| 1978-04-07 | vs SLN | 1 | L 1-5 | 0-1 | 6 | 47,791 | Steve Carlton | Bob Forsch | Bob Forsch | Steve Carlton | | 1 | 5 | -4 |
| 1978-04-08 | vs SLN | 2 | W 7-0 | 1-1 | 3 | 24,441 | Larry Christenson | Eric Rasmussen | Larry Christenson | Eric Rasmussen | | 8 | 5 | 3 |
| 1978-04-09 | vs SLN | 3 | W 12-3 | 2-1 | 2 | 35,104 | Randy Lerch | John Urrea | Randy Lerch | John Urrea | | 20 | 8 | 12 |
| 1978-04-12 | vs MON | 4 | L 7-8 | 2-2 | 4 | 19,110 | Jim Lonborg | Steve Rogers | Steve Rogers | Jim Lonborg | Bill Atkinson | 27 | 16 | 11 |
| 1978-04-14 | @ SLN | 5 | W 4-3 | 3-2 | 2 | 17,921 | Steve Carlton | Mark Littell | Steve Carlton | Pete Vuckovich | Tug McGraw | 31 | 19 | 12 |
| 1978-04-15 | @ SLN | 6 | W 3-2 | 4-2 | 1 | 13,844 | Larry Christenson | John Denny | Tug McGraw | Pete Vuckovich | | 34 | 21 | 13 |
| 1978-04-16 | @ SLN | 7 | L 0-5 | 4-3 | 1 | 11,495 | Randy Lerch | Bob Forsch | Bob Forsch | Randy Lerch | | 34 | 26 | 8 |
| 1978-04-17 | @ PIT | 8 | W 6-2 | 5-3 | 1 | 7,343 | Jim Lonborg | John Candelaria | Jim Lonborg | John Candelaria | | 40 | 28 | 12 |
| 1978-04-22 | @ MON | 9 | L 3-7 | 5-5 | 4 | 0 | Steve Carlton | Wayne Twitchell | Wayne Twitchell | Steve Carlton | Stan Bahnsen | 43 | 35 | 8 |
| 1978-04-22 | @ MON | 10 | L 3-5 | 5-5 | 4 | 19,237 | Larry Christenson | Ross Grimsley | Ross Grimsley | Larry Christenson | Stan Bahnsen | 46 | 40 | 6 |
| 1978-04-23 | @ MON | 11 | L 2-5 | 5-6 | 5 | 17,922 | Jim Lonborg | Steve Rogers | Steve Rogers | Jim Lonborg | Darold Knowles | 48 | 45 | 3 |
| 1978-04-24 | vs CHN | 12 | W 12-2 | 6-6 | 4 | 20,115 | Randy Lerch | Woodie Fryman | Randy Lerch | Woodie Fryman | | 60 | 47 | 13 |
| 1978-04-25 | vs CHN | 13 | W 7-0 | 7-6 | 2 | 17,227 | Jim Kaat | Dennis Lamp | Jim Kaat | Dennis Lamp | | 67 | 47 | 20 |
| 1978-04-26 | vs CHN | 14 | L 2-4 | 7-7 | 4 | 17,299 | Steve Carlton | Rick Reuschel | Rick Reuschel | Steve Carlton | Bruce Sutter | 69 | 51 | 18 |
| 1978-04-28 | vs SDN | 15 | W 3-2 | 8-7 | 3 | 26,872 | Larry Christenson | Bob Owchinko | Larry Christenson | Bob Owchinko | Ron Reed | 72 | 53 | 19 |
| 1978-04-29 | vs SDN | 16 | W 7-2 | 9-7 | 1 | 28,390 | Jim Lonborg | Dave Freisleben | Jim Lonborg | Dave Freisleben | | 79 | 55 | 24 |
| 1978-04-30 | vs SDN | 17 | W 11-4 | 10-7 | 1 | 31,101 | Randy Lerch | Randy Jones | Randy Lerch | Randy Jones | | 90 | 59 | 31 |
| 1978-05-01 | @ CIN | 18 | W 12-1 | 11-7 | 1 | 21,476 | Steve Carlton | Tom Seaver | Steve Carlton | Tom Seaver | | 102 | 60 | 42 |
| 1978-05-03 | @ CIN | 19 | L 3-12 | 11-8 | 2 | 26,054 | Larry Christenson | Fred Norman | Fred Norman | Larry Christenson | | 105 | 72 | 33 |
| 1978-05-05 | vs NYN | 20 | W 9-4 | 12-8 | 2 | 22,116 | Jim Lonborg | Nino Espinosa | Jim Lonborg | Nino Espinosa | Tug McGraw | 114 | 76 | 38 |
