| 1978-04-07 | @ DET | 1 | L 2-6 | 0-1 | 7 | 52,528 | Dave Lemanczyk | Mark Fidrych | Mark Fidrych | Dave Lemanczyk | | 2 | 6 | -4 |
| 1978-04-08 | @ DET | 2 | W 5-2 | 1-1 | 4 | 12,413 | Jerry Garvin | Jim Slaton | Jerry Garvin | Jim Slaton | Mike Willis | 7 | 8 | -1 |
| 1978-04-09 | @ DET | 3 | L 4-8 | 1-2 | 6 | 9,169 | Tom Underwood | Jack Billingham | Jack Billingham | Tom Underwood | Steve Foucault | 11 | 16 | -5 |
| 1978-04-11 | @ CHA | 4 | L 5-9 | 1-3 | 6 | 3,347 | Jesse Jefferson | Ken Kravec | Ken Kravec | Jesse Jefferson | Pablo Torrealba | 16 | 25 | -9 |
| 1978-04-12 | @ CHA | 5 | L 4-5 | 1-4 | 6 | 5,742 | Dave Lemanczyk | Steve Stone | Steve Stone | Dave Lemanczyk | Lerrin LaGrow | 20 | 30 | -10 |
| 1978-04-14 | vs DET | 6 | W 10-8 | 2-4 | 6 | 35,761 | Jerry Garvin | Jim Slaton | Don Kirkwood | Milt Wilcox | Tom Murphy | 30 | 38 | -8 |
| 1978-04-15 | vs DET | 7 | L 3-6 | 2-5 | 7 | 15,024 | Tom Underwood | Jack Billingham | Jack Billingham | Mike Willis | Steve Foucault | 33 | 44 | -11 |
| 1978-04-16 | vs DET | 8 | L 3-4 | 2-6 | 7 | 17,088 | Jim Clancy | Dave Rozema | Jim Crawford | Jim Clancy | | 36 | 48 | -12 |
| 1978-04-17 | vs KCA | 9 | L 1-3 | 2-7 | 7 | 10,169 | Jesse Jefferson | Larry Gura | Larry Gura | Jesse Jefferson | Al Hrabosky | 37 | 51 | -14 |
| 1978-04-18 | vs KCA | 10 | L 0-5 | 2-8 | 7 | 10,218 | Dave Lemanczyk | Paul Splittorff | Paul Splittorff | Dave Lemanczyk | | 37 | 56 | -19 |
| 1978-04-19 | vs NYA | 11 | W 4-3 | 3-8 | 7 | 13,306 | Jerry Garvin | Ken Holtzman | Tom Murphy | Rich Gossage | | 41 | 59 | -18 |
| 1978-04-21 | vs CHA | 12 | L 2-11 | 3-9 | 7 | 10,108 | Tom Underwood | Francisco Barrios | Francisco Barrios | Tom Underwood | Lerrin LaGrow | 43 | 70 | -27 |
| 1978-04-22 | vs CHA | 13 | W 4-2 | 4-9 | 7 | 44,327 | Jim Clancy | Wilbur Wood | Jim Clancy | Wilbur Wood | Mike Willis | 47 | 72 | -25 |
| 1978-04-23 | vs CHA | 14 | W 4-0 | 5-9 | 7 | 17,427 | Jesse Jefferson | Steve Stone | Jesse Jefferson | Steve Stone | | 51 | 72 | -21 |
| 1978-04-24 | vs CLE | 15 | L 2-4 | 5-10 | 7 | 10,776 | Dave Lemanczyk | Don Hood | Don Hood | Dave Lemanczyk | Jim Kern | 53 | 76 | -23 |
| 1978-04-25 | vs CLE | 16 | L 5-6 | 5-11 | 7 | 11,348 | Jerry Garvin | Wayne Garland | Wayne Garland | Jerry Garvin | Dennis Kinney | 58 | 82 | -24 |
| 1978-04-26 | @ KCA | 17 | W 3-1 | 6-11 | 6 | 19,545 | Tom Underwood | Paul Splittorff | Tom Murphy | Paul Splittorff | | 61 | 83 | -22 |
| 1978-04-27 | @ KCA | 18 | W 8-7 | 7-11 | 6 | 17,422 | Jim Clancy | Larry Gura | Balor Moore | Doug Bird | Mike Willis | 69 | 90 | -21 |
| 1978-04-28 | @ CAL | 19 | L 4-5 | 7-12 | 6 | 16,575 | Jesse Jefferson | Don Aase | Dyar Miller | Jesse Jefferson | Dave LaRoche | 73 | 95 | -22 |
