | 38-55 | 5 | 10,902 | Jerry Koosman | Phil Niekro | Phil Niekro | Jerry Koosman | | 348 | 396 | -48 |
| 1978-07-19 | vs HOU | 94 | L 3-8 | 39-56 | 5 | 0 | Pat Zachry | Tom Dixon | Tom Dixon | Pat Zachry | Joe Sambito | 351 | 404 | -53 |
| 1978-07-19 | vs HOU | 95 | W 2-1 | 39-56 | 5 | 13,539 | Craig Swan | Mark Lemongello | Craig Swan | Mark Lemongello | | 353 | 405 | -52 |
| 1978-07-20 | vs HOU | 96 | W 7-4 | 41-56 | 5 | 0 | Mike Bruhert | Floyd Bannister | Mike Bruhert | Floyd Bannister | Skip Lockwood | 360 | 409 | -49 |
| 1978-07-20 | vs HOU | 97 | W 5-4 | 41-56 | 5 | 13,341 | Dwight Bernard | Vern Ruhle | Dale Murray | Joe Sambito | | 365 | 413 | -48 |
| 1978-07-21 | vs ATL | 98 | W 12-3 | 42-56 | 5 | 10,636 | Nino Espinosa | Preston Hanna | Nino Espinosa | Preston Hanna | | 377 | 416 | -39 |
| 1978-07-22 | vs ATL | 99 | W 2-0 | 43-56 | 5 | 12,277 | Tom Hausman | Phil Niekro | Tom Hausman | Phil Niekro | Skip Lockwood | 379 | 416 | -37 |
| 1978-07-23 | vs ATL | 100 | L 0-3 | 43-57 | 5 | 10,684 | Jerry Koosman | Larry McWilliams | Larry McWilliams | Jerry Koosman | Gene Garber | 379 | 419 | -40 |
| 1978-07-24 | vs CIN | 101 | L 3-5 | 43-58 | 5 | 35,939 | Pat Zachry | Paul Moskau | Manny Sarmiento | Skip Lockwood | | 382 | 424 | -42 |
| 1978-07-25 | vs CIN | 102 | W 9-2 | 44-58 | 5 | 38,158 | Craig Swan | Tom Hume | Craig Swan | Tom Hume | | 391 | 426 | -35 |
| 1978-07-26 | vs CIN | 103 | W 12-3 | 45-58 | 5 | 19,892 | Nino Espinosa | Mike LaCoss | Nino Espinosa | Mike LaCoss | | 403 | 429 | -26 |
| 1978-07-27 | @ HOU | 104 | L 3-8 | 45-59 | 5 | 9,730 | Tom Hausman | J.R. Richard | J.R. Richard | Tom Hausman | | 406 | 437 | -31 |
| 1978-07-28 | @ HOU | 105 | L 3-4 | 45-60 | 5 | 26,779 | Jerry Koosman | Tom Dixon | Joe Sambito | Skip Lockwood | | 409 | 441 | -32 |
| 1978-07-30 | @ HOU | 106 | L 3-4 | 45-61 | 5 | 17,502 | Craig Swan | Mark Lemongello | Joaquin Andujar | Dwight Bernard | | 412 | 445 | -33 |
| 1978-07-31 | @ PHI | 107 | L 1-6 | 45-62 | 5 | 21,133 | Nino Espinosa | Dick Ruthven | Dick Ruthven | Nino Espinosa | | 413 | 451 | -38 |
| 1978-08-01 | @ PHI | 108 | W 5-1 | 46-62 | 5 | 31,085 | Tom Hausman | Steve Carlton | Kevin Kobel | Steve Carlton | | 418 | 452 | -34 |
| 1978-08-02 | @ PHI | 109 | L 6-8 | 46-63 | 5 | 32,382 | Jerry Koosman | Randy Lerch | Randy Lerch | Jerry Koosman | Tug McGraw | 424 | 460 | -36 |
| 1978-08-04 | @ SLN | 110 | W 8-3 | 47-63 | 5 | 15,153 | Craig Swan | Bob Forsch | Craig Swan | Bob Forsch | | 432 | 463 | -31 |