| 1978-05-06 | vs NYN | 21 | W 7-2 | 13-8 | 1 | 22,250 | Steve Carlton | Pat Zachry | Steve Carlton | Pat Zachry | | 121 | 78 | 43 |
| 1978-05-07 | vs NYN | 22 | W 8-5 | 14-8 | 1 | 39,106 | Randy Lerch | Craig Swan | Gene Garber | Craig Swan | Tug McGraw | 129 | 83 | 46 |
| 1978-05-09 | vs HOU | 23 | L 1-5 | 14-9 | 1 | 18,144 | Larry Christenson | J.R. Richard | J.R. Richard | Larry Christenson | | 130 | 88 | 42 |
| 1978-05-10 | vs HOU | 24 | W 3-1 | 15-9 | 1 | 20,096 | Jim Lonborg | Mark Lemongello | Jim Lonborg | Mark Lemongello | | 133 | 89 | 44 |
| 1978-05-11 | vs CIN | 25 | W 4-1 | 16-9 | 1 | 32,580 | Steve Carlton | Tom Seaver | Steve Carlton | Tom Seaver | | 137 | 90 | 47 |
| 1978-05-12 | vs CIN | 26 | L 0-3 | 16-10 | 1 | 38,179 | Randy Lerch | Bill Bonham | Bill Bonham | Randy Lerch | Paul Moskau | 137 | 93 | 44 |
| 1978-05-13 | vs CIN | 27 | L 3-4 | 16-11 | 1 | 35,802 | Jim Kaat | Fred Norman | Manny Sarmiento | Tug McGraw | | 140 | 97 | 43 |
| 1978-05-14 | vs CIN | 28 | W 7-4 | 17-11 | 1 | 30,482 | Larry Christenson | Tom Hume | Larry Christenson | Tom Hume | Ron Reed | 147 | 101 | 46 |
| 1978-05-15 | @ HOU | 29 | L 0-5 | 17-12 | 1 | 9,943 | Jim Lonborg | J.R. Richard | J.R. Richard | Jim Lonborg | | 147 | 106 | 41 |
| 1978-05-16 | @ HOU | 30 | L 1-6 | 17-13 | 1 | 11,381 | Steve Carlton | Mark Lemongello | Mark Lemongello | Steve Carlton | | 148 | 112 | 36 |
| 1978-05-17 | @ HOU | 31 | L 1-2 | 17-14 | 1 | 11,856 | Randy Lerch | Joaquin Andujar | Joaquin Andujar | Randy Lerch | Tom Dixon | 149 | 114 | 35 |
| 1978-05-18 | @ HOU | 32 | W 8-5 | 18-14 | 1 | 10,828 | Larry Christenson | Joe Niekro | Gene Garber | Joe Sambito | | 157 | 119 | 38 |
| 1978-05-19 | @ NYN | 33 | L 3-4 | 18-15 | 1 | 13,181 | Jim Kaat | Craig Swan | Skip Lockwood | Tug McGraw | | 160 | 123 | 37 |
| 1978-05-20 | @ NYN | 34 | W 9-4 | 19-15 | 1 | 14,110 | Steve Carlton | Mike Bruhert | Tug McGraw | Dale Murray | | 169 | 127 | 42 |
| 1978-05-21 | @ NYN | 35 | L 5-6 | 19-16 | 1 | 18,183 | Randy Lerch | Jerry Koosman | Skip Lockwood | Tug McGraw | | 174 | 133 | 41 |
| 1978-05-24 | @ CHN | 36 | L 4-6 | 19-17 | 2 | 17,901 | Jim Kaat | Ray Burris | Bruce Sutter | Gene Garber | | 178 | 139 | 39 |
| 1978-05-25 | @ CHN | 37 | L 1-5 | 19-18 | 2 | 19,788 | Steve Carlton | Rick Reuschel | Rick Reuschel | Steve Carlton | Bruce Sutter | 179 | 144 | 35 |
| 1978-05-26 | @ ATL | 38 | L 2-4 | 19-19 | 3 | 16,638 | Randy Lerch | Phil Niekro | Phil Niekro | Randy Lerch | | 181 | 148 | 33 |
| 1978-05-27 | @ ATL | 39 | W 6-5 | 20-19 | 2 | 15,081 | Jim Lonborg | Dick Ruthven | Tug McGraw | Rick Camp | Gene Garber | 187 | 153 | 34 |
| 1978-05-28 | @ ATL | 40 | L 3-5 | 20-20 | 3 | 22,233 | Larry Christenson | Preston Hanna | Preston Hanna | Larry Christenson | Jamie Easterly | 190 | 158 | 32 |
| 1978-05-29 | vs PIT | 41 | W 4-3 | 21-20 | 2 | 34,353 | Jim Kaat | Don Robinson | Warren Brusstar | Dave Hamilton | | 194 | 161 | 33 |