| 1978-04-29 | @ CAL | 20 | L 0-5 | 7-13 | 7 | 24,354 | Dave Lemanczyk | Nolan Ryan | Nolan Ryan | Dave Lemanczyk | | 73 | 100 | -27 |
| 1978-04-30 | @ CAL | 21 | W 9-3 | 8-13 | 7 | 27,367 | Jerry Garvin | Chris Knapp | Jerry Garvin | Chris Knapp | | 82 | 103 | -21 |
| 1978-05-02 | @ OAK | 22 | L 1-2 | 8-14 | 7 | 5,663 | Tom Underwood | Matt Keough | Matt Keough | Tom Underwood | Elias Sosa | 83 | 105 | -22 |
| 1978-05-03 | @ OAK | 23 | L 3-11 | 8-15 | 7 | 2,512 | Jim Clancy | Pete Broberg | Pete Broberg | Jim Clancy | Bob Lacey | 86 | 116 | -30 |
| 1978-05-05 | @ SEA | 24 | L 1-9 | 8-16 | 7 | 4,824 | Jesse Jefferson | Rick Honeycutt | Rick Honeycutt | Jesse Jefferson | | 87 | 125 | -38 |
| 1978-05-06 | @ SEA | 25 | L 0-6 | 8-17 | 7 | 7,589 | Dave Lemanczyk | Paul Mitchell | Paul Mitchell | Dave Lemanczyk | | 87 | 131 | -44 |
| 1978-05-07 | @ SEA | 26 | L 7-9 | 8-18 | 7 | 12,489 | Jerry Garvin | Dick Pole | Enrique Romo | Mike Willis | | 94 | 140 | -46 |
| 1978-05-09 | vs OAK | 27 | W 4-0 | 9-18 | 7 | 11,339 | Tom Underwood | Pete Broberg | Tom Underwood | Pete Broberg | | 98 | 140 | -42 |
| 1978-05-10 | vs OAK | 28 | W 3-1 | 10-18 | 7 | 21,766 | Jim Clancy | Rick Langford | Jim Clancy | Rick Langford | | 101 | 141 | -40 |
| 1978-05-12 | vs SEA | 29 | W 8-3 | 11-18 | 7 | 11,518 | Jesse Jefferson | Paul Mitchell | Jesse Jefferson | Shane Rawley | | 109 | 144 | -35 |
| 1978-05-13 | vs SEA | 30 | L 6-9 | 11-19 | 7 | 21,350 | Dave Lemanczyk | Dick Pole | Dick Pole | Dave Lemanczyk | Enrique Romo | 115 | 153 | -38 |
| 1978-05-15 | vs CAL | 31 | W 10-6 | 12-19 | 7 | 11,295 | Jerry Garvin | Ken Brett | Balor Moore | Paul Hartzell | | 125 | 159 | -34 |
| 1978-05-16 | vs CAL | 32 | W 5-4 | 13-19 | 7 | 12,044 | Tom Underwood | Don Aase | Mike Willis | Don Aase | Tom Murphy | 130 | 163 | -33 |
| 1978-05-18 | @ BAL | 33 | L 3-5 | 13-20 | 7 | 4,255 | Jim Clancy | Mike Flanagan | Mike Flanagan | Jim Clancy | | 133 | 168 | -35 |
| 1978-05-19 | vs NYA | 34 | L 3-11 | 13-21 | 7 | 26,025 | Jesse Jefferson | Dick Tidrow | Dick Tidrow | Jesse Jefferson | | 136 | 179 | -43 |
| 1978-05-20 | vs NYA | 35 | W 10-8 | 14-21 | 7 | 30,550 | Dave Lemanczyk | Jim Beattie | Dave Lemanczyk | Ken Clay | | 146 | 187 | -41 |
| 1978-05-21 | vs NYA | 36 | L 1-2 | 14-23 | 7 | 0 | Tom Underwood | Ed Figueroa | Ed Figueroa | Tom Underwood | Rich Gossage | 147 | 189 | -42 |
| 1978-05-21 | vs NYA | 37 | L 1-9 | 14-23 | 7 | 41,308 | Jerry Garvin | Ken Clay | Ken Clay | Jerry Garvin | | 148 | 198 | -50 |
| 1978-05-22 | vs BOS | 38 | L 4-5 | 14-24 | 7 | 25,054 | Jim Clancy | Allen Ripley | Allen Ripley | Jim Clancy | Bob Stanley | 152 | 203 | -51 |
| 1978-05-23 | vs BOS | 39 | W 2-1 | 15-24 | 7 | 14,578 | Jesse Jefferson | Jim Wright | Jesse Jefferson | Bill Campbell | | 154 | 204 | -50 |
| 1978-05-24 | vs BOS | 40 | L 2-8 | 15-25 | 7 | 28,825 | Dave Lemanczyk | Mike Torrez | Mike Torrez | Dave Lemanczyk | | 156 | 212 | -56 |
| 1978-05-25 | vs BOS | 41 | L 5-9 | 15-26 | 7 | 17,197 | Tom Underwood | Dennis Eckersley | Dennis Eckersley | Tom Underwood | Dick Drago | 161 | 221 | -60 |
| 1978-05-26 | @ NYA | 42 | L 3-4 | 15-27 | 7 | 24,171 | Jerry Garvin | Jim Beattie | Sparky Lyle | Jerry Garvin | | 164 | 225 | -61 |
| 1978-05-27 | @ NYA | 43 | W 4-1 | 16-27 | 7 | 56,078 | Jim Clancy | Ed Figueroa | Jim Clancy | Ed Figueroa | Tom Murphy | 168 | 226 | -58 |
| 1978-05-28 | @ NYA | 44 | L 3-5 | 16-29 | 7 | 41,534 | Jesse Jefferson | Ron Guidry | Ron Guidry | Jesse Jefferson | | 171 | 231 | -60 |
| 1978-05-28 | @ NYA | 45 | L 5-6 | 16-29 | 7 | 42,344 | Dave Lemanczyk | Ken Clay | Rich Gossage | Tom Murphy | | 176 | 237 | -61 |
| 1978-05-29 | @ BOS | 46 | L 4-5 | 16-30 | 7 | 25,935 | Tom Underwood | Mike Torrez | Mike Torrez | Tom Underwood | | 180 | 242 | -62 |
| 1978-05-30 | @ BOS | 47 | L 0-4 | 16-31 | 7 | 25,853 | Jerry Garvin | Dennis Eckersley | Dennis Eckersley | Jerry Garvin | | 180 | 246 | -66 |
| 1978-05-31 | @ BOS | 48 | W 6-2 | 17-31 | 7 | 27,945 | Jim Clancy | Bill Lee | Jim Clancy | Bill Lee | | 186 | 248 | -62 |
| 1978-06-02 | vs TEX | 49 | W 3-1 | 18-31 | 7 | 25,273 | Jesse Jefferson | Jon Matlack | Jesse Jefferson | Jon Matlack | | 189 | 249 | -60 |
| 1978-06-03 | vs TEX | 50 | W 4-3 | 19-31 | 7 | 32,021 | Tom Underwood | Jim Umbarger | Tom Underwood | Jim Umbarger | Tom Murphy | 193 | 252 | -59 |
| 1978-06-04 | vs TEX | 51 | L 5-9 | 19-32 | 7 | 28,374 | Dave Lemanczyk | Dock Ellis | Dock Ellis | Dave Lemanczyk | Steve Comer | 198 | 261 | -63 |
| 1978-06-09 | @ MIL | 52 | L 2-3 | 19-33 | 7 | 9,959 | Jim Clancy | Mike Caldwell | Mike Caldwell | Tom Murphy | | 200 | 264 | -64 |
| 1978-06-10 | @ MIL | 53 | L 0-5 | 19-34 | 7 | 25,889 | Jerry Garvin | Bill Travers | Bill Travers | Jerry Garvin | | 200 | 269 | -69 |
| 1978-06-11 | @ MIL | 54 | L 1-2 | 19-36 | 7 | 0 | Tom Underwood | Lary Sorensen | Lary Sorensen | Tom Underwood | | 201 | 271 | -70 |
| 1978-06-11 | @ MIL | 55 | L 4-5 | 19-36 | 7 | 21,568 | Jesse Jefferson | Andy Replogle | Randy Stein | Tom Murphy | | 205 | 276 | -71 |
| 1978-06-13 | vs MIN | 56 | L 0-2 | 19-38 | 7 | 0 | Balor Moore | Dave Goltz | Dave Goltz | Balor Moore | Mike Marshall | 205 | 278 | -73 |
| 1978-06-13 | vs MIN | 57 | L 2-7 | 19-38 | 7 | 14,489 | Jim Clancy | Geoff Zahn | Geoff Zahn | Jim Clancy | | 207 | 285 | -78 |
| 1978-06-14 | vs MIL | 58 | L 5-7 | 19-40 | 7 | 0 | Don Kirkwood | Bill Travers | Bill Castro | Tom Murphy | | 212 | 292 | -80 |
| 1978-06-14 | vs MIL | 59 | L 0-5 | 19-40 | 7 | 28,346 | Jerry Garvin | Jerry Augustine | Jerry Augustine | Jerry Garvin | | 212 | 297 | -85 |
| 1978-06-16 | @ TEX | 60 | W 8-3 | 21-40 | 7 | 0 | Tom Underwood | Dock Ellis | Tom Underwood | Dock Ellis | | 220 | 300 | -80 |
| 1978-06-16 | @ TEX | 61 | W 5-2 | 21-40 | 7 | 20,660 | Jesse Jefferson | Roger Moret | Jesse Jefferson | Roger Moret | Tom Murphy | 225 | 302 | -77 |
| 1978-06-17 | @ TEX | 62 | L 2-13 | 21-41 | 7 | 30,033 | Jim Clancy | Fergie Jenkins | Fergie Jenkins | Jim Clancy | | 227 | 315 | -88 |
| 1978-06-18 | @ TEX | 63 | L 2-3 | 21-42 | 7 | 24,645 | Balor Moore | Doyle Alexander | Reggie Cleveland | Tom Murphy | | 229 | 318 | -89 |
| 1978-06-20 | vs DET | 64 | L 3-4 | 21-43 | 7 | 31,625 | Jerry Garvin | Steve Baker | John Hiller | Mike Willis | | 232 | 322 | -90 |
| 1978-06-21 | vs DET | 65 | L 8-10 | 21-44 | 7 | 29,439 | Tom Underwood | Jack Billingham | Jim Crawford | Don Kirkwood | Steve Foucault | 240 | 332 | -92 |
| 1978-06-23 | @ CLE | 66 | L 3-8 | 21-45 | 7 | 6,514 | Jesse Jefferson | Rick Waits | Rick Waits | Jesse Jefferson | | 243 | 340 | -97 |
| 1978-06-24 | @ CLE | 67 | L 3-12 | 21-46 | 7 | 7,176 | Jim Clancy | Mike Paxton | Mike Paxton | Jim Clancy | | 246 | 352 | -106 |
| 1978-06-25 | @ CLE | 68 | W 2-1 | 22-47 | 7 | 0 | Balor Moore | David Clyde | Balor Moore | David Clyde | Victor Cruz | 248 | 353 | -105 |
| 1978-06-25 | @ CLE | 69 | L 2-3 | 22-47 | 7 | 21,959 | Jerry Garvin | Rick Wise | Rick Wise | Jerry Garvin | Sid Monge | 250 | 356 | -106 |
| 1978-06-26 | vs BAL | 70 | W 24-10 | 23-47 | 7 | 16,184 | Tom Underwood | Mike Flanagan | Tom Underwood | Mike Flanagan | | 274 | 366 | -92 |
| 1978-06-27 | vs BAL | 71 | W 6-2 | 25-47 | 7 | 0 | Dave Lemanczyk | Jim Palmer | Dave Lemanczyk | Jim Palmer | Victor Cruz | 280 | 368 | -88 |
| 1978-06-27 | vs BAL | 72 | W 9-8 | 25-47 | 7 | 38,563 | Jesse Jefferson | Nelson Briles | Victor Cruz | Don Stanhouse | | 289 | 376 | -87 |
| 1978-06-28 | vs BAL | 73 | W 3-2 | 26-47 | 7 | 28,392 | Jim Clancy | Scott McGregor | Jim Clancy | Scott McGregor | Tom Murphy | 292 | 378 | -86 |
| 1978-06-30 | vs CLE | 74 | L 0-3 | 26-48 | 7 | 16,129 | Jerry Garvin | Rick Wise | Rick Wise | Jerry Garvin | | 292 | 381 | -89 |
| 1978-07-01 | vs CLE | 75 | W 9-3 | 27-48 | 7 | 19,277 | Tom Underwood | Don Hood | Tom Underwood | Don Hood | Victor Cruz | 301 | 384 | -83 |
| 1978-07-02 | vs CLE | 76 | L 0-2 | 28-49 | 7 | 0 | Dave Lemanczyk | Rick Waits | Rick Waits | Dave Lemanczyk | Jim Kern | 301 | 386 | -85 |
| 1978-07-02 | vs CLE | 77 | W 3-1 | 28-49 | 7 | 28,305 | Jesse Jefferson | Dave Freisleben | Jesse Jefferson | Dave Freisleben | | 304 | 387 | -83 |
| 1978-07-03 | @ DET | 78 | L 5-6 | 28-50 | 7 | 21,597 | Jim Clancy | Milt Wilcox | Milt Wilcox | Tom Murphy | | 309 | 393 | -84 |
| 1978-07-04 | @ DET | 79 | W 9-2 | 29-50 | 7 | 11,913 | Balor Moore | Jack Morris | Balor Moore | Jack Morris | | 318 | 395 | -77 |
| 1978-07-05 | @ BAL | 80 | L 1-3 | 29-52 | 7 | 0 | Jerry Garvin | Mike Flanagan | Mike Flanagan | Jerry Garvin | | 319 | 398 | -79 |
| 1978-07-05 | @ BAL | 81 | L 6-8 | 29-52 | 7 | 9,886 | Tom Underwood | Nelson Briles | Joe Kerrigan | Tom Murphy | | 325 | 406 | -81 |
| 1978-07-06 | @ BAL | 82 | W 2-0 | 30-52 | 7 | 14,926 | Dave Lemanczyk | Jim Palmer | Dave Lemanczyk | Jim Palmer | Mike Willis | 327 | 406 | -79 |
| 1978-07-07 | @ CHA | 83 | W 3-2 | 31-52 | 7 | 18,643 | Jesse Jefferson | Francisco Barrios | Joe Coleman | Rich Hinton | Victor Cruz | 330 | 408 | -78 |
| 1978-07-08 | @ CHA | 84 | W 3-0 | 32-52 | 7 | 23,648 | Jim Clancy | Ken Kravec | Jim Clancy | Ken Kravec | Mike Willis | 333 | 408 | -75 |
| 1978-07-09 | @ CHA | 85 | L 3-5 | 32-53 | 7 | 16,493 | Balor Moore | Steve Stone | Steve Stone | Tom Underwood | Jim Willoughby | 336 | 413 | -77 |
| 1978-07-13 | @ CAL | 86 | L 0-5 | 32-54 | 7 | 16,625 | Dave Lemanczyk | Don Aase | Don Aase | Dave Lemanczyk | | 336 | 418 | -82 |
| 1978-07-14 | @ CAL | 87 | L 2-3 | 32-55 | 7 | 20,338 | Jesse Jefferson | Nolan Ryan | Dyar Miller | Mike Willis | | 338 | 421 | -83 |
| 1978-07-15 | @ OAK | 88 | L 2-3 | 32-56 | 7 | 6,863 | Tom Underwood | Steve Renko | Elias Sosa | Tom Underwood | | 340 | 424 | -84 |
| 1978-07-16 | @ OAK | 89 | L 5-8 | 32-57 | 7 | 3,753 | Jim Clancy | Pete Broberg | Elias Sosa | Mike Willis | Dave Heaverlo | 345 | 432 | -87 |
| 1978-07-17 | @ OAK | 90 | L 3-5 | 32-58 | 7 | 12,414 | Jerry Garvin | John Henry Johnson | John Henry Johnson | Jerry Garvin | | 348 | 437 | -89 |
| 1978-07-18 | @ SEA | 91 | W 13-12 | 33-58 | 7 | 6,881 | Dave Lemanczyk | Glenn Abbott | Tom Murphy | Dick Pole | | 361 | 449 | -88 |
| 1978-07-19 | @ SEA | 92 | L 2-6 | 33-59 | 7 | 7,434 | Jesse Jefferson | Rick Honeycutt | Rick Honeycutt | Jesse Jefferson | John Montague | 363 | 455 | -92 |
| 1978-07-21 | vs OAK | 93 | L 2-7 | 34-60 | 7 | 0 | Balor Moore | Steve Renko | Steve Renko | Balor Moore | | 365 | 462 | -97 |
| 1978-07-21 | vs OAK | 94 | W 5-4 | 34-60 | 7 | 21,050 | Tom Underwood | Pete Broberg | Tom Murphy | Bob Lacey | Victor Cruz | 370 | 466 | -96 |
| 1978-07-22 | vs OAK | 95 | W 7-3 | 35-60 | 7 | 21,028 | Jim Clancy | John Henry Johnson | Jim Clancy | John Henry Johnson | | 377 | 469 | -92 |
| 1978-07-23 | vs OAK | 96 | L 3-5 | 35-61 | 7 | 23,153 | Jerry Garvin | Rick Langford | Rick Langford | Jerry Garvin | Dave Heaverlo | 380 | 474 | -94 |
| 1978-07-24 | vs SEA | 97 | L 0-1 | 35-63 | 7 | 0 | Dave Lemanczyk | Rick Honeycutt | Rick Honeycutt | Dave Lemanczyk | | 380 | 475 | -95 |
| 1978-07-24 | vs SEA | 98 | L 2-7 | 35-63 | 7 | 16,291 | Jesse Jefferson | Jim Colborn | Jim Colborn | Jesse Jefferson | Enrique Romo | 382 | 482 | -100 |
| 1978-07-25 | vs SEA | 99 | L 2-4 | 35-64 | 7 | 14,103 | Tom Underwood | Glenn Abbott | Glenn Abbott | Tom Underwood | | 384 | 486 | -102 |
| 1978-07-26 | @ MIN | 100 | W 5-1 | 36-64 | 7 | 6,014 | Balor Moore | Dave Goltz | Balor Moore | Dave Goltz | | 389 | 487 | -98 |
| 1978-07-27 | @ MIN | 101 | L 3-6 | 36-65 | 7 | 18,285 | Jim Clancy | Stan Perzanowski | Stan Perzanowski | Jim Clancy | | 392 | 493 | -101 |
| 1978-07-28 | vs MIL | 102 | W 3-2 | 37-65 | 7 | 17,060 | Jesse Jefferson | Jerry Augustine | Victor Cruz | Bill Castro | | 395 | 495 | -100 |
| 1978-07-29 | vs MIL | 103 | W 4-3 | 38-65 | 7 | 25,037 | Dave Lemanczyk | Lary Sorensen | Dave Lemanczyk | Lary Sorensen | Victor Cruz | 399 | 498 | -99 |
| 1978-07-30 | vs MIL | 104 | L 5-10 | 38-66 | 7 | 21,511 | Tom Underwood | Eduardo Rodriguez | Randy Stein | Tom Murphy | | 404 | 508 | -104 |
| 1978-07-31 | vs DET | 105 | W 8-7 | 39-66 | 7 | 18,032 | Balor Moore | Jack Billingham | Joe Coleman | Bob Sykes | | 412 | 515 | -103 |
| 1978-08-01 | vs DET | 106 | L 2-3 | 39-67 | 7 | 19,265 | Jim Clancy | Jim Slaton | Jim Slaton | Jim Clancy | | 414 | 518 | -104 |
| 1978-08-04 | @ KCA | 107 | W 5-4 | 40-67 | 7 | 35,064 | Jesse Jefferson | Paul Splittorff | Victor Cruz | Al Hrabosky | | 419 | 522 | -103 |
| 1978-08-05 | @ KCA | 108 | L 3-5 | 40-68 | 7 | 34,179 | Dave Lemanczyk | Larry Gura | Larry Gura | Dave Lemanczyk | Steve Mingori | 422 | 527 | -105 |
| 1978-08-06 | @ KCA | 109 | L 5-12 | 40-69 | 7 | 35,404 | Balor Moore | Rich Gale | Rich Gale | Balor Moore | | 427 | 539 | -112 |
| 1978-08-07 | vs BAL | 110 | W 2-1 | 41-69 | 7 | 19,184 | Jim Clancy | Dennis Martinez | Jim Clancy | Dennis Martinez | | 429 | 540 | -111 |
| 1978-08-08 | vs BAL | 111 | W 5-3 | 42-69 | 7 | 19,052 | Tom Underwood | Mike Flanagan | Tom Underwood | Mike Flanagan | Victor Cruz | 434 | 543 | -109 |
| 1978-08-09 | vs CHA | 112 | W 8-0 | 43-69 | 7 | 24,282 | Jesse Jefferson | Steve Stone | Jesse Jefferson | Steve Stone | | 442 | 543 | -101 |
| 1978-08-10 | vs CHA | 113 | W 7-3 | 44-69 | 7 | 15,508 | Jerry Garvin | Wilbur Wood | Jerry Garvin | Wilbur Wood | Victor Cruz | 449 | 546 | -97 |
| 1978-08-11 | vs KCA | 114 | L 8-9 | 44-70 | 7 | 20,602 | Balor Moore | Dennis Leonard | Al Hrabosky | Victor Cruz | | 457 | 555 | -98 |
| 1978-08-12 | vs KCA | 115 | W 5-2 | 45-70 | 7 | 23,132 | Jim Clancy | Paul Splittorff | Jim Clancy | Paul Splittorff | | 462 | 557 | -95 |
| 1978-08-13 | vs KCA | 116 | W 3-2 | 46-70 | 7 | 30,270 | Tom Underwood | Larry Gura | Mike Willis | Al Hrabosky | | 465 | 559 | -94 |
| 1978-08-15 | @ MIL | 117 | L 1-9 | 46-71 | 7 | 0 | Dave Lemanczyk | Jerry Augustine | Jerry Augustine | Dave Lemanczyk | | 466 | 568 | -102 |
| 1978-08-16 | @ MIL | 118 | L 1-8 | 46-73 | 7 | 0 | Jesse Jefferson | Mike Caldwell | Mike Caldwell | Jesse Jefferson | | 467 | 576 | -109 |
| 1978-08-16 | @ MIL | 119 | L 2-3 | 46-73 | 7 | 16,920 | Balor Moore | Eduardo Rodriguez | Eduardo Rodriguez | Balor Moore | Bob McClure | 469 | 579 | -110 |
| 1978-08-17 | @ MIL | 120 | L 0-6 | 46-74 | 7 | 18,829 | Jim Clancy | Bill Travers | Bill Travers | Jim Clancy | | 469 | 585 | -116 |
| 1978-08-18 | @ MIN | 121 | L 3-4 | 46-75 | 7 | 4,599 | Tom Underwood | Dave Goltz | Jeff Holly | Tom Murphy | | 472 | 589 | -117 |
| 1978-08-19 | @ MIN | 122 | L 0-5 | 46-76 | 7 | 10,745 | Jerry Garvin | Gary Serum | Gary Serum | Jerry Garvin | | 472 | 594 | -122 |
| 1978-08-20 | @ MIN | 123 | W 6-2 | 47-76 | 7 | 11,685 | Don Kirkwood | Stan Perzanowski | Don Kirkwood | Stan Perzanowski | Tom Murphy | 478 | 596 | -118 |
| 1978-08-21 | vs TEX | 124 | W 8-6 | 48-76 | 7 | 16,001 | Balor Moore | Dock Ellis | Tom Murphy | Jim Umbarger | | 486 | 602 | -116 |
| 1978-08-22 | vs TEX | 125 | W 3-1 | 49-76 | 7 | 17,492 | Jim Clancy | Doc Medich | Jim Clancy | Doc Medich | Victor Cruz | 489 | 603 | -114 |
| 1978-08-23 | @ DET | 126 | W 4-3 | 51-76 | 7 | 0 | Tom Underwood | Dave Rozema | Victor Cruz | Dave Rozema | | 493 | 606 | -113 |
| 1978-08-23 | @ DET | 127 | W 5-4 | 51-76 | 7 | 26,631 | Jerry Garvin | Bob Sykes | Jerry Garvin | Bob Sykes | Mike Willis | 498 | 610 | -112 |
| 1978-08-24 | @ DET | 128 | L 2-5 | 51-77 | 7 | 13,314 | Balor Moore | Milt Wilcox | Milt Wilcox | Balor Moore | | 500 | 615 | -115 |
| 1978-08-25 | vs MIN | 129 | W 7-3 | 52-77 | 7 | 15,206 | Don Kirkwood | Gary Serum | Don Kirkwood | Gary Serum | Mike Willis | 507 | 618 | -111 |
| 1978-08-26 | vs MIN | 130 | W 4-3 | 53-77 | 7 | 25,601 | Jesse Jefferson | Geoff Zahn | Victor Cruz | Geoff Zahn | | 511 | 621 | -110 |
| 1978-08-27 | vs MIN | 131 | L 2-3 | 53-78 | 7 | 22,023 | Jim Clancy | Roger Erickson | Mike Marshall | Mike Willis | | 513 | 624 | -111 |
| 1978-08-28 | @ TEX | 132 | L 3-11 | 53-79 | 7 | 7,400 | Tom Underwood | Steve Comer | Steve Comer | Tom Underwood | Len Barker | 516 | 635 | -119 |
| 1978-08-29 | @ TEX | 133 | W 4-1 | 54-79 | 7 | 9,483 | Balor Moore | Jon Matlack | Balor Moore | Jon Matlack | | 520 | 636 | -116 |
| 1978-08-30 | @ BOS | 134 | L 1-2 | 55-80 | 7 | 0 | Don Kirkwood | Dennis Eckersley | Dennis Eckersley | Don Kirkwood | | 521 | 638 | -117 |
| 1978-08-30 | @ BOS | 135 | W 7-6 | 55-80 | 7 | 32,825 | Jerry Garvin | Andy Hassler | Victor Cruz | Bob Stanley | | 528 | 644 | -116 |
| 1978-09-01 | vs CAL | 136 | L 4-6 | 55-81 | 7 | 16,757 | Jesse Jefferson | Paul Hartzell | Paul Hartzell | Jesse Jefferson | Dave LaRoche | 532 | 650 | -118 |
| 1978-09-02 | vs CAL | 137 | L 0-2 | 55-82 | 7 | 21,099 | Jim Clancy | Frank Tanana | Frank Tanana | Jim Clancy | | 532 | 652 | -120 |
| 1978-09-03 | vs CAL | 138 | L 1-3 | 55-83 | 7 | 20,054 | Tom Underwood | Chris Knapp | Chris Knapp | Tom Underwood | | 533 | 655 | -122 |
| 1978-09-04 | vs CLE | 139 | L 4-5 | 55-84 | 7 | 14,364 | Balor Moore | Mike Paxton | Mike Paxton | Balor Moore | | 537 | 660 | -123 |
| 1978-09-05 | vs CLE | 140 | L 2-6 | 55-85 | 7 | 11,060 | Don Kirkwood | Rick Waits | Rick Waits | Don Kirkwood | | 539 | 666 | -127 |
| 1978-09-06 | vs MIL | 141 | L 0-7 | 55-86 | 7 | 21,390 | Jesse Jefferson | Lary Sorensen | Lary Sorensen | Jesse Jefferson | | 539 | 673 | -134 |
| 1978-09-07 | vs MIL | 142 | W 5-4 | 56-86 | 7 | 12,092 | Jim Clancy | Jerry Augustine | Victor Cruz | Bob McClure | | 544 | 677 | -133 |
| 1978-09-08 | vs BAL | 143 | L 4-5 | 56-87 | 7 | 14,155 | Tom Underwood | Mike Flanagan | Nelson Briles | Tom Underwood | Don Stanhouse | 548 | 682 | -134 |
| 1978-09-09 | vs BAL | 144 | L 0-4 | 56-88 | 7 | 29,255 | Balor Moore | Scott McGregor | Scott McGregor | Balor Moore | | 548 | 686 | -138 |
| 1978-09-11 | @ CLE | 145 | L 4-6 | 57-89 | 7 | 0 | Jesse Jefferson | Rick Waits | Rick Waits | Jesse Jefferson | | 552 | 692 | -140 |
| 1978-09-11 | @ CLE | 146 | W 7-1 | 57-89 | 7 | 3,356 | Don Kirkwood | Rick Wise | Don Kirkwood | Rick Wise | | 559 | 693 | -134 |
| 1978-09-15 | @ BAL | 147 | L 3-8 | 57-90 | 7 | 4,000 | Jim Clancy | Jim Palmer | Jim Palmer | Victor Cruz | | 562 | 701 | -139 |
| 1978-09-16 | @ BAL | 148 | L 1-11 | 57-91 | 7 | 10,263 | Jesse Jefferson | Dennis Martinez | Dennis Martinez | Jesse Jefferson | | 563 | 712 | -149 |
| 1978-09-17 | @ BAL | 149 | L 0-5 | 57-92 | 7 | 4,436 | Don Kirkwood | Mike Flanagan | Mike Flanagan | Don Kirkwood | | 563 | 717 | -154 |
| 1978-09-20 | vs NYA | 150 | W 8-1 | 58-93 | 7 | 0 | Mike Willis | Ron Guidry | Mike Willis | Ron Guidry | | 571 | 718 | -147 |
| 1978-09-20 | vs NYA | 151 | L 2-3 | 58-93 | 7 | 38,080 | Tom Underwood | Ken Clay | Rich Gossage | Victor Cruz | | 573 | 721 | -148 |
| 1978-09-21 | vs NYA | 152 | L 1-7 | 58-94 | 7 | 28,653 | Balor Moore | Catfish Hunter | Catfish Hunter | Balor Moore | Rich Gossage | 574 | 728 | -154 |
| 1978-09-22 | vs BOS | 153 | W 5-4 | 59-94 | 7 | 22,172 | Jim Clancy | Bob Stanley | Tom Murphy | Andy Hassler | | 579 | 732 | -153 |
| 1978-09-23 | vs BOS | 