| 1978-04-08 | vs NYA | 1 | W 2-1 | 1-0 | 2 | 40,078 | Jon Matlack | Ron Guidry | Jon Matlack | Rich Gossage | | 2 | 1 | 1 |
| 1978-04-09 | vs NYA | 2 | L 1-7 | 1-1 | 5 | 20,243 | Doyle Alexander | Ed Figueroa | Ed Figueroa | Doyle Alexander | | 3 | 8 | -5 |
| 1978-04-10 | vs NYA | 3 | W 5-2 | 2-1 | 4 | 14,299 | Dock Ellis | Dick Tidrow | Dock Ellis | Dick Tidrow | Roger Moret | 8 | 10 | -2 |
| 1978-04-11 | vs DET | 4 | L 2-6 | 2-2 | 6 | 13,764 | Doc Medich | Dave Rozema | Dave Rozema | Doc Medich | | 10 | 16 | -6 |
| 1978-04-12 | vs DET | 5 | L 2-3 | 2-3 | 6 | 26,049 | Jon Matlack | Mark Fidrych | Mark Fidrych | Jon Matlack | | 12 | 19 | -7 |
| 1978-04-14 | @ BOS | 6 | L 4-5 | 2-4 | 6 | 34,747 | Doyle Alexander | Dennis Eckersley | Dick Drago | Len Barker | | 16 | 24 | -8 |
| 1978-04-15 | @ BOS | 7 | L 4-12 | 2-5 | 6 | 18,624 | Dock Ellis | Bill Lee | Bill Lee | Dock Ellis | | 20 | 36 | -16 |
| 1978-04-16 | @ BOS | 8 | L 6-8 | 2-6 | 7 | 22,168 | Doc Medich | Allen Ripley | Bob Stanley | Jim Umbarger | Tom Burgmeier | 26 | 44 | -18 |
| 1978-04-17 | @ CLE | 9 | L 0-6 | 2-7 | 7 | 3,713 | Jon Matlack | Rick Waits | Rick Waits | Jon Matlack | | 26 | 50 | -24 |
| 1978-04-22 | @ DET | 10 | L 6-7 | 2-8 | 7 | 22,054 | Doyle Alexander | Jack Morris | John Hiller | Fergie Jenkins | | 32 | 57 | -25 |
| 1978-04-23 | @ DET | 11 | L 6-9 | 3-9 | 7 | 0 | Jon Matlack | Jim Slaton | Jim Slaton | Jon Matlack | Steve Foucault | 38 | 66 | -28 |
| 1978-04-23 | @ DET | 12 | W 2-1 | 3-9 | 7 | 20,615 | Jim Umbarger | Dave Rozema | Len Barker | Jim Crawford | | 40 | 67 | -27 |
| 1978-04-24 | vs KCA | 13 | L 6-8 | 3-10 | 7 | 15,530 | Dock Ellis | Jim Colborn | Doug Bird | Reggie Cleveland | | 46 | 75 | -29 |
| 1978-04-25 | vs KCA | 14 | W 4-1 | 4-10 | 7 | 14,154 | Fergie Jenkins | Dennis Leonard | Fergie Jenkins | Dennis Leonard | | 50 | 76 | -26 |
| 1978-04-26 | vs CLE | 15 | W 3-0 | 5-10 | 5 | 9,915 | Doyle Alexander | Rick Wise | Doyle Alexander | Rick Wise | | 53 | 76 | -23 |
| 1978-04-27 | vs CLE | 16 | W 3-1 | 6-10 | 5 | 11,133 | Jon Matlack | Rick Waits | Jon Matlack | Rick Waits | Len Barker | 56 | 77 | -21 |
| 1978-04-28 | vs BOS | 17 | W 5-4 | 7-10 | 4 | 29,731 | Jim Umbarger | Luis Tiant | Reggie Cleveland | Bill Campbell | | 61 | 81 | -20 |
| 1978-04-29 | vs BOS | 18 | W 4-1 | 8-10 | 4 | 34,101 | Dock Ellis | Dennis Eckersley | Dock Ellis | Dennis Eckersley | | 65 | 82 | -17 |
| 1978-04-30 | vs BOS | 19 | W 2-1 | 9-10 | 4 | 22,554 | Fergie Jenkins | Bill Lee | Fergie Jenkins | Bill Campbell | | 67 | 83 | -16 |
| 1978-05-03 | @ BAL | 20 | W 2-1 | 10-10 | 4 | 6,118 | Doyle Alexander | Jim Palmer | Doyle Alexander | Don Stanhouse | | 69 | 84 | -15 |
| 1978-05-05 | @ NYA | 21 | L 2-5 | 10-11 | 4 | 17,285 | Jon Matlack | Ron Guidry | Ron Guidry | Jon Matlack | Rich Gossage | 71 | 89 | -18 |
