| 1978-04-08 | @ CLE | 1 | L 5-8 | 0-1 | 7 | 52,433 | Dennis Leonard | Wayne Garland | Wayne Garland | Dennis Leonard | Mike Paxton | 5 | 8 | -3 |
| 1978-04-09 | @ CLE | 2 | W 5-4 | 1-1 | 4 | 7,473 | Steve Busby | Rick Wise | Steve Busby | Rick Wise | Steve Mingori | 10 | 12 | -2 |
| 1978-04-10 | vs BAL | 3 | W 4-2 | 2-1 | 3 | 38,194 | Paul Splittorff | Nelson Briles | Paul Splittorff | Nelson Briles | Al Hrabosky | 14 | 14 | 0 |
| 1978-04-12 | vs BAL | 4 | W 5-2 | 3-1 | 2 | 17,449 | Dennis Leonard | Mike Flanagan | Dennis Leonard | Mike Flanagan | Steve Mingori | 19 | 16 | 3 |
| 1978-04-14 | vs CLE | 5 | W 3-1 | 4-1 | 1 | 17,526 | Paul Splittorff | Rick Wise | Paul Splittorff | Rick Wise | Doug Bird | 22 | 17 | 5 |
| 1978-04-15 | vs CLE | 6 | W 6-5 | 5-1 | 1 | 18,110 | Steve Busby | Don Hood | Marty Pattin | Mike Paxton | Al Hrabosky | 28 | 22 | 6 |
| 1978-04-16 | vs CLE | 7 | W 2-1 | 6-1 | 1 | 17,655 | Dennis Leonard | Wayne Garland | Dennis Leonard | Wayne Garland | | 30 | 23 | 7 |
| 1978-04-17 | @ TOR | 8 | W 3-1 | 7-1 | 1 | 10,169 | Larry Gura | Jesse Jefferson | Larry Gura | Jesse Jefferson | Al Hrabosky | 33 | 24 | 9 |
| 1978-04-18 | @ TOR | 9 | W 5-0 | 8-1 | 1 | 10,218 | Paul Splittorff | Dave Lemanczyk | Paul Splittorff | Dave Lemanczyk | | 38 | 24 | 14 |
| 1978-04-21 | @ BAL | 10 | L 1-2 | 8-2 | 1 | 6,203 | Dennis Leonard | Jim Palmer | Jim Palmer | Dennis Leonard | Don Stanhouse | 39 | 26 | 13 |
| 1978-04-22 | @ BAL | 11 | W 5-3 | 9-2 | 1 | 7,277 | Paul Splittorff | Mike Flanagan | Paul Splittorff | Mike Flanagan | Al Hrabosky | 44 | 29 | 15 |
| 1978-04-23 | @ BAL | 12 | W 6-5 | 10-2 | 1 | 13,833 | Steve Busby | Dennis Martinez | Larry Gura | Tim Stoddard | Marty Pattin | 50 | 34 | 16 |
| 1978-04-24 | @ TEX | 13 | W 8-6 | 11-2 | 1 | 15,530 | Jim Colborn | Dock Ellis | Doug Bird | Reggie Cleveland | | 58 | 40 | 18 |
| 1978-04-25 | @ TEX | 14 | L 1-4 | 11-3 | 2 | 14,154 | Dennis Leonard | Fergie Jenkins | Fergie Jenkins | Dennis Leonard | | 59 | 44 | 15 |
| 1978-04-26 | vs TOR | 15 | L 1-3 | 11-4 | 2 | 19,545 | Paul Splittorff | Tom Underwood | Tom Murphy | Paul Splittorff | | 60 | 47 | 13 |
| 1978-04-27 | vs TOR | 16 | L 7-8 | 11-5 | 2 | 17,422 | Larry Gura | Jim Clancy | Balor Moore | Doug Bird | Mike Willis | 67 | 55 | 12 |
| 1978-04-28 | vs MIL | 17 | W 7-6 | 12-5 | 2 | 20,166 | Steve Busby | Lary Sorensen | Jim Colborn | Eduardo Rodriguez | Marty Pattin | 74 | 61 | 13 |
| 1978-04-29 | vs MIL | 18 | W 11-2 | 13-5 | 2 | 27,521 | Dennis Leonard | Jerry Augustine | Dennis Leonard | Jerry Augustine | | 85 | 63 | 22 |
| 1978-04-30 | vs MIL | 19 | W 3-0 | 14-5 | 2 | 19,827 | Rich Gale | Mike Caldwell | Rich Gale | Mike Caldwell | Steve Mingori | 88 | 63 | 25 |
| 1978-05-01 | @ NYA | 20 | L 4-8 | 14-6 | 2 | 17,340 | Paul Splittorff | Jim Beattie | Rawly Eastwick | Paul Splittorff | Sparky Lyle | 92 | 71 | 21 |