| 1978-05-30 | vs PIT | 42 | W 6-1 | 22-20 | 2 | 26,123 | Steve Carlton | Bert Blyleven | Steve Carlton | Bert Blyleven | | 200 | 162 | 38 |
| 1978-05-31 | vs PIT | 43 | L 1-2 | 22-21 | 3 | 29,595 | Randy Lerch | John Candelaria | John Candelaria | Randy Lerch | Kent Tekulve | 201 | 164 | 37 |
| 1978-06-02 | vs LAN | 44 | W 4-2 | 23-21 | 2 | 42,347 | Jim Lonborg | Burt Hooton | Jim Lonborg | Burt Hooton | Gene Garber | 205 | 166 | 39 |
| 1978-06-03 | vs LAN | 45 | W 5-1 | 24-21 | 2 | 31,442 | Larry Christenson | Don Sutton | Tug McGraw | Terry Forster | | 210 | 167 | 43 |
| 1978-06-04 | vs LAN | 46 | W 9-4 | 25-21 | 2 | 42,066 | Jim Kaat | Tommy John | Jim Kaat | Tommy John | | 219 | 171 | 48 |
| 1978-06-05 | vs SFN | 47 | W 4-3 | 26-21 | 2 | 37,684 | Steve Carlton | Vida Blue | Steve Carlton | Vida Blue | Ron Reed | 223 | 174 | 49 |
| 1978-06-06 | vs SFN | 48 | W 7-6 | 27-21 | 2 | 28,093 | Randy Lerch | John Montefusco | Tug McGraw | Gary Lavelle | | 230 | 180 | 50 |
| 1978-06-07 | vs SFN | 49 | W 5-4 | 28-21 | 2 | 20,708 | Jim Lonborg | Ed Halicki | Tug McGraw | Randy Moffitt | | 235 | 184 | 51 |
| 1978-06-09 | vs ATL | 50 | W 6-1 | 29-21 | 2 | 40,272 | Larry Christenson | Eddie Solomon | Larry Christenson | Eddie Solomon | | 241 | 185 | 56 |
| 1978-06-10 | vs ATL | 51 | W 6-2 | 30-21 | 1 | 33,292 | Jim Kaat | Dick Ruthven | Jim Kaat | Dick Ruthven | Gene Garber | 247 | 187 | 60 |
| 1978-06-11 | vs ATL | 52 | L 0-4 | 30-22 | 2 | 58,367 | Steve Carlton | Phil Niekro | Phil Niekro | Steve Carlton | | 247 | 191 | 56 |
| 1978-06-12 | @ LAN | 53 | L 5-6 | 30-23 | 2 | 26,604 | Jim Lonborg | Burt Hooton | Burt Hooton | Jim Lonborg | Lance Rautzhan | 252 | 197 | 55 |
| 1978-06-13 | @ LAN | 54 | L 3-5 | 30-24 | 2 | 41,257 | Randy Lerch | Don Sutton | Don Sutton | Randy Lerch | | 255 | 202 | 53 |
| 1978-06-14 | @ SFN | 55 | L 1-2 | 30-25 | 2 | 13,902 | Larry Christenson | Vida Blue | Vida Blue | Larry Christenson | Randy Moffitt | 256 | 204 | 52 |
| 1978-06-15 | @ SFN | 56 | L 1-6 | 30-26 | 2 | 14,754 | Jim Kaat | John Montefusco | John Montefusco | Jim Kaat | | 257 | 210 | 47 |
| 1978-06-16 | @ SDN | 57 | W 5-0 | 31-26 | 2 | 21,124 | Steve Carlton | Randy Jones | Steve Carlton | Randy Jones | | 262 | 210 | 52 |
| 1978-06-17 | @ SDN | 58 | L 0-7 | 31-27 | 2 | 27,319 | Jim Lonborg | Bob Owchinko | Bob Owchinko | Jim Lonborg | | 262 | 217 | 45 |
| 1978-06-18 | @ SDN | 59 | L 1-4 | 31-28 | 2 | 21,195 | Dick Ruthven | Gaylord Perry | Gaylord Perry | Dick Ruthven | Rollie Fingers | 263 | 221 | 42 |
| 1978-06-20 | vs SLN | 60 | L 2-4 | 31-29 | 2 | 30,119 | Larry Christenson | Bob Forsch | Bob Forsch | Larry Christenson | Mark Littell | 265 | 225 | 40 |
| 1978-06-22 | vs SLN | 61 | W 2-1 | 32-29 | 2 | 29,183 | Steve Carlton | John Denny | Steve Carlton | John Denny | | 267 | 226 | 41 |