| 1978-05-06 | @ NYA | 22 | W 9-5 | 11-11 | 4 | 19,788 | Jim Umbarger | Dick Tidrow | Jim Umbarger | Dick Tidrow | | 80 | 94 | -14 |
| 1978-05-07 | @ NYA | 23 | L 2-3 | 11-12 | 4 | 53,829 | Dock Ellis | Jim Beattie | Rich Gossage | Len Barker | | 82 | 97 | -15 |
| 1978-05-09 | @ MIL | 24 | W 7-1 | 12-12 | 4 | 4,790 | Fergie Jenkins | Mike Caldwell | Fergie Jenkins | Mike Caldwell | | 89 | 98 | -9 |
| 1978-05-10 | @ MIL | 25 | W 4-3 | 13-12 | 4 | 6,528 | Doyle Alexander | Lary Sorensen | Doyle Alexander | Lary Sorensen | Reggie Cleveland | 93 | 101 | -8 |
| 1978-05-12 | vs BAL | 26 | W 9-3 | 14-12 | 4 | 30,803 | Jon Matlack | Jim Palmer | Jon Matlack | Jim Palmer | | 102 | 104 | -2 |
| 1978-05-13 | vs BAL | 27 | L 1-5 | 14-13 | 4 | 32,700 | Jim Umbarger | Scott McGregor | Scott McGregor | Jim Umbarger | | 103 | 109 | -6 |
| 1978-05-14 | vs BAL | 28 | L 2-3 | 14-14 | 4 | 16,440 | Dock Ellis | Mike Flanagan | John Flinn | Dock Ellis | Don Stanhouse | 105 | 112 | -7 |
| 1978-05-15 | vs MIL | 29 | W 8-6 | 15-14 | 4 | 11,622 | Fergie Jenkins | Bill Travers | Fergie Jenkins | Bill Travers | Reggie Cleveland | 113 | 118 | -5 |
| 1978-05-16 | vs MIL | 30 | L 3-4 | 15-15 | 4 | 11,351 | Doyle Alexander | Lary Sorensen | Lary Sorensen | Doyle Alexander | | 116 | 122 | -6 |
| 1978-05-17 | vs OAK | 31 | W 4-3 | 16-15 | 4 | 15,635 | Jon Matlack | John Henry Johnson | Jon Matlack | John Henry Johnson | | 120 | 125 | -5 |
| 1978-05-18 | vs OAK | 32 | W 6-4 | 17-15 | 4 | 21,257 | Jim Umbarger | Matt Keough | Jim Umbarger | Matt Keough | Reggie Cleveland | 126 | 129 | -3 |
| 1978-05-19 | @ SEA | 33 | L 5-6 | 18-16 | 4 | 0 | Dock Ellis | Dick Pole | Tom House | Steve Comer | | 131 | 135 | -4 |
| 1978-05-19 | @ SEA | 34 | W 4-2 | 18-16 | 4 | 8,933 | Doc Medich | Paul Mitchell | Doc Medich | Paul Mitchell | Paul Lindblad | 135 | 137 | -2 |
| 1978-05-20 | @ SEA | 35 | L 3-7 | 18-17 | 4 | 34,835 | Fergie Jenkins | Glenn Abbott | Shane Rawley | Fergie Jenkins | Enrique Romo | 138 | 144 | -6 |
| 1978-05-21 | @ SEA | 36 | W 5-4 | 19-17 | 4 | 28,689 | Doyle Alexander | Byron McLaughlin | Doyle Alexander | Enrique Romo | Reggie Cleveland | 143 | 148 | -5 |
| 1978-05-22 | @ MIN | 37 | L 0-2 | 19-18 | 4 | 6,108 | Jon Matlack | Geoff Zahn | Geoff Zahn | Jon Matlack | Mike Marshall | 143 | 150 | -7 |
| 1978-05-23 | @ MIN | 38 | L 2-5 | 19-19 | 4 | 6,791 | Jim Umbarger | Roger Erickson | Roger Erickson | Jim Umbarger | | 145 | 155 | -10 |
| 1978-05-24 | @ MIN | 39 | W 3-2 | 20-19 | 4 | 7,598 | Dock Ellis | Paul Thormodsgard | Paul Lindblad | Mike Marshall | Doc Medich | 148 | 157 | -9 |
| 1978-05-25 | @ MIN | 40 | W 7-1 | 21-19 | 4 | 7,644 | Fergie Jenkins | Gary Serum | Fergie Jenkins | Gary Serum | | 155 | 158 | -3 |
| 1978-05-26 | vs SEA | 41 | L 4-6 | 21-20 | 4 | 17,490 | Doyle Alexander | Byron McLaughlin | Shane Rawley | Doyle Alexander | Enrique Romo | 159 | 164 | -5 |