| 1978-05-02 | @ NYA | 21 | L 2-4 | 14-7 | 2 | 19,152 | Larry Gura | Catfish Hunter | Catfish Hunter | Larry Gura | Sparky Lyle | 94 | 75 | 19 |
| 1978-05-03 | @ NYA | 22 | L 5-6 | 14-8 | 2 | 21,230 | Dennis Leonard | Ed Figueroa | Ed Figueroa | Dennis Leonard | Rich Gossage | 99 | 81 | 18 |
| 1978-05-05 | @ MIL | 23 | L 0-9 | 14-9 | 3 | 10,435 | Jim Colborn | Mike Caldwell | Mike Caldwell | Jim Colborn | | 99 | 90 | 9 |
| 1978-05-06 | @ MIL | 24 | L 3-4 | 14-10 | 3 | 13,914 | Paul Splittorff | Lary Sorensen | Lary Sorensen | Doug Bird | | 102 | 94 | 8 |
| 1978-05-07 | @ MIL | 25 | W 8-6 | 15-10 | 3 | 10,887 | Rich Gale | Jerry Augustine | Rich Gale | Jerry Augustine | Steve Mingori | 110 | 100 | 10 |
| 1978-05-08 | @ BOS | 26 | L 4-8 | 15-11 | 3 | 25,891 | Dennis Leonard | Luis Tiant | Bob Stanley | Dennis Leonard | | 114 | 108 | 6 |
| 1978-05-09 | @ BOS | 27 | L 3-4 | 15-12 | 3 | 22,369 | Jim Colborn | Dennis Eckersley | Dennis Eckersley | Jim Colborn | | 117 | 112 | 5 |
| 1978-05-12 | vs NYA | 28 | W 4-3 | 16-12 | 3 | 33,061 | Paul Splittorff | Ed Figueroa | Doug Bird | Rich Gossage | | 121 | 115 | 6 |
| 1978-05-13 | vs NYA | 29 | L 2-5 | 16-13 | 3 | 40,903 | Dennis Leonard | Ron Guidry | Ron Guidry | Dennis Leonard | Rich Gossage | 123 | 120 | 3 |
| 1978-05-14 | vs NYA | 30 | W 10-9 | 17-13 | 3 | 36,034 | Andy Hassler | Dick Tidrow | Al Hrabosky | Ken Clay | | 133 | 129 | 4 |
| 1978-05-15 | vs BOS | 31 | W 3-1 | 18-13 | 3 | 34,166 | Rich Gale | Allen Ripley | Rich Gale | Allen Ripley | | 136 | 130 | 6 |
| 1978-05-16 | vs BOS | 32 | L 2-3 | 18-14 | 3 | 23,474 | Paul Splittorff | Bill Lee | Bill Lee | Paul Splittorff | | 138 | 133 | 5 |
| 1978-05-18 | vs MIN | 33 | L 6-8 | 18-15 | 3 | 17,459 | Dennis Leonard | Geoff Zahn | Geoff Zahn | Dennis Leonard | Mike Marshall | 144 | 141 | 3 |
| 1978-05-19 | vs MIN | 34 | L 3-5 | 18-16 | 3 | 31,574 | Andy Hassler | Roger Erickson | Roger Erickson | Marty Pattin | Mike Marshall | 147 | 146 | 1 |
| 1978-05-20 | vs MIN | 35 | W 6-3 | 19-16 | 3 | 30,312 | Rich Gale | Paul Thormodsgard | Rich Gale | Paul Thormodsgard | Al Hrabosky | 153 | 149 | 4 |
| 1978-05-21 | vs MIN | 36 | L 2-3 | 19-17 | 3 | 29,079 | Paul Splittorff | Gary Serum | Gary Serum | Paul Splittorff | Mike Marshall | 155 | 152 | 3 |
| 1978-05-22 | @ SEA | 37 | L 1-10 | 19-18 | 3 | 6,190 | Dennis Leonard | Tom House | Tom House | Dennis Leonard | | 156 | 162 | -6 |
| 1978-05-23 | @ SEA | 38 | L 3-4 | 20-19 | 3 | 0 | Andy Hassler | Dick Pole | Dick Pole | Andy Hassler | Jim Todd | 159 | 166 | -7 |
| 1978-05-23 | @ SEA | 39 | W 5-3 | 20-19 | 3 | 8,275 | Larry Gura | Shane Rawley | Doug Bird | Shane Rawley | Al Hrabosky | 164 | 169 | -5 |
| 1978-05-24 | @ SEA | 40 | W 6-5 | 21-19 | 3 | 6,717 | Rich Gale | Paul Mitchell | Steve Mingori | Jim Todd | Al Hrabosky | 170 | 174 | -4 |