| 1978-08-05 | @ SLN | 111 | L 3-5 | 47-64 | 5 | 19,689 | Nino Espinosa | Pete Falcone | Tom Bruno | Nino Espinosa | Mark Littell | 435 | 468 | -33 |
| 1978-08-06 | @ SLN | 112 | L 1-3 | 47-65 | 5 | 17,198 | Jerry Koosman | Silvio Martinez | Silvio Martinez | Jerry Koosman | Roy Thomas | 436 | 471 | -35 |
| 1978-08-08 | @ MON | 113 | L 1-6 | 47-66 | 5 | 17,124 | Tom Hausman | Dan Schatzeder | Dan Schatzeder | Tom Hausman | | 437 | 477 | -40 |
| 1978-08-09 | @ MON | 114 | W 10-3 | 48-66 | 5 | 16,910 | Craig Swan | Woodie Fryman | Craig Swan | Wayne Twitchell | | 447 | 480 | -33 |
| 1978-08-11 | vs SLN | 115 | L 1-4 | 48-67 | 5 | 10,434 | Jerry Koosman | Silvio Martinez | Aurelio Lopez | Dale Murray | Tom Bruno | 448 | 484 | -36 |
| 1978-08-12 | vs SLN | 116 | L 1-5 | 48-68 | 5 | 8,623 | Kevin Kobel | John Denny | John Denny | Kevin Kobel | | 449 | 489 | -40 |
| 1978-08-13 | vs SLN | 117 | L 1-6 | 48-69 | 5 | 11,088 | Mike Bruhert | Pete Vuckovich | Pete Vuckovich | Mike Bruhert | | 450 | 495 | -45 |
| 1978-08-15 | vs SDN | 118 | W 3-1 | 49-69 | 5 | 9,956 | Craig Swan | Randy Jones | Craig Swan | Randy Jones | Skip Lockwood | 453 | 496 | -43 |
| 1978-08-16 | vs SDN | 119 | L 1-2 | 49-70 | 5 | 10,263 | Jerry Koosman | Bob Owchinko | John D'Acquisto | Skip Lockwood | | 454 | 498 | -44 |
| 1978-08-17 | vs SDN | 120 | L 2-9 | 49-71 | 6 | 9,003 | Juan Berenguer | Gaylord Perry | Gaylord Perry | Juan Berenguer | Mickey Lolich | 456 | 507 | -51 |
| 1978-08-18 | vs LAN | 121 | L 3-7 | 49-72 | 6 | 26,660 | Nino Espinosa | Tommy John | Tommy John | Nino Espinosa | Charlie Hough | 459 | 514 | -55 |
| 1978-08-19 | vs LAN | 122 | W 8-4 | 50-72 | 6 | 22,963 | Mike Bruhert | Don Sutton | Dale Murray | Don Sutton | Skip Lockwood | 467 | 518 | -51 |
| 1978-08-20 | vs LAN | 123 | L 4-5 | 50-73 | 6 | 34,745 | Craig Swan | Doug Rau | Charlie Hough | Skip Lockwood | Terry Forster | 471 | 523 | -52 |
| 1978-08-21 | vs SFN | 124 | L 2-4 | 50-74 | 6 | 16,605 | Jerry Koosman | Vida Blue | Randy Moffitt | Kevin Kobel | Gary Lavelle | 473 | 527 | -54 |
| 1978-08-22 | vs SFN | 125 | L 4-7 | 50-75 | 6 | 15,937 | Nino Espinosa | Ed Halicki | Ed Halicki | Nino Espinosa | Randy Moffitt | 477 | 534 | -57 |
| 1978-08-23 | vs SFN | 126 | L 1-2 | 50-76 | 6 | 14,383 | Tom Hausman | Bob Knepper | Bob Knepper | Skip Lockwood | Gary Lavelle | 478 | 536 | -58 |
| 1978-08-24 | @ SDN | 127 | W 6-3 | 51-76 | 6 | 17,613 | Mike Bruhert | Bob Owchinko | Mike Bruhert | Bob Owchinko | | 484 | 539 | -55 |
| 1978-08-25 | @ SDN | 128 | W 2-1 | 52-76 | 6 | 19,459 | Craig Swan | Gaylord Perry | Craig Swan | Gaylord Perry | | 486 | 540 | -54 |
| 1978-08-26 | @ SDN | 129 | L 1-2 | 52-77 | 6 | 16,458 | Jerry Koosman | Mickey Lolich | Mickey Lolich | Jerry Koosman | Rollie Fingers | 487 | 542 | -55 |
| 1978-08-27 | @ SDN | 130 | L 0-3 | 52-78 | 6 | 16,503 | Nino Espinosa | Eric Rasmussen | Eric Rasmussen | Nino Espinosa | | 487 | 545 | -58 |
| 1978-08-29 | @ SFN | 131 | L 0-2 | 52-79 | 6 | 34,174 | Tom Hausman | Bob Knepper | Bob Knepper | Tom Hausman | | 487 | 547 | -60 |
| 1978-08-30 | @ SFN | 132 | W 10-4 | 53-79 | 6 | 14,360 | Craig Swan | John Montefusco | Craig Swan | John Montefusco | | 497 | 551 | -54 |
| 1978-09-01 | @ LAN | 133 | L 3-4 | 53-80 | 6 | 33,292 | Jerry Koosman | Doug Rau | Terry Forster | Kevin Kobel | | 500 | 555 | -55 |
| 1978-09-02 | @ LAN | 134 | L 2-3 | 54-81 | 6 | 0 | Mike Bruhert | Burt Hooton | Burt Hooton | Mike Bruhert | | 502 | 558 | -56 |
| 1978-09-02 | @ LAN | 135 | W 5-3 | 54-81 | 6 | 49,818 | Nino Espinosa | Bob Welch | Dale Murray | Charlie Hough | | 507 | 561 | -54 |
| 1978-09-03 | @ LAN | 136 | W 8-5 | 55-81 | 6 | 26,983 | Tom Hausman | Tommy John | Tom Hausman | Tommy John | | 515 | 566 | -51 |
| 1978-09-04 | @ PIT | 137 | L 4-7 | 55-83 | 6 | 0 | Roy Lee Jackson | Jim Rooker | Ed Whitson | Skip Lockwood | Grant Jackson | 519 | 573 | -54 |
| 1978-09-04 | @ PIT | 138 | L 0-7 | 55-83 | 6 | 25,765 | Juan Berenguer | Jim Bibby | Jim Bibby | Juan Berenguer | | 519 | 580 | -61 |
| 1978-09-05 | @ PIT | 139 | L 0-8 | 55-84 | 6 | 18,476 | Jerry Koosman | Jerry Reuss | Jerry Reuss | Jerry Koosman | | 519 | 588 | -69 |
| 1978-09-06 | @ MON | 140 | L 2-8 | 55-85 | 6 | 7,894 | Mike Bruhert | Ross Grimsley | Ross Grimsley | Mike Bruhert | | 521 | 596 | -75 |
| 1978-09-07 | @ MON | 141 | W 9-4 | 56-85 | 6 | 10,161 | Nino Espinosa | Bob James | Nino Espinosa | Bob James | | 530 | 600 | -70 |
| 1978-09-08 | vs PIT | 142 | W 3-2 | 57-85 | 6 | 4,749 | Tom Hausman | Bert Blyleven | Dale Murray | Bert Blyleven | | 533 | 602 | -69 |
| 1978-09-09 | vs PIT | 143 | W 4-1 | 58-85 | 6 | 8,881 | Kevin Kobel | Jim Rooker | Kevin Kobel | Jim Rooker | | 537 | 603 | -66 |
| 1978-09-10 | vs PIT | 144 | W 11-9 | 59-85 | 6 | 9,256 | Jerry Koosman | Jerry Reuss | Dwight Bernard | Kent Tekulve | Mardie Cornejo | 548 | 612 | -64 |
| 1978-09-11 | vs CHN | 145 | L 4-9 | 59-86 | 6 | 4,096 | Mike Bruhert | Dennis Lamp | Dennis Lamp | Mike Bruhert | | 552 | 621 | -69 |
| 1978-09-13 | vs MON | 146 | L 3-4 | 59-87 | 6 | 4,302 | Nino Espinosa | Scott Sanderson | Scott Sanderson | Nino Espinosa | Mike Garman | 555 | 625 | -70 |
| 1978-09-14 | vs MON | 147 | W 7-6 | 60-87 | 6 | 3,710 | Kevin Kobel | Dan Schatzeder | Mardie Cornejo | Randy Miller | Dale Murray | 562 | 631 | -69 |
| 1978-09-15 | @ PHI | 148 | W 5-4 | 61-87 | 6 | 29,257 | Jerry Koosman | Jim Kaat | Dale Murray | Tug McGraw | | 567 | 635 | -68 |
| 1978-09-16 | @ PHI | 149 | L 1-2 | 61-88 | 6 | 44,307 | Craig Swan | Steve Carlton | Steve Carlton | Dwight Bernard | | 568 | 637 | -69 |
| 1978-09-17 | @ PHI | 150 | W 2-0 | 62-88 | 6 | 35,301 | Mike Bruhert | Larry Christenson | Mike Bruhert | Larry Christenson | | 570 | 637 | -67 |
| 1978-09-19 | @ SLN | 151 | L 3-5 | 62-89 | 6 | 5,257 | Nino Espinosa | Tom Bruno | Mark Littell | Dale Murray | | 573 | 642 | -69 |
| 1978-09-20 | @ SLN | 152 | W 7-6 | 63-89 | 6 | 6,030 | Kevin Kobel | Dan O'Brien | Kevin Kobel | George Frazier | Jerry Koosman | 580 | 648 | -68 |
| 1978-09-21 | @ SLN | 153 | L 2-6 | 63-90 | 6 | 3,912 | Craig Swan | John Urrea | John Urrea | Craig Swan | | 582 | 654 | -72 |
| 1978-09-23 | vs PHI | 154 | L 0-1 | 63-92 | 6 | 0 | Mike Bruhert | Larry Christenson | Larry Christenson | Mike Bruhert | | 582 | 655 | -73 |
| 1978-09-23 | vs PHI | 155 | L 3-6 | 63-92 | 6 | 9,694 | Roy Lee Jackson | Dick Ruthven | Dick Ruthven | Dwight Bernard | | 585 | 661 | -76 |
| 1978-09-24 | vs PHI | 156 | L 2-8 | 63-93 | 6 | 25,473 | Nino Espinosa | Steve Carlton | Steve Carlton | Nino Espinosa | | 587 | 669 | -82 |
| 1978-09-25 | vs SLN | 157 | L 0-3 | 63-94 | 6 | 3,697 | Kevin Kobel | Silvio Martinez | Silvio Martinez | Kevin Kobel | | 587 | 672 | -85 |
| 1978-09-26 | vs SLN | 158 | W 3-1 | 64-94 | 6 | 3,698 | Craig Swan | Rob Dressler | Craig Swan | Rob Dressler | Dale Murray | 590 | 673 | -83 |
| 1978-09-29 | @ CHN | 159 | W 3-2 | 65-95 | 6 | 0 | Nino Espinosa | Rick Reuschel | Nino Espinosa | Rick Reuschel | Jerry Koosman | 593 | 675 | -82 |
| 1978-09-29 | @ CHN | 160 | L 4-5 | 65-95 | 6 | 3,333 | Mike Bruhert | Mike Krukow | Mike Krukow | Mike Bruhert | Bruce Sutter | 597 | 680 | -83 |
| 1978-09-30 | @ CHN | 161 | L 5-7 | 65-96 | 6 | 16,504 | Juan Berenguer | Dennis Lamp | Manny Seoane | Dwight Bernard | Ken Holtzman | 602 | 687 | -85 |
| 1978-10-01 | @ CHN | 162 | W 5-3 | 66-96 | 6 | 11,617 | Kevin Kobel | Lynn McGlothen | Kevin Kobel | Lynn McGlothen | Dale Murray | 607 | 690 | -83 |