| 1978-05-27 | vs SEA | 42 | W 3-2 | 22-20 | 4 | 23,019 | Jon Matlack | Tom House | Jon Matlack | Tom House | Reggie Cleveland | 162 | 166 | -4 |
| 1978-05-29 | vs MIN | 43 | W 7-1 | 23-21 | 4 | 0 | Dock Ellis | Gary Serum | Dock Ellis | Gary Serum | | 169 | 167 | 2 |
| 1978-05-29 | vs MIN | 44 | L 2-7 | 23-21 | 4 | 28,317 | Jim Umbarger | Roger Erickson | Roger Erickson | Jim Umbarger | Mike Marshall | 171 | 174 | -3 |
| 1978-05-30 | vs MIN | 45 | L 0-2 | 23-22 | 4 | 12,718 | Fergie Jenkins | Geoff Zahn | Geoff Zahn | Fergie Jenkins | Mike Marshall | 171 | 176 | -5 |
| 1978-06-01 | vs MIN | 46 | W 10-7 | 24-22 | 4 | 16,084 | Doyle Alexander | Paul Thormodsgard | Steve Comer | Mike Marshall | | 181 | 183 | -2 |
| 1978-06-02 | @ TOR | 47 | L 1-3 | 24-23 | 4 | 25,273 | Jon Matlack | Jesse Jefferson | Jesse Jefferson | Jon Matlack | | 182 | 186 | -4 |
| 1978-06-03 | @ TOR | 48 | L 3-4 | 24-24 | 4 | 32,021 | Jim Umbarger | Tom Underwood | Tom Underwood | Jim Umbarger | Tom Murphy | 185 | 190 | -5 |
| 1978-06-04 | @ TOR | 49 | W 9-5 | 25-24 | 4 | 28,374 | Dock Ellis | Dave Lemanczyk | Dock Ellis | Dave Lemanczyk | Steve Comer | 194 | 195 | -1 |
| 1978-06-06 | vs KCA | 50 | W 2-1 | 26-24 | 3 | 23,880 | Fergie Jenkins | Dennis Leonard | Fergie Jenkins | Dennis Leonard | | 196 | 196 | 0 |
| 1978-06-08 | vs KCA | 51 | W 5-4 | 28-24 | 2 | 0 | Doyle Alexander | Andy Hassler | Doyle Alexander | Andy Hassler | Reggie Cleveland | 201 | 200 | 1 |
| 1978-06-08 | vs KCA | 52 | W 3-2 | 28-24 | 2 | 32,886 | Jon Matlack | Rich Gale | Steve Comer | Al Hrabosky | | 204 | 202 | 2 |
| 1978-06-09 | vs CHA | 53 | L 3-4 | 28-25 | 2 | 17,511 | Doc Medich | Pablo Torrealba | Ron Schueler | Doc Medich | Lerrin LaGrow | 207 | 206 | 1 |
| 1978-06-10 | vs CHA | 54 | W 4-3 | 29-25 | 2 | 27,735 | Dock Ellis | Steve Stone | Dock Ellis | Steve Stone | | 211 | 209 | 2 |
| 1978-06-11 | vs CHA | 55 | L 1-2 | 29-26 | 2 | 22,861 | Roger Moret | Francisco Barrios | Francisco Barrios | Reggie Cleveland | Lerrin LaGrow | 212 | 211 | 1 |
| 1978-06-12 | @ KCA | 56 | W 6-5 | 30-26 | 2 | 38,146 | Fergie Jenkins | Doug Bird | Steve Comer | Steve Mingori | Paul Lindblad | 218 | 216 | 2 |
| 1978-06-13 | @ KCA | 57 | L 0-5 | 30-27 | 2 | 22,103 | Doyle Alexander | Rich Gale | Rich Gale | Doyle Alexander | | 218 | 221 | -3 |
| 1978-06-14 | @ CHA | 58 | L 1-4 | 30-28 | 3 | 22,489 | Jon Matlack | Ron Schueler | Ron Schueler | Jon Matlack | Jim Willoughby | 219 | 225 | -6 |
| 1978-06-15 | @ CHA | 59 | L 1-3 | 30-29 | 3 | 27,740 | Doc Medich | Steve Stone | Steve Stone | Doc Medich | Lerrin LaGrow | 220 | 228 | -8 |
| 1978-06-16 | vs TOR | 60 | L 3-8 | 30-31 | 4 | 0 | Dock Ellis | Tom Underwood | Tom Underwood | Dock Ellis | | 223 | 236 | -13 |
| 1978-06-16 | vs TOR | 61 | L 2-5 | 30-31 | 4 | 20,660 | Roger Moret | Jesse Jefferson | Jesse Jefferson | Roger Moret | Tom Murphy | 225 | 241 | -16 |
| 1978-06-17 | vs TOR | 62 | W 13-2 | 31-31 | 4 | 30,033 | Fergie Jenkins | Jim Clancy | Fergie Jenkins | Jim Clancy | | 238 | 243 | -5 |
| 1978-06-18 | vs TOR | 63 | W 3-2 | 32-31 | 3 | 24,645 | Doyle Alexander | Balor Moore | Reggie Cleveland | Tom Murphy | | 241 | 245 | -4 |
| 1978-06-19 | vs OAK | 64 | L 1-2 | 32-32 | 4 | 17,029 | Jon Matlack | Steve Renko | Steve Renko | Jon Matlack | Elias Sosa | 242 | 247 | -5 |
| 1978-06-20 | vs OAK | 65 | W 5-4 | 33-32 | 3 | 17,394 | Doc Medich | Matt Keough | Jim Umbarger | Dave Heaverlo | | 247 | 251 | -4 |
| 1978-06-22 | vs OAK | 66 | W 8-2 | 34-32 | 3 | 20,599 | Dock Ellis | Mike Morgan | Dock Ellis | Mike Morgan | | 255 | 253 | 2 |
| 1978-06-23 | vs CAL | 67 | W 7-0 | 36-32 | 2 | 0 | Fergie Jenkins | Chris Knapp | Fergie Jenkins | Chris Knapp | | 262 | 253 | 9 |
| 1978-06-23 | vs CAL | 68 | W 8-4 | 36-32 | 2 | 27,816 | Doyle Alexander | Tom Griffin | Doyle Alexander | Tom Griffin | Reggie Cleveland | 270 | 257 | 13 |
| 1978-06-24 | vs CAL | 69 | W 3-0 | 37-32 | 2 | 30,574 | Jon Matlack | Dave Frost | Jon Matlack | Dave Frost | | 273 | 257 | 16 |
| 1978-06-25 | vs CAL | 70 | W 7-0 | 38-32 | 1 | 22,821 | Doc Medich | Don Aase | Doc Medich | Don Aase | | 280 | 257 | 23 |
| 1978-06-27 | @ OAK | 71 | W 3-1 | 39-32 | 1 | 3,619 | Dock Ellis | Rick Langford | Dock Ellis | Rick Langford | Reggie Cleveland | 283 | 258 | 25 |
| 1978-06-28 | @ OAK | 72 | L 1-2 | 39-33 | 1 | 2,346 | Doyle Alexander | Steve Renko | Pete Broberg | Len Barker | | 284 | 260 | 24 |
| 1978-06-29 | @ OAK | 73 | L 7-8 | 39-34 | 1 | 3,380 | Fergie Jenkins | Tim Conroy | Dave Heaverlo | Paul Lindblad | | 291 | 268 | 23 |
| 1978-06-30 | @ CAL | 74 | L 2-4 | 39-35 | 1 | 21,654 | Jim Umbarger | Don Aase | Don Aase | Jim Umbarger | Dave LaRoche | 293 | 272 | 21 |
| 1978-07-01 | @ CAL | 75 | W 6-3 | 40-35 | 1 | 41,632 | Doc Medich | Frank Tanana | Doc Medich | Frank Tanana | Jon Matlack | 299 | 275 | 24 |
| 1978-07-02 | @ CAL | 76 | L 3-4 | 40-36 | 1 | 19,236 | Dock Ellis | Ken Brett | Dyar Miller | Steve Comer | | 302 | 279 | 23 |
| 1978-07-03 | @ CHA | 77 | L 6-7 | 40-37 | 2 | 42,231 | Doyle Alexander | Ken Kravec | Jim Willoughby | Reggie Cleveland | | 308 | 286 | 22 |
| 1978-07-04 | @ CHA | 78 | L 1-2 | 40-38 | 3 | 18,585 | Fergie Jenkins | Ron Schueler | Mike Proly | Fergie Jenkins | | 309 | 288 | 21 |
| 1978-07-05 | vs NYA | 79 | W 3-2 | 41-38 | 2 | 37,702 | Jon Matlack | Don Gullett | Jon Matlack | Don Gullett | | 312 | 290 | 22 |
| 1978-07-06 | vs NYA | 80 | L 2-7 | 41-39 | 3 | 37,930 | Doc Medich | Dick Tidrow | Dick Tidrow | Doc Medich | | 314 | 297 | 17 |
| 1978-07-07 | vs DET | 81 | L 7-12 | 41-40 | 3 | 21,069 | Dock Ellis | Dave Rozema | Dave Rozema | Dock Ellis | | 321 | 309 | 12 |
| 1978-07-08 | vs DET | 82 | L 1-5 | 41-41 | 4 | 22,993 | Doyle Alexander | Milt Wilcox | Milt Wilcox | Doyle Alexander | | 322 | 314 | 8 |
| 1978-07-09 | vs DET | 83 | W 4-3 | 42-41 | 3 | 15,770 | Fergie Jenkins | Steve Baker | Jim Umbarger | Jim Slaton | | 326 | 317 | 9 |
| 1978-07-13 | @ BOS | 84 | W 12-7 | 43-41 | 3 | 33,995 | Dock Ellis | Luis Tiant | Dock Ellis | Luis Tiant | | 338 | 324 | 14 |
| 1978-07-14 | @ BOS | 85 | W 4-3 | 44-41 | 3 | 32,899 | Fergie Jenkins | Mike Torrez | Fergie Jenkins | Mike Torrez | Reggie Cleveland | 342 | 327 | 15 |
| 1978-07-15 | @ BAL | 86 | L 7-8 | 45-42 | 3 | 0 | Doyle Alexander | Dennis Martinez | Tippy Martinez | Len Barker | | 349 | 335 | 14 |
| 1978-07-15 | @ BAL | 87 | W 11-1 | 45-42 | 3 | 22,353 | Doc Medich | Jim Palmer | Doc Medich | Jim Palmer | | 360 | 336 | 24 |
| 1978-07-16 | @ BAL | 88 | L 1-2 | 45-43 | 3 | 11,839 | Jon Matlack | Joe Kerrigan | Don Stanhouse | Reggie Cleveland | | 361 | 338 | 23 |
| 1978-07-17 | @ BAL | 89 | W 2-0 | 46-43 | 3 | 11,676 | Steve Comer | Mike Flanagan | Reggie Cleveland | Mike Flanagan | | 363 | 338 | 25 |
| 1978-07-18 | @ BAL | 90 | L 1-5 | 46-44 | 4 | 10,832 | Dock Ellis | Scott McGregor | Scott McGregor | Dock Ellis | | 364 | 343 | 21 |
| 1978-07-19 | @ KCA | 91 | L 4-11 | 46-45 | 4 | 28,420 | Fergie Jenkins | Rich Gale | Rich Gale | Fergie Jenkins | | 368 | 354 | 14 |
| 1978-07-20 | @ KCA | 92 | L 1-2 | 46-46 | 4 | 26,620 | Doyle Alexander | Dennis Leonard | Dennis Leonard | Doyle Alexander | | 369 | 356 | 13 |
| 1978-07-21 | vs MIL | 93 | L 3-4 | 46-47 | 4 | 28,419 | Doc Medich | Bill Travers | Bill Travers | Doc Medich | Bob McClure | 372 | 360 | 12 |
| 1978-07-22 | vs MIL | 94 | L 1-2 | 46-48 | 4 | 30,354 | Jon Matlack | Mike Caldwell | Mike Caldwell | Reggie Cleveland | | 373 | 362 | 11 |
| 1978-07-23 | vs MIL | 95 | L 8-17 | 46-49 | 4 | 11,615 | Steve Comer | Jerry Augustine | Andy Replogle | Steve Comer | | 381 | 379 | 2 |
| 1978-07-24 | vs BAL | 96 | L 6-10 | 46-50 | 4 | 11,732 | Fergie Jenkins | Dennis Martinez | Don Stanhouse | Fergie Jenkins | Scott McGregor | 387 | 389 | -2 |
| 1978-07-25 | vs BAL | 97 | L 6-7 | 46-51 | 4 | 12,686 | Doyle Alexander | Joe Kerrigan | Joe Kerrigan | Doyle Alexander | Tippy Martinez | 393 | 396 | -3 |
| 1978-07-26 | vs BOS | 98 | W 2-0 | 47-51 | 4 | 21,671 | Doc Medich | Dennis Eckersley | Doc Medich | Dennis Eckersley | | 395 | 396 | -1 |
| 1978-07-27 | vs BOS | 99 | W 3-1 | 48-51 | 4 | 29,684 | Jon Matlack | Luis Tiant | Jon Matlack | Luis Tiant | | 398 | 397 | 1 |
| 1978-07-28 | @ CHA | 100 | W 9-5 | 49-51 | 4 | 30,943 | Paul Mirabella | Ron Schueler | Paul Mirabella | Ron Schueler | | 407 | 402 | 5 |
| 1978-07-29 | @ CHA | 101 | L 2-6 | 49-52 | 4 | 27,662 | Fergie Jenkins | Steve Stone | Steve Stone | Fergie Jenkins | | 409 | 408 | 1 |
| 1978-07-30 | @ CHA | 102 | L 4-5 | 49-54 | 4 | 0 | Steve Comer | Wilbur Wood | Lerrin LaGrow | Reggie Cleveland | | 413 | 413 | 0 |
| 1978-07-30 | @ CHA | 103 | L 2-4 | 49-54 | 4 | 25,704 | Doyle Alexander | Francisco Barrios | Francisco Barrios | Doyle Alexander | Jim Willoughby | 415 | 417 | -2 |
| 1978-07-31 | @ NYA | 104 | L 1-6 | 49-55 | 4 | 15,419 | Doc Medich | Ed Figueroa | Ed Figueroa | Doc Medich | | 416 | 423 | -7 |
| 1978-08-01 | @ NYA | 105 | L 1-8 | 49-56 | 4 | 18,485 | Jon Matlack | Catfish Hunter | Catfish Hunter | Jon Matlack | | 417 | 431 | -14 |
| 1978-08-04 | vs CLE | 106 | W 8-0 | 50-56 | 4 | 20,307 | Fergie Jenkins | Rick Wise | Fergie Jenkins | Rick Wise | | 425 | 431 | -6 |
| 1978-08-05 | vs CLE | 107 | W 4-3 | 51-56 | 4 | 15,376 | Doyle Alexander | Mike Paxton | Steve Comer | Jim Kern | | 429 | 434 | -5 |
| 1978-08-06 | vs CLE | 108 | W 3-2 | 52-56 | 4 | 15,004 | Jon Matlack | Rick Waits | Jon Matlack | Rick Waits | | 432 | 436 | -4 |
| 1978-08-08 | @ DET | 109 | W 9-4 | 53-56 | 4 | 20,951 | Paul Mirabella | Dave Rozema | Paul Mirabella | Dave Rozema | Doc Medich | 441 | 440 | 1 |
| 1978-08-09 | @ DET | 110 | L 2-5 | 53-57 | 4 | 30,167 | Fergie Jenkins | Kip Young | Kip Young | Jim Umbarger | | 443 | 445 | -2 |
| 1978-08-11 | @ CLE | 111 | W 8-2 | 54-57 | 4 | 19,085 | Jon Matlack | Rick Waits | Jon Matlack | Rick Waits | | 451 | 447 | 4 |
| 1978-08-12 | @ CLE | 112 | W 6-1 | 55-57 | 4 | 13,783 | Doyle Alexander | David Clyde | Doyle Alexander | David Clyde | | 457 | 448 | 9 |
| 1978-08-13 | @ CLE | 113 | W 3-2 | 57-57 | 4 | 0 | Doc Medich | Dave Freisleben | Doc Medich | Dave Freisleben | Reggie Cleveland | 460 | 450 | 10 |
| 1978-08-13 | @ CLE | 114 | W 6-5 | 57-57 | 4 | 14,137 | Paul Mirabella | Rick Wise | Steve Comer | Rick Wise | Len Barker | 466 | 455 | 11 |
| 1978-08-14 | vs CHA | 115 | W 4-3 | 58-57 | 3 | 16,270 | Fergie Jenkins | Francisco Barrios | Fergie Jenkins | Francisco Barrios | | 470 | 458 | 12 |
| 1978-08-15 | vs CHA | 116 | W 1-0 | 59-57 | 3 | 18,665 | Jon Matlack | Steve Stone | Jon Matlack | Steve Stone | | 471 | 458 | 13 |
| 1978-08-16 | vs CHA | 117 | L 2-6 | 59-58 | 3 | 16,193 | Doyle Alexander | Ross Baumgarten | Ross Baumgarten | Doyle Alexander | Lerrin LaGrow | 473 | 464 | 9 |
| 1978-08-17 | vs CHA | 118 | L 2-4 | 59-59 | 3 | 17,158 | Paul Mirabella | Ken Kravec | Ken Kravec | Paul Mirabella | Lerrin LaGrow | 475 | 468 | 7 |
| 1978-08-18 | @ KCA | 119 | W 4-3 | 60-59 | 3 | 40,112 | Doc Medich | Rich Gale | Doc Medich | Rich Gale | | 479 | 471 | 8 |
| 1978-08-19 | @ KCA | 120 | L 0-3 | 60-60 | 3 | 37,604 | Fergie Jenkins | Dennis Leonard | Dennis Leonard | Fergie Jenkins | | 479 | 474 | 5 |
| 1978-08-20 | @ KCA | 121 | L 1-2 | 60-61 | 3 | 38,423 | Jon Matlack | Paul Splittorff | Paul Splittorff | Jon Matlack | | 480 | 476 | 4 |
| 1978-08-21 | @ TOR | 122 | L 6-8 | 60-62 | 3 | 16,001 | Dock Ellis | Balor Moore | Tom Murphy | Jim Umbarger | | 486 | 484 | 2 |
| 1978-08-22 | @ TOR | 123 | L 1-3 | 60-63 | 3 | 17,492 | Doc Medich | Jim Clancy | Jim Clancy | Doc Medich | Victor Cruz | 487 | 487 | 0 |
| 1978-08-23 | @ MIN | 124 | W 2-0 | 61-63 | 3 | 7,157 | Steve Comer | Roger Erickson | Steve Comer | Roger Erickson | | 489 | 487 | 2 |
| 1978-08-24 | @ MIN | 125 | W 4-1 | 62-63 | 3 | 8,666 | Fergie Jenkins | Dave Goltz | Fergie Jenkins | Dave Goltz | | 493 | 488 | 5 |
| 1978-08-25 | vs KCA | 126 | W 7-2 | 63-63 | 3 | 36,750 | Jon Matlack | Rich Gale | Jon Matlack | Rich Gale | | 500 | 490 | 10 |
| 1978-08-26 | vs KCA | 127 | W 8-4 | 64-63 | 3 | 33,084 | Dock Ellis | Larry Gura | Dock Ellis | Larry Gura | Len Barker | 508 | 494 | 14 |
| 1978-08-27 | vs KCA | 128 | L 2-4 | 64-64 | 3 | 25,242 | Doc Medich | Dennis Leonard | Dennis Leonard | Doc Medich | Al Hrabosky | 510 | 498 | 12 |
| 1978-08-28 | vs TOR | 129 | W 11-3 | 65-64 | 3 | 7,400 | Steve Comer | Tom Underwood | Steve Comer | Tom Underwood | Len Barker | 521 | 501 | 20 |
| 1978-08-29 | vs TOR | 130 | L 1-4 | 65-65 | 3 | 9,483 | Jon Matlack | Balor Moore | Balor Moore | Jon Matlack | | 522 | 505 | 17 |
| 1978-09-01 | @ MIL | 131 | W 5-4 | 66-65 | 3 | 13,648 | Fergie Jenkins | Lary Sorensen | Fergie Jenkins | Lary Sorensen | Reggie Cleveland | 527 | 509 | 18 |
| 1978-09-02 | @ MIL | 132 | L 6-10 | 66-66 | 3 | 17,795 | Doc Medich | Jerry Augustine | Bill Castro | Len Barker | | 533 | 519 | 14 |
| 1978-09-03 | @ MIL | 133 | L 3-4 | 66-67 | 3 | 14,014 | Jon Matlack | Andy Replogle | Ed Farmer | Jon Matlack | | 536 | 523 | 13 |
| 1978-09-04 | @ CAL | 134 | L 7-8 | 66-68 | 3 | 27,371 | Dock Ellis | Don Aase | Don Aase | Dock Ellis | Dave LaRoche | 543 | 531 | 12 |
| 1978-09-06 | @ CAL | 135 | W 11-5 | 68-68 | 3 | 0 | Steve Comer | Nolan Ryan | Steve Comer | Nolan Ryan | | 554 | 536 | 18 |
| 1978-09-06 | @ CAL | 136 | W 9-2 | 68-68 | 3 | 19,115 | Fergie Jenkins | Paul Hartzell | Fergie Jenkins | Paul Hartzell | | 563 | 538 | 25 |
| 1978-09-07 | @ CAL | 137 | L 6-7 | 68-69 | 3 | 15,815 | Doc Medich | Frank Tanana | Dyar Miller | Reggie Cleveland | Dave LaRoche | 569 | 545 | 24 |
| 1978-09-08 | @ OAK | 138 | L 4-11 | 68-70 | 3 | 9,841 | Jon Matlack | John Henry Johnson | Alan Wirth | Jon Matlack | | 573 | 556 | 17 |
| 1978-09-10 | @ OAK | 139 | W 8-3 | 69-71 | 3 | 0 | Doyle Alexander | Mike Norris | Doyle Alexander | Mike Norris | | 581 | 559 | 22 |
| 1978-09-10 | @ OAK | 140 | L 1-2 | 69-71 | 3 | 2,739 | Steve Comer | Pete Broberg | Pete Broberg | Steve Comer | | 582 | 561 | 21 |
| 1978-09-11 | vs CAL | 141 | W 1-0 | 70-71 | 3 | 7,245 | Fergie Jenkins | Paul Hartzell | Fergie Jenkins | Paul Hartzell | | 583 | 561 | 22 |
| 1978-09-12 | vs CAL | 142 | W 7-5 | 71-71 | 3 | 8,469 | Doc Medich | Frank Tanana | Doc Medich | Frank Tanana | Reggie Cleveland | 590 | 566 | 24 |
| 1978-09-13 | vs CAL | 143 | W 6-4 | 72-71 | 3 | 7,565 | Jon Matlack | Chris Knapp | Reggie Cleveland | Dave LaRoche | | 596 | 570 | 26 |
| 1978-09-14 | vs CAL | 144 | L 1-16 | 72-72 | 3 | 8,261 | Dock Ellis | Don Aase | Don Aase | Dock Ellis | | 597 | 586 | 11 |
| 1978-09-15 | vs OAK | 145 | L 0-1 | 73-73 | 3 | 0 | Doyle Alexander | Alan Wirth | Alan Wirth | Doyle Alexander | | 597 | 587 | 10 |
| 1978-09-15 | vs OAK | 146 | W 5-0 | 73-73 | 3 | 8,779 | Steve Comer | Pete Broberg | Steve Comer | Pete Broberg | | 602 | 587 | 15 |
| 1978-09-16 | vs OAK | 147 | W 8-1 | 74-73 | 3 | 14,948 | Fergie Jenkins | Matt Keough | Fergie Jenkins | Matt Keough | | 610 | 588 | 22 |
| 1978-09-17 | vs OAK | 148 | W 3-1 | 75-73 | 3 | 6,564 | Jon Matlack | Rick Langford | Jon Matlack | Rick Langford | | 613 | 589 | 24 |
| 1978-09-20 | @ MIN | 149 | L 3-5 | 75-74 | 3 | 2,736 | Steve Comer | Dave Goltz | Dave Goltz | Steve Comer | | 616 | 594 | 22 |
| 1978-09-21 | @ MIN | 150 | W 6-3 | 76-74 | 3 | 3,312 | Jon Matlack | Gary Serum | Jon Matlack | Gary Serum | | 622 | 597 | 25 |
| 1978-09-22 | vs SEA | 151 | W 10-2 | 78-74 | 3 | 0 | Doc Medich | Glenn Abbott | Doc Medich | Glenn Abbott | | 632 | 599 | 33 |
| 1978-09-22 | vs SEA | 152 | W 1-0 | 78-74 | 3 | 7,861 | Fergie Jenkins | Byron McLaughlin | Fergie Jenkins | Byron McLaughlin | | 633 | 599 | 34 |
| 1978-09-23 | vs SEA | 153 | W 7-2 | 79-74 | 3 | 10,526 | Doyle Alexander | Paul Mitchell | Doyle Alexander | Paul Mitchell | | 640 | 601 | 39 |
| 1978-09-24 | vs SEA | 154 | W 5-3 | 81-74 | 3 | 0 | Steve Comer | Jim Colborn | Steve Comer | Jim Colborn | Paul Mirabella | 645 | 604 | 41 |
| 1978-09-24 | vs SEA | 155 | W 4-3 | 81-74 | 3 | 6,955 | Danny Darwin | Rick Jones | Danny Darwin | Rick Jones | Jim Umbarger | 649 | 607 | 42 |
| 1978-09-25 | vs MIN | 156 | W 3-2 | 82-74 | 3 | 6,404 | Jon Matlack | Gary Serum | Reggie Cleveland | Mike Marshall | | 652 | 609 | 43 |
| 1978-09-26 | vs MIN | 157 | L 2-6 | 82-75 | 3 | 6,797 | Doc Medich | Geoff Zahn | Mike Marshall | Paul Mirabella | | 654 | 615 | 39 |
| 1978-09-27 | vs MIN | 158 | W 10-5 | 83-75 | 3 | 9,601 | Fergie Jenkins | Roger Erickson | Paul Mirabella | Stan Perzanowski | | 664 | 620 | 44 |
| 1978-09-28 | @ SEA | 159 | W 4-3 | 84-75 | 3 | 4,768 | Doyle Alexander | Shane Rawley | Jim Umbarger | Shane Rawley | | 668 | 623 | 45 |
| 1978-09-29 | @ SEA | 160 | W 11-4 | 85-75 | 3 | 5,998 | Steve Comer | Mike Parrott | Steve Comer | Mike Parrott | | 679 | 627 | 52 |
| 1978-09-30 | @ SEA | 161 | W 4-1 | 86-75 | 2 | 12,132 | Jon Matlack | Rick Jones | Jon Matlack | Rick Jones | | 683 | 628 | 55 |
| 1978-10-01 | @ SEA | 162 | W 9-4 | 87-75 | 2 | 5,807 | Fergie Jenkins | Glenn Abbott | Fergie Jenkins | Glenn Abbott | | 692 | 632 | 60 |