| 1978-05-25 | @ SEA | 41 | W 9-4 | 22-19 | 3 | 5,946 | Paul Splittorff | Glenn Abbott | Paul Splittorff | Glenn Abbott | | 179 | 178 | 1 |
| 1978-05-28 | @ MIN | 42 | W 8-7 | 23-19 | 3 | 22,266 | Andy Hassler | Paul Thormodsgard | Larry Gura | Mike Marshall | | 187 | 185 | 2 |
| 1978-05-29 | vs SEA | 43 | W 8-2 | 24-19 | 3 | 36,405 | Rich Gale | Dick Pole | Rich Gale | Dick Pole | | 195 | 187 | 8 |
| 1978-05-31 | vs SEA | 44 | W 8-3 | 25-19 | 2 | 17,071 | Paul Splittorff | Glenn Abbott | Paul Splittorff | Glenn Abbott | | 203 | 190 | 13 |
| 1978-06-01 | vs SEA | 45 | W 10-0 | 26-19 | 1 | 16,595 | Dennis Leonard | Tom House | Dennis Leonard | Tom House | | 213 | 190 | 23 |
| 1978-06-02 | vs CHA | 46 | L 1-5 | 26-20 | 1 | 23,072 | Andy Hassler | Francisco Barrios | Francisco Barrios | Andy Hassler | | 214 | 195 | 19 |
| 1978-06-03 | vs CHA | 47 | L 5-9 | 26-21 | 2 | 35,230 | Rich Gale | Ken Kravec | Ken Kravec | Rich Gale | Rich Hinton | 219 | 204 | 15 |
| 1978-06-04 | vs CHA | 48 | W 13-2 | 27-21 | 2 | 38,698 | Paul Splittorff | Wilbur Wood | Paul Splittorff | Wilbur Wood | | 232 | 206 | 26 |
| 1978-06-06 | @ TEX | 49 | L 1-2 | 27-22 | 2 | 23,880 | Dennis Leonard | Fergie Jenkins | Fergie Jenkins | Dennis Leonard | | 233 | 208 | 25 |
| 1978-06-08 | @ TEX | 50 | L 4-5 | 27-24 | 3 | 0 | Andy Hassler | Doyle Alexander | Doyle Alexander | Andy Hassler | Reggie Cleveland | 237 | 213 | 24 |
| 1978-06-08 | @ TEX | 51 | L 2-3 | 27-24 | 3 | 32,886 | Rich Gale | Jon Matlack | Steve Comer | Al Hrabosky | | 239 | 216 | 23 |
| 1978-06-09 | @ DET | 52 | L 2-3 | 27-25 | 3 | 32,309 | Paul Splittorff | Jack Billingham | Jack Billingham | Paul Splittorff | John Hiller | 241 | 219 | 22 |
| 1978-06-10 | @ DET | 53 | W 6-3 | 28-25 | 3 | 32,381 | Dennis Leonard | Bob Sykes | Dennis Leonard | Jack Morris | | 247 | 222 | 25 |
| 1978-06-11 | @ DET | 54 | L 2-5 | 28-26 | 4 | 24,210 | Larry Gura | Steve Baker | John Hiller | Al Hrabosky | | 249 | 227 | 22 |
| 1978-06-12 | vs TEX | 55 | L 5-6 | 28-27 | 4 | 38,146 | Doug Bird | Fergie Jenkins | Steve Comer | Steve Mingori | Paul Lindblad | 254 | 233 | 21 |
| 1978-06-13 | vs TEX | 56 | W 5-0 | 29-27 | 3 | 22,103 | Rich Gale | Doyle Alexander | Rich Gale | Doyle Alexander | | 259 | 233 | 26 |
| 1978-06-14 | vs DET | 57 | W 7-1 | 30-27 | 1 | 21,025 | Paul Splittorff | Jack Billingham | Paul Splittorff | Jack Billingham | | 266 | 234 | 32 |
| 1978-06-15 | vs DET | 58 | W 7-2 | 31-27 | 1 | 19,721 | Dennis Leonard | Bob Sykes | Dennis Leonard | Bob Sykes | | 273 | 236 | 37 |
| 1978-06-16 | @ CHA | 59 | W 2-1 | 32-27 | 1 | 44,785 | Larry Gura | Francisco Barrios | Larry Gura | Francisco Barrios | Al Hrabosky | 275 | 237 | 38 |
| 1978-06-17 | @ CHA | 60 | L 1-6 | 32-28 | 1 | 26,798 | Rich Gale | Ken Kravec | Ken Kravec | Rich Gale | Jim Willoughby | 276 | 243 | 33 |
| 1978-06-18 | @ CHA | 61 | W 3-2 | 33-29 | 1 | 0 | Andy Hassler | Wilbur Wood | Al Hrabosky | Lerrin LaGrow | | 279 | 245 | 34 |
| 1978-06-18 | @ CHA | 62 | L 0-11 | 33-29 | 1 | 40,598 | Paul Splittorff | Ron Schueler | Ron Schueler | Paul Splittorff | Jim Willoughby | 279 | 256 | 23 |
| 1978-06-19 | vs CLE | 63 | W 6-5 | 34-29 | 1 | 25,660 | Dennis Leonard | David Clyde | Dennis Leonard | David Clyde | Al Hrabosky | 285 | 261 | 24 |
| 1978-06-20 | vs CLE | 64 | W 3-2 | 35-29 | 1 | 20,444 | Larry Gura | Rick Wise | Larry Gura | Rick Wise | | 288 | 263 | 25 |
| 1978-06-21 | vs CLE | 65 | L 2-4 | 35-30 | 1 | 23,818 | Rich Gale | Don Hood | Dan Spillner | Doug Bird | Jim Kern | 290 | 267 | 23 |
| 1978-06-23 | vs OAK | 66 | W 5-3 | 36-31 | 1 | 0 | Paul Splittorff | Rick Langford | Paul Splittorff | Rick Langford | Al Hrabosky | 295 | 270 | 25 |
| 1978-06-23 | vs OAK | 67 | L 4-5 | 36-31 | 1 | 38,841 | Dennis Leonard | Tim Conroy | Pete Broberg | Dennis Leonard | Dave Heaverlo | 299 | 275 | 24 |
| 1978-06-24 | vs OAK | 68 | W 7-5 | 37-31 | 1 | 35,423 | Andy Hassler | Steve Renko | Andy Hassler | Steve Renko | Al Hrabosky | 306 | 280 | 26 |
| 1978-06-25 | vs OAK | 69 | L 3-6 | 37-32 | 2 | 32,842 | Larry Gura | Matt Keough | Bob Lacey | Larry Gura | Elias Sosa | 309 | 286 | 23 |
| 1978-06-26 | @ CAL | 70 | W 4-0 | 38-32 | 1 | 29,829 | Rich Gale | Frank Tanana | Rich Gale | Frank Tanana | | 313 | 286 | 27 |
| 1978-06-27 | @ CAL | 71 | L 4-5 | 38-33 | 2 | 21,459 | Dennis Leonard | Ken Brett | Tom Griffin | Steve Mingori | Dave LaRoche | 317 | 291 | 26 |
| 1978-06-28 | @ CAL | 72 | L 5-9 | 38-34 | 2 | 22,742 | Paul Splittorff | Chris Knapp | Chris Knapp | Paul Splittorff | Paul Hartzell | 322 | 300 | 22 |
| 1978-06-29 | @ CAL | 73 | L 1-3 | 38-35 | 2 | 17,038 | Marty Pattin | Dave Frost | Dave Frost | Al Hrabosky | Dave LaRoche | 323 | 303 | 20 |
| 1978-06-30 | @ OAK | 74 | L 1-2 | 38-36 | 3 | 16,506 | Rich Gale | Matt Keough | Matt Keough | Rich Gale | | 324 | 305 | 19 |
| 1978-07-01 | @ OAK | 75 | L 2-4 | 38-37 | 3 | 5,062 | Dennis Leonard | John Henry Johnson | John Henry Johnson | Dennis Leonard | | 326 | 309 | 17 |
| 1978-07-02 | @ OAK | 76 | W 4-2 | 39-38 | 3 | 0 | Larry Gura | Rick Langford | Larry Gura | Bob Lacey | Al Hrabosky | 330 | 311 | 19 |
| 1978-07-02 | @ OAK | 77 | L 3-9 | 39-38 | 3 | 13,486 | Andy Hassler | Steve Renko | Steve Renko | Andy Hassler | | 333 | 320 | 13 |
| 1978-07-03 | vs CAL | 78 | L 4-7 | 39-39 | 4 | 39,928 | Doug Bird | Chris Knapp | Chris Knapp | Doug Bird | Dave LaRoche | 337 | 327 | 10 |
| 1978-07-04 | vs CAL | 79 | W 4-3 | 40-39 | 4 | 40,030 | Rich Gale | Dave Frost | Rich Gale | Paul Hartzell | | 341 | 330 | 11 |
| 1978-07-05 | vs CAL | 80 | W 10-1 | 41-39 | 4 | 20,347 | Dennis Leonard | Nolan Ryan | Dennis Leonard | Nolan Ryan | | 351 | 331 | 20 |
| 1978-07-06 | vs CAL | 81 | L 2-9 | 41-40 | 4 | 19,783 | Marty Pattin | Don Aase | Don Aase | Marty Pattin | | 353 | 340 | 13 |