| 1978-06-23 | vs CHN | 62 | W 6-1 | 34-29 | 1 | 0 | Dick Ruthven | Dave Roberts | Dick Ruthven | Dave Roberts | | 273 | 227 | 46 |
| 1978-06-23 | vs CHN | 63 | W 6-1 | 34-29 | 1 | 45,234 | Jim Lonborg | Dennis Lamp | Jim Lonborg | Dennis Lamp | | 279 | 228 | 51 |
| 1978-06-24 | vs CHN | 64 | W 6-2 | 35-29 | 1 | 41,605 | Jim Kaat | Ken Holtzman | Jim Kaat | Ken Holtzman | Ron Reed | 285 | 230 | 55 |
| 1978-06-25 | vs CHN | 65 | W 4-2 | 36-29 | 1 | 36,075 | Larry Christenson | Rick Reuschel | Larry Christenson | Rick Reuschel | | 289 | 232 | 57 |
| 1978-06-26 | @ MON | 66 | L 1-5 | 36-30 | 1 | 19,487 | Steve Carlton | Steve Rogers | Steve Rogers | Steve Carlton | | 290 | 237 | 53 |
| 1978-06-27 | @ MON | 67 | W 1-0 | 37-30 | 1 | 36,885 | Dick Ruthven | Hal Dues | Dick Ruthven | Hal Dues | | 291 | 237 | 54 |
| 1978-06-28 | @ MON | 68 | W 7-5 | 38-30 | 1 | 35,182 | Jim Lonborg | Dan Schatzeder | Jim Lonborg | Mike Garman | Tug McGraw | 298 | 242 | 56 |
| 1978-06-29 | @ CHN | 69 | W 9-3 | 39-30 | 1 | 25,669 | Jim Kaat | Dave Roberts | Jim Kaat | Dave Roberts | Tug McGraw | 307 | 245 | 62 |
| 1978-06-30 | @ CHN | 70 | L 0-2 | 40-31 | 1 | 0 | Larry Christenson | Mike Krukow | Mike Krukow | Larry Christenson | | 307 | 247 | 60 |
| 1978-06-30 | @ CHN | 71 | W 6-5 | 40-31 | 1 | 29,525 | Steve Carlton | Ray Burris | Tug McGraw | Bruce Sutter | | 313 | 252 | 61 |
| 1978-07-01 | @ CHN | 72 | W 2-1 | 41-31 | 1 | 26,042 | Randy Lerch | Dennis Lamp | Randy Lerch | Dennis Lamp | Ron Reed | 315 | 253 | 62 |
| 1978-07-02 | @ CHN | 73 | W 6-5 | 42-31 | 1 | 25,934 | Dick Ruthven | Ken Holtzman | Dick Ruthven | Ken Holtzman | Tug McGraw | 321 | 258 | 63 |
| 1978-07-04 | @ NYN | 74 | L 0-4 | 43-32 | 1 | 0 | Larry Christenson | Pat Zachry | Pat Zachry | Larry Christenson | | 321 | 262 | 59 |
| 1978-07-04 | @ NYN | 75 | W 3-2 | 43-32 | 1 | 10,410 | Jim Lonborg | Craig Swan | Rawly Eastwick | Craig Swan | Ron Reed | 324 | 264 | 60 |
| 1978-07-05 | @ NYN | 76 | W 7-5 | 44-32 | 1 | 8,667 | Steve Carlton | Jerry Koosman | Warren Brusstar | Jerry Koosman | Tug McGraw | 331 | 269 | 62 |
| 1978-07-06 | vs MON | 77 | W 7-6 | 45-32 | 1 | 50,149 | Jim Kaat | Ross Grimsley | Rawly Eastwick | Ross Grimsley | | 338 | 275 | 63 |
| 1978-07-07 | vs MON | 78 | L 4-7 | 45-33 | 1 | 45,193 | Dick Ruthven | Steve Rogers | Steve Rogers | Dick Ruthven | Mike Garman | 342 | 282 | 60 |
| 1978-07-08 | vs MON | 79 | W 6-3 | 46-34 | 1 | 0 | Larry Christenson | Woodie Fryman | Larry Christenson | Woodie Fryman | Ron Reed | 348 | 285 | 63 |
| 1978-07-08 | vs MON | 80 | L 1-8 | 46-34 | 1 | 50,098 | Jim Lonborg | Hal Dues | Hal Dues | Jim Lonborg | | 349 | 293 | 56 |
| 1978-07-09 | vs MON | 81 | W 8-7 | 47-34 | 1 | 40,949 | Steve Carlton | Dan Schatzeder | Tug McGraw | Darold Knowles | | 357 | 300 | 57 |