| 1978-07-07 | vs BAL | 82 | W 3-1 | 42-40 | 2 | 23,314 | Paul Splittorff | Scott McGregor | Paul Splittorff | Scott McGregor | | 356 | 341 | 15 |
| 1978-07-08 | vs BAL | 83 | W 11-3 | 43-40 | 2 | 34,587 | Rich Gale | Dennis Martinez | Rich Gale | Dennis Martinez | | 367 | 344 | 23 |
| 1978-07-09 | vs BAL | 84 | W 10-4 | 44-40 | 2 | 24,662 | Dennis Leonard | Mike Flanagan | Dennis Leonard | Mike Flanagan | | 377 | 348 | 29 |
| 1978-07-13 | @ MIL | 85 | L 2-13 | 44-41 | 2 | 16,706 | Paul Splittorff | Mike Caldwell | Mike Caldwell | Paul Splittorff | | 379 | 361 | 18 |
| 1978-07-14 | @ MIL | 86 | W 9-2 | 45-41 | 2 | 43,993 | Rich Gale | Andy Replogle | Rich Gale | Andy Replogle | | 388 | 363 | 25 |
| 1978-07-15 | @ NYA | 87 | W 8-2 | 46-41 | 2 | 34,979 | Dennis Leonard | Ed Figueroa | Dennis Leonard | Ed Figueroa | | 396 | 365 | 31 |
| 1978-07-16 | @ NYA | 88 | W 3-1 | 47-41 | 2 | 45,089 | Larry Gura | Jim Beattie | Larry Gura | Jim Beattie | Al Hrabosky | 399 | 366 | 33 |
| 1978-07-17 | @ NYA | 89 | W 9-7 | 48-41 | 1 | 27,020 | Paul Splittorff | Catfish Hunter | Al Hrabosky | Rich Gossage | | 408 | 373 | 35 |
| 1978-07-19 | vs TEX | 90 | W 11-4 | 49-41 | 1 | 28,420 | Rich Gale | Fergie Jenkins | Rich Gale | Fergie Jenkins | | 419 | 377 | 42 |
| 1978-07-20 | vs TEX | 91 | W 2-1 | 50-41 | 1 | 26,620 | Dennis Leonard | Doyle Alexander | Dennis Leonard | Doyle Alexander | | 421 | 378 | 43 |
| 1978-07-21 | vs BOS | 92 | W 9-0 | 51-41 | 1 | 39,841 | Paul Splittorff | Dennis Eckersley | Paul Splittorff | Dennis Eckersley | | 430 | 378 | 52 |
| 1978-07-22 | vs BOS | 93 | W 6-5 | 52-41 | 1 | 37,538 | Doug Bird | Luis Tiant | Al Hrabosky | Dick Drago | | 436 | 383 | 53 |
| 1978-07-23 | vs BOS | 94 | W 7-3 | 53-41 | 1 | 39,425 | Rich Gale | Jim Wright | Marty Pattin | Jim Wright | | 443 | 386 | 57 |
| 1978-07-24 | vs NYA | 95 | W 5-2 | 54-41 | 1 | 38,859 | Dennis Leonard | Dick Tidrow | Dennis Leonard | Dick Tidrow | | 448 | 388 | 60 |
| 1978-07-25 | vs NYA | 96 | L 0-4 | 54-42 | 1 | 40,183 | Paul Splittorff | Ron Guidry | Ron Guidry | Paul Splittorff | | 448 | 392 | 56 |
| 1978-07-26 | vs SEA | 97 | W 12-3 | 55-42 | 1 | 20,327 | Doug Bird | Mike Parrott | Doug Bird | Mike Parrott | Steve Mingori | 460 | 395 | 65 |
| 1978-07-27 | vs SEA | 98 | W 3-1 | 56-42 | 1 | 26,712 | Larry Gura | Paul Mitchell | Larry Gura | Paul Mitchell | | 463 | 396 | 67 |
| 1978-07-28 | @ BOS | 99 | W 4-0 | 57-42 | 1 | 35,348 | Rich Gale | Mike Torrez | Rich Gale | Mike Torrez | | 467 | 396 | 71 |
| 1978-07-29 | @ BOS | 100 | L 0-1 | 57-43 | 1 | 35,098 | Dennis Leonard | Jim Wright | Jim Wright | Dennis Leonard | | 467 | 397 | 70 |
| 1978-07-30 | @ BOS | 101 | W 2-1 | 58-43 | 1 | 34,626 | Paul Splittorff | Bill Lee | Paul Splittorff | Bill Lee | Al Hrabosky | 469 | 398 | 71 |
| 1978-07-31 | @ CLE | 102 | L 3-4 | 58-44 | 1 | 8,149 | Larry Gura | Rick Waits | Sid Monge | Al Hrabosky | | 472 | 402 | 70 |
| 1978-08-01 | @ CLE | 103 | L 1-2 | 58-45 | 1 | 8,236 | Rich Gale | David Clyde | Jim Kern | Steve Mingori | | 473 | 404 | 69 |
| 1978-08-02 | @ CLE | 104 | L 2-5 | 58-46 | 1 | 7,834 | Dennis Leonard | Dave Freisleben | Paul Reuschel | Dennis Leonard | | 475 | 409 | 66 |
| 1978-08-04 | vs TOR | 105 | L 4-5 | 58-47 | 1 | 35,064 | Paul Splittorff | Jesse Jefferson | Victor Cruz | Al Hrabosky | | 479 | 414 | 65 |
| 1978-08-05 | vs TOR | 106 | W 5-3 | 59-47 | 1 | 34,179 | Larry Gura | Dave Lemanczyk | Larry Gura | Dave Lemanczyk | Steve Mingori | 484 | 417 | 67 |
| 1978-08-06 | vs TOR | 107 | W 12-5 | 60-47 | 1 | 35,404 | Rich Gale | Balor Moore | Rich Gale | Balor Moore | | 496 | 422 | 74 |
| 1978-08-07 | vs CHA | 108 | L 3-5 | 60-48 | 1 | 39,847 | Dennis Leonard | Francisco Barrios | Lerrin LaGrow | Dennis Leonard | | 499 | 427 | 72 |
| 1978-08-08 | vs CHA | 109 | W 10-4 | 61-48 | 1 | 29,976 | Paul Splittorff | Mike Proly | Paul Splittorff | Mike Proly | Marty Pattin | 509 | 431 | 78 |
| 1978-08-09 | @ BAL | 110 | W 2-0 | 62-48 | 1 | 12,859 | Larry Gura | Scott McGregor | Larry Gura | Scott McGregor | | 511 | 431 | 80 |
| 1978-08-10 | @ BAL | 111 | L 2-3 | 62-49 | 1 | 9,221 | Doug Bird | Jim Palmer | Jim Palmer | Doug Bird | Don Stanhouse | 513 | 434 | 79 |
| 1978-08-11 | @ TOR | 112 | W 9-8 | 63-49 | 1 | 20,602 | Dennis Leonard | Balor Moore | Al Hrabosky | Victor Cruz | | 522 | 442 | 80 |
| 1978-08-12 | @ TOR | 113 | L 2-5 | 63-50 | 1 | 23,132 | Paul Splittorff | Jim Clancy | Jim Clancy | Paul Splittorff | | 524 | 447 | 77 |
| 1978-08-13 | @ TOR | 114 | L 2-3 | 63-51 | 1 | 30,270 | Larry Gura | Tom Underwood | Mike Willis | Al Hrabosky | | 526 | 450 | 76 |
| 1978-08-14 | @ DET | 115 | L 2-11 | 63-52 | 1 | 31,409 | Rich Gale | Milt Wilcox | Milt Wilcox | Rich Gale | | 528 | 461 | 67 |
| 1978-08-15 | @ DET | 116 | W 4-2 | 64-52 | 1 | 33,365 | Dennis Leonard | Kip Young | Dennis Leonard | Kip Young | Al Hrabosky | 532 | 463 | 69 |
| 1978-08-16 | @ MIN | 117 | L 1-5 | 65-53 | 1 | 0 | Doug Bird | Geoff Zahn | Geoff Zahn | Doug Bird | | 533 | 468 | 65 |
| 1978-08-16 | @ MIN | 118 | W 11-7 | 65-53 | 1 | 14,640 | Paul Splittorff | Stan Perzanowski | Paul Splittorff | Stan Perzanowski | Steve Mingori | 544 | 475 | 69 |
| 1978-08-17 | @ MIN | 119 | L 5-6 | 65-54 | 1 | 15,936 | Larry Gura | Roger Erickson | Roger Erickson | Larry Gura | | 549 | 481 | 68 |
| 1978-08-18 | vs TEX | 120 | L 3-4 | 65-55 | 1 | 40,112 | Rich Gale | Doc Medich | Doc Medich | Rich Gale | | 552 | 485 | 67 |
| 1978-08-19 | vs TEX | 121 | W 3-0 | 66-55 | 1 | 37,604 | Dennis Leonard | Fergie Jenkins | Dennis Leonard | Fergie Jenkins | | 555 | 485 | 70 |
| 1978-08-20 | vs TEX | 122 | W 2-1 | 67-55 | 1 | 38,423 | Paul Splittorff | Jon Matlack | Paul Splittorff | Jon Matlack | | 557 | 486 | 71 |
| 1978-08-22 | @ CHA | 123 | W 6-3 | 68-55 | 1 | 21,689 | Larry Gura | Ross Baumgarten | Larry Gura | Ross Baumgarten | Al Hrabosky | 563 | 489 | 74 |
| 1978-08-23 | @ CHA | 124 | L 0-3 | 68-56 | 1 | 15,550 | Dennis Leonard | Ken Kravec | Ken Kravec | Dennis Leonard | | 563 | 492 | 71 |
| 1978-08-24 | @ CHA | 125 | L 1-4 | 68-57 | 2 | 14,524 | Paul Splittorff | Mike Proly | Mike Proly | Paul Splittorff | Lerrin LaGrow | 564 | 496 | 68 |
| 1978-08-25 | @ TEX | 126 | L 2-7 | 68-58 | 2 | 36,750 | Rich Gale | Jon Matlack | Jon Matlack | Rich Gale | | 566 | 503 | 63 |
| 1978-08-26 | @ TEX | 127 | L 4-8 | 68-59 | 2 | 33,084 | Larry Gura | Dock Ellis | Dock Ellis | Larry Gura | Len Barker | 570 | 511 | 59 |
| 1978-08-27 | @ TEX | 128 | W 4-2 | 69-59 | 1 | 25,242 | Dennis Leonard | Doc Medich | Dennis Leonard | Doc Medich | Al Hrabosky | 574 | 513 | 61 |
| 1978-08-28 | vs CHA | 129 | W 3-2 | 70-59 | 1 | 27,562 | Paul Splittorff | Ken Kravec | Al Hrabosky | Ken Kravec | | 577 | 515 | 62 |
| 1978-08-29 | vs CHA | 130 | L 3-9 | 70-60 | 1 | 19,343 | Rich Gale | Mike Proly | Mike Proly | Rich Gale | Lerrin LaGrow | 580 | 524 | 56 |
| 1978-08-30 | vs CHA | 131 | W 12-0 | 71-60 | 1 | 19,053 | Larry Gura | Francisco Barrios | Larry Gura | Francisco Barrios | | 592 | 524 | 68 |
| 1978-09-01 | vs DET | 132 | L 2-6 | 71-61 | 1 | 32,329 | Dennis Leonard | Jack Billingham | Jack Billingham | Dennis Leonard | | 594 | 530 | 64 |
| 1978-09-02 | vs DET | 133 | W 8-3 | 72-61 | 1 | 34,004 | Paul Splittorff | Jim Slaton | Paul Splittorff | Jim Slaton | | 602 | 533 | 69 |
| 1978-09-03 | vs DET | 134 | W 6-2 | 73-61 | 1 | 27,217 | Larry Gura | Dave Rozema | Larry Gura | Dave Rozema | | 608 | 535 | 73 |
| 1978-09-04 | @ OAK | 135 | W 5-3 | 74-61 | 1 | 7,550 | Rich Gale | Mike Norris | Rich Gale | Mike Norris | Al Hrabosky | 613 | 538 | 75 |
| 1978-09-05 | @ OAK | 136 | W 3-0 | 75-61 | 1 | 1,376 | Dennis Leonard | Steve Renko | Dennis Leonard | Steve Renko | | 616 | 538 | 78 |
| 1978-09-06 | @ OAK | 137 | W 11-8 | 76-61 | 1 | 1,350 | Paul Splittorff | Matt Keough | Al Hrabosky | Dave Heaverlo | Marty Pattin | 627 | 546 | 81 |
| 1978-09-08 | @ CAL | 138 | W 9-7 | 77-61 | 1 | 26,507 | Larry Gura | Chris Knapp | Doug Bird | Dave LaRoche | | 636 | 553 | 83 |
| 1978-09-09 | @ CAL | 139 | L 2-3 | 77-63 | 1 | 0 | Rich Gale | Don Aase | Don Aase | Rich Gale | Dave LaRoche | 638 | 556 | 82 |
| 1978-09-09 | @ CAL | 140 | L 2-4 | 77-63 | 1 | 41,511 | Dennis Leonard | Dave Frost | Dave Frost | Dennis Leonard | | 640 | 560 | 80 |
| 1978-09-10 | @ CAL | 141 | L 3-13 | 77-64 | 1 | 24,793 | Paul Splittorff | Nolan Ryan | Nolan Ryan | Paul Splittorff | | 643 | 573 | 70 |
| 1978-09-11 | vs OAK | 142 | W 7-2 | 78-64 | 1 | 24,765 | Marty Pattin | Matt Keough | Marty Pattin | Matt Keough | | 650 | 575 | 75 |
| 1978-09-12 | vs OAK | 143 | W 8-1 | 79-64 | 1 | 21,379 | Larry Gura | Rick Langford | Larry Gura | Rick Langford | | 658 | 576 | 82 |
| 1978-09-13 | vs OAK | 144 | W 9-1 | 80-64 | 1 | 18,359 | Dennis Leonard | John Henry Johnson | Dennis Leonard | John Henry Johnson | | 667 | 577 | 90 |
| 1978-09-14 | vs OAK | 145 | W 5-1 | 81-64 | 1 | 19,617 | Paul Splittorff | Steve Renko | Paul Splittorff | Steve Renko | | 672 | 578 | 94 |
| 1978-09-15 | vs CAL | 146 | W 3-2 | 82-64 | 1 | 30,847 | Rich Gale | Nolan Ryan | Al Hrabosky | Nolan Ryan | | 675 | 580 | 95 |
| 1978-09-16 | vs CAL | 147 | L 3-4 | 82-65 | 1 | 40,237 | Marty Pattin | Paul Hartzell | Dyar Miller | Al Hrabosky | Dave LaRoche | 678 | 584 | 94 |
| 1978-09-17 | vs CAL | 148 | W 5-0 | 83-65 | 1 | 37,590 | Dennis Leonard | Frank Tanana | Dennis Leonard | Frank Tanana | | 683 | 584 | 99 |
| 1978-09-18 | @ SEA | 149 | W 7-6 | 84-65 | 1 | 5,766 | Larry Gura | Paul Mitchell | Doug Bird | Mike Parrott | Al Hrabosky | 690 | 590 | 100 |
| 1978-09-19 | @ SEA | 150 | W 9-8 | 85-65 | 1 | 5,946 | Paul Splittorff | Rick Honeycutt | Paul Splittorff | Rick Honeycutt | | 699 | 598 | 101 |
| 1978-09-20 | vs MIL | 151 | L 4-5 | 85-66 | 1 | 15,917 | Rich Gale | Lary Sorensen | Jerry Augustine | Bill Paschall | | 703 | 603 | 100 |
| 1978-09-21 | vs MIL | 152 | W 8-4 | 86-66 | 1 | 17,799 | Dennis Leonard | Andy Replogle | Dennis Leonard | Andy Replogle | | 711 | 607 | 104 |
| 1978-09-22 | @ MIN | 153 | W 4-2 | 87-67 | 1 | 0 | Larry Gura | Darrell Jackson | Larry Gura | Darrell Jackson | | 715 | 609 | 106 |
| 1978-09-22 | @ MIN | 154 | L 0-4 | 87-67 | 1 | 5,175 | Marty Pattin | Geoff Zahn | Geoff Zahn | Marty Pattin | | 715 | 613 | 102 |
| 1978-09-23 | @ MIN | 155 | W 3-1 | 88-67 | 1 | 13,288 | Paul Splittorff | Roger Erickson | Paul Splittorff | Roger Erickson | Al Hrabosky | 718 | 614 | 104 |
| 1978-09-24 | @ MIN | 156 | L 4-6 | 88-68 | 1 | 6,627 | Rich Gale | Dave Goltz | Dave Goltz | Steve Mingori | | 722 | 620 | 102 |
| 1978-09-25 | vs SEA | 157 | W 7-2 | 89-68 | 1 | 21,890 | Dennis Leonard | Rick Honeycutt | Dennis Leonard | Rick Honeycutt | | 729 | 622 | 107 |
| 1978-09-26 | vs SEA | 158 | W 4-1 | 90-68 | 1 | 22,415 | Larry Gura | Glenn Abbott | Larry Gura | Glenn Abbott | | 733 | 623 | 110 |
| 1978-09-27 | vs SEA | 159 | L 2-4 | 90-69 | 1 | 14,737 | Paul Splittorff | Byron McLaughlin | Byron McLaughlin | Paul Splittorff | | 735 | 627 | 108 |
| 1978-09-29 | vs MIN | 160 | W 4-0 | 91-69 | 1 | 31,794 | Dennis Leonard | Darrell Jackson | Dennis Leonard | Darrell Jackson | | 739 | 627 | 112 |
| 1978-09-30 | vs MIN | 161 | L 3-7 | 91-70 | 1 | 29,089 | Steve Busby | Gary Serum | Mike Marshall | Randy McGilberry | | 742 | 634 | 108 |
| 1978-10-01 | vs MIN | 162 | W 1-0 | 92-70 | 1 | 23,794 | Larry Gura | Geoff Zahn | George Throop | Geoff Zahn | Bill Paschall | 743 | 634 | 109 |