| 1978-07-14 | @ ATL | 82 | L 2-7 | 47-35 | 1 | 17,464 | Steve Carlton | Phil Niekro | Phil Niekro | Steve Carlton | | 359 | 307 | 52 |
| 1978-07-15 | @ ATL | 83 | L 2-3 | 47-36 | 1 | 0 | Jim Kaat | Rick Camp | Rick Camp | Jim Kaat | Gene Garber | 361 | 310 | 51 |
| 1978-07-16 | @ ATL | 84 | W 4-2 | 48-36 | 1 | 20,734 | Dick Ruthven | Preston Hanna | Dick Ruthven | Preston Hanna | Ron Reed | 365 | 312 | 53 |
| 1978-07-17 | @ HOU | 85 | L 1-2 | 48-37 | 1 | 14,397 | Larry Christenson | Joe Niekro | Joe Niekro | Rawly Eastwick | | 366 | 314 | 52 |
| 1978-07-18 | @ HOU | 86 | L 1-9 | 48-38 | 1 | 15,478 | Jim Lonborg | J.R. Richard | J.R. Richard | Jim Lonborg | | 367 | 323 | 44 |
| 1978-07-19 | vs CIN | 87 | L 2-7 | 48-39 | 1 | 45,608 | Steve Carlton | Paul Moskau | Dave Tomlin | Steve Carlton | Doug Bair | 369 | 330 | 39 |
| 1978-07-20 | vs CIN | 88 | W 8-6 | 49-39 | 1 | 44,054 | Jim Kaat | Tom Hume | Warren Brusstar | Manny Sarmiento | Tug McGraw | 377 | 336 | 41 |
| 1978-07-21 | vs HOU | 89 | W 6-1 | 51-39 | 1 | 0 | Dick Ruthven | Joe Niekro | Dick Ruthven | Joe Niekro | | 383 | 337 | 46 |
| 1978-07-21 | vs HOU | 90 | W 8-2 | 51-39 | 1 | 35,389 | Larry Christenson | Rick Williams | Larry Christenson | Rick Williams | | 391 | 339 | 52 |
| 1978-07-22 | vs HOU | 91 | W 3-2 | 52-39 | 1 | 33,672 | Randy Lerch | J.R. Richard | Ron Reed | Ken Forsch | | 394 | 341 | 53 |
| 1978-07-23 | vs HOU | 92 | W 13-2 | 53-39 | 1 | 30,554 | Steve Carlton | Tom Dixon | Steve Carlton | Tom Dixon | | 407 | 343 | 64 |
| 1978-07-24 | vs ATL | 93 | L 1-5 | 53-40 | 1 | 30,184 | Jim Lonborg | Eddie Solomon | Eddie Solomon | Jim Lonborg | Craig Skok | 408 | 348 | 60 |
| 1978-07-25 | vs ATL | 94 | L 0-4 | 53-41 | 1 | 25,954 | Larry Christenson | Tommy Boggs | Tommy Boggs | Larry Christenson | | 408 | 352 | 56 |
| 1978-07-26 | vs ATL | 95 | L 2-4 | 53-42 | 1 | 50,218 | Jim Kaat | Phil Niekro | Phil Niekro | Jim Kaat | | 410 | 356 | 54 |
| 1978-07-28 | @ CIN | 96 | W 12-2 | 54-43 | 1 | 0 | Randy Lerch | Fred Norman | Randy Lerch | Fred Norman | | 422 | 358 | 64 |
| 1978-07-28 | @ CIN | 97 | L 1-2 | 54-43 | 1 | 51,779 | Steve Carlton | Tom Seaver | Tom Seaver | Steve Carlton | Doug Bair | 423 | 360 | 63 |
| 1978-07-29 | @ CIN | 98 | L 2-6 | 54-44 | 1 | 49,108 | Jim Lonborg | Paul Moskau | Paul Moskau | Jim Lonborg | | 425 | 366 | 59 |
| 1978-07-30 | @ CIN | 99 | L 3-5 | 54-45 | 1 | 44,092 | Larry Christenson | Tom Hume | Tom Hume | Larry Christenson | Doug Bair | 428 | 371 | 57 |
| 1978-07-31 | vs NYN | 100 | W 6-1 | 55-45 | 1 | 21,133 | Dick Ruthven | Nino Espinosa | Dick Ruthven | Nino Espinosa | | 434 | 372 | 62 |
| 1978-08-01 | vs NYN | 101 | L 1-5 | 55-46 | 1 | 31,085 | Steve Carlton | Tom Hausman | Kevin Kobel | Steve Carlton | | 435 | 377 | 58 |
| 1978-08-02 | vs NYN | 102 | W 8-6 | 56-46 | 1 | 32,382 | Randy Lerch | Jerry Koosman | Randy Lerch | Jerry Koosman | Tug McGraw | 443 | 383 | 60 |
| 1978-08-04 | @ PIT | 103 | W 2-0 | 57-47 | 1 | 0 | Larry Christenson | Jim Rooker | Larry Christenson | Jim Rooker | | 445 | 383 | 62 |
| 1978-08-04 | @ PIT | 104 | L 2-5 | 57-47 | 1 | 30,865 | Jim Kaat | Don Robinson | Don Robinson | Jim Kaat | | 447 | 388 | 59 |
| 1978-08-06 | @ PIT | 105 | W 3-2 | 59-47 | 1 | 0 | Dick Ruthven | Bert Blyleven | Dick Ruthven | Bert Blyleven | | 450 | 390 | 60 |
| 1978-08-06 | @ PIT | 106 | W 5-0 | 59-47 | 1 | 31,141 | Steve Carlton | Jim Bibby | Steve Carlton | Jim Bibby | | 455 | 390 | 65 |
| 1978-08-07 | @ SLN | 107 | L 3-6 | 59-48 | 1 | 18,671 | Randy Lerch | Aurelio Lopez | Aurelio Lopez | Randy Lerch | Mark Littell | 458 | 396 | 62 |
| 1978-08-08 | @ SLN | 108 | L 0-2 | 59-50 | 1 | 0 | Larry Christenson | Pete Vuckovich | Pete Vuckovich | Larry Christenson | | 458 | 398 | 60 |
| 1978-08-08 | @ SLN | 109 | L 2-6 | 59-50 | 1 | 26,880 | Jim Lonborg | Tom Bruno | Tom Bruno | Jim Lonborg | | 460 | 404 | 56 |
| 1978-08-09 | @ SLN | 110 | W 6-3 | 60-50 | 1 | 16,172 | Jim Kaat | Bob Forsch | Jim Kaat | Bob Forsch | Ron Reed | 466 | 407 | 59 |
| 1978-08-10 | vs PIT | 111 | W 3-1 | 61-50 | 1 | 34,672 | Dick Ruthven | Bert Blyleven | Dick Ruthven | Bert Blyleven | | 469 | 408 | 61 |
| 1978-08-11 | vs PIT | 112 | W 15-4 | 62-50 | 1 | 35,101 | Steve Carlton | Bruce Kison | Steve Carlton | Bruce Kison | | 484 | 412 | 72 |
| 1978-08-12 | vs PIT | 113 | W 10-1 | 63-50 | 1 | 30,110 | Randy Lerch | Jim Bibby | Randy Lerch | Jim Bibby | | 494 | 413 | 81 |
| 1978-08-13 | vs PIT | 114 | L 3-7 | 63-51 | 1 | 38,119 | Larry Christenson | Don Robinson | Don Robinson | Larry Christenson | | 497 | 420 | 77 |
| 1978-08-15 | vs LAN | 115 | L 4-5 | 63-52 | 1 | 38,386 | Dick Ruthven | Doug Rau | Doug Rau | Dick Ruthven | Lance Rautzhan | 501 | 425 | 76 |
| 1978-08-16 | vs LAN | 116 | L 2-5 | 63-53 | 1 | 37,660 | Jim Kaat | Bob Welch | Bob Welch | Jim Kaat | | 503 | 430 | 73 |
| 1978-08-17 | vs LAN | 117 | L 2-5 | 63-54 | 1 | 36,325 | Randy Lerch | Burt Hooton | Burt Hooton | Tug McGraw | Terry Forster | 505 | 435 | 70 |
| 1978-08-18 | vs SFN | 118 | L 5-6 | 63-55 | 1 | 36,554 | Larry Christenson | Bob Knepper | Gary Lavelle | Tug McGraw | | 510 | 441 | 69 |
| 1978-08-19 | vs SFN | 119 | W 3-0 | 64-55 | 1 | 54,288 | Steve Carlton | John Montefusco | Steve Carlton | John Montefusco | | 513 | 441 | 72 |
| 1978-08-20 | vs SFN | 120 | W 5-3 | 65-55 | 1 | 51,088 | Dick Ruthven | Jim Barr | Dick Ruthven | Jim Barr | Ron Reed | 518 | 444 | 74 |
| 1978-08-21 | vs SDN | 121 | L 3-7 | 65-56 | 1 | 27,124 | Randy Lerch | Gaylord Perry | Gaylord Perry | Warren Brusstar | Bob Shirley | 521 | 451 | 70 |
| 1978-08-22 | vs SDN | 122 | W 5-3 | 66-56 | 1 | 36,339 | Larry Christenson | Eric Rasmussen | Larry Christenson | Eric Rasmussen | Ron Reed | 526 | 454 | 72 |
| 1978-08-23 | vs SDN | 123 | L 5-6 | 66-57 | 1 | 31,032 | Jim Kaat | Randy Jones | Rollie Fingers | Ron Reed | | 531 | 460 | 71 |
| 1978-08-24 | @ LAN | 124 | L 4-5 | 66-58 | 1 | 49,064 | Steve Carlton | Tommy John | Tommy John | Warren Brusstar | Charlie Hough | 535 | 465 | 70 |
| 1978-08-25 | @ LAN | 125 | L 5-6 | 66-59 | 1 | 46,548 | Dick Ruthven | Don Sutton | Lance Rautzhan | Ron Reed | | 540 | 471 | 69 |
| 1978-08-26 | @ LAN | 126 | W 3-1 | 67-59 | 1 | 50,194 | Randy Lerch | Doug Rau | Randy Lerch | Doug Rau | | 543 | 472 | 71 |
| 1978-08-27 | @ LAN | 127 | W 9-3 | 68-59 | 1 | 43,065 | Larry Christenson | Bob Welch | Larry Christenson | Bob Welch | | 552 | 475 | 77 |
| 1978-08-28 | @ SDN | 128 | W 6-1 | 69-59 | 1 | 33,768 | Jim Kaat | Randy Jones | Jim Kaat | Randy Jones | | 558 | 476 | 82 |
| 1978-08-29 | @ SDN | 129 | W 9-5 | 70-59 | 1 | 13,568 | Dick Ruthven | Bob Owchinko | Dick Ruthven | Bob Owchinko | | 567 | 481 | 86 |
| 1978-08-30 | @ SDN | 130 | W 6-5 | 71-59 | 1 | 15,941 | Randy Lerch | Gaylord Perry | Warren Brusstar | Rollie Fingers | | 573 | 486 | 87 |
| 1978-09-01 | @ SFN | 131 | L 3-4 | 71-60 | 1 | 16,413 | Steve Carlton | Jim Barr | Gary Lavelle | Steve Carlton | | 576 | 490 | 86 |
| 1978-09-02 | @ SFN | 132 | W 3-1 | 72-60 | 1 | 27,457 | Larry Christenson | Vida Blue | Larry Christenson | Gary Lavelle | | 579 | 491 | 88 |
| 1978-09-03 | @ SFN | 133 | L 1-4 | 72-62 | 1 | 0 | Dick Ruthven | Bob Knepper | Bob Knepper | Dick Ruthven | | 580 | 495 | 85 |
| 1978-09-03 | @ SFN | 134 | L 2-3 | 72-62 | 1 | 39,596 | Jim Kaat | John Montefusco | John Montefusco | Warren Brusstar | John Curtis | 582 | 498 | 84 |
| 1978-09-04 | @ SLN | 135 | L 2-3 | 73-63 | 1 | 0 | Randy Lerch | Bob Forsch | Bob Forsch | Randy Lerch | Mark Littell | 584 | 501 | 83 |
| 1978-09-04 | @ SLN | 136 | W 10-2 | 73-63 | 1 | 19,015 | Jim Lonborg | Silvio Martinez | Jim Lonborg | Silvio Martinez | | 594 | 503 | 91 |
| 1978-09-06 | @ CHN | 137 | W 8-1 | 74-63 | 1 | 14,269 | Steve Carlton | Rick Reuschel | Steve Carlton | Rick Reuschel | | 602 | 504 | 98 |
| 1978-09-07 | @ CHN | 138 | W 5-3 | 75-63 | 1 | 11,427 | Larry Christenson | Dennis Lamp | Warren Brusstar | Donnie Moore | Ron Reed | 607 | 507 | 100 |
| 1978-09-08 | vs SLN | 139 | W 1-0 | 77-63 | 1 | 0 | Dick Ruthven | Tom Bruno | Dick Ruthven | Tom Bruno | | 608 | 507 | 101 |
| 1978-09-08 | vs SLN | 140 | W 2-1 | 77-63 | 1 | 35,160 | Jim Kaat | Dan O'Brien | Ron Reed | Dan O'Brien | | 610 | 508 | 102 |
| 1978-09-09 | vs SLN | 141 | W 6-3 | 78-63 | 1 | 35,824 | Randy Lerch | Bob Forsch | Randy Lerch | Bob Forsch | | 616 | 511 | 105 |
| 1978-09-10 | vs SLN | 142 | L 6-8 | 78-64 | 1 | 33,106 | Jim Lonborg | Silvio Martinez | Mark Littell | Ron Reed | Buddy Schultz | 622 | 519 | 103 |
| 1978-09-11 | vs PIT | 143 | W 10-3 | 79-64 | 1 | 33,198 | Steve Carlton | Don Robinson | Steve Carlton | Don Robinson | | 632 | 522 | 110 |
| 1978-09-12 | vs PIT | 144 | L 1-5 | 79-65 | 1 | 31,355 | Larry Christenson | John Candelaria | John Candelaria | Larry Christenson | Kent Tekulve | 633 | 527 | 106 |
| 1978-09-13 | vs CHN | 145 | W 6-2 | 80-65 | 1 | 30,114 | Dick Ruthven | Ray Burris | Dick Ruthven | Ray Burris | | 639 | 529 | 110 |
| 1978-09-14 | vs CHN | 146 | W 11-5 | 81-65 | 1 | 20,037 | Randy Lerch | Rick Reuschel | Warren Brusstar | Rick Reuschel | Ron Reed | 650 | 534 | 116 |
| 1978-09-15 | vs NYN | 147 | L 4-5 | 81-66 | 1 | 29,257 | Jim Kaat | Jerry Koosman | Dale Murray | Tug McGraw | | 654 | 539 | 115 |
| 1978-09-16 | vs NYN | 148 | W 2-1 | 82-66 | 1 | 44,307 | Steve Carlton | Craig Swan | Steve Carlton | Dwight Bernard | | 656 | 540 | 116 |
| 1978-09-17 | vs NYN | 149 | L 0-2 | 82-67 | 1 | 35,301 | Larry Christenson | Mike Bruhert | Mike Bruhert | Larry Christenson | | 656 | 542 | 114 |
| 1978-09-19 | @ MON | 150 | L 2-5 | 82-68 | 1 | 9,429 | Dick Ruthven | Scott Sanderson | Scott Sanderson | Dick Ruthven | Mike Garman | 658 | 547 | 111 |
| 1978-09-20 | @ MON | 151 | W 4-2 | 83-68 | 1 | 9,298 | Randy Lerch | Dan Schatzeder | Randy Lerch | Dan Schatzeder | Ron Reed | 662 | 549 | 113 |
| 1978-09-23 | @ NYN | 152 | W 1-0 | 85-68 | 1 | 0 | Larry Christenson | Mike Bruhert | Larry Christenson | Mike Bruhert | | 663 | 549 | 114 |
| 1978-09-23 | @ NYN | 153 | W 6-3 | 85-68 | 1 | 9,694 | Dick Ruthven | Roy Lee Jackson | Dick Ruthven | Dwight Bernard | | 669 | 552 | 117 |
| 1978-09-24 | @ NYN | 154 | W 8-2 | 86-68 | 1 | 25,473 | Steve Carlton | Nino Espinosa | Steve Carlton | Nino Espinosa | | 677 | 554 | 123 |
| 1978-09-25 | vs MON | 155 | W 3-2 | 87-68 | 1 | 11,651 | Randy Lerch | Dan Schatzeder | Ron Reed | Stan Bahnsen | | 680 | 556 | 124 |
| 1978-09-26 | vs MON | 156 | W 5-3 | 88-69 | 1 | 0 | Jim Kaat | David Palmer | Jim Kaat | David Palmer | Ron Reed | 685 | 559 | 126 |
| 1978-09-26 | vs MON | 157 | L 0-3 | 88-69 | 1 | 29,506 | Tug McGraw | Rudy May | Rudy May | Tug McGraw | | 685 | 562 | 123 |
| 1978-09-27 | vs MON | 158 | W 5-4 | 89-69 | 1 | 27,410 | Larry Christenson | Ross Grimsley | Larry Christenson | Ross Grimsley | Ron Reed | 690 | 566 | 124 |
| 1978-09-29 | @ PIT | 159 | L 4-5 | 89-71 | 1 | 0 | Dick Ruthven | Bert Blyleven | Kent Tekulve | Ron Reed | | 694 | 571 | 123 |
| 1978-09-29 | @ PIT | 160 | L 1-2 | 89-71 | 1 | 45,134 | Steve Carlton | Bruce Kison | Kent Tekulve | Steve Carlton | | 695 | 573 | 122 |
| 1978-09-30 | @ PIT | 161 | W 10-8 | 90-71 | 1 | 28,905 | Randy Lerch | Don Robinson | Randy Lerch | Grant Jackson | Ron Reed | 705 | 581 | 124 |
| 1978-10-01 | @ PIT | 162 | L 3-5 | 90-72 | 1 | 30,224 | Jim Kaat | Odell Jones | Odell Jones | Kevin Saucier | Kent Tekulve | 708 | 586 | 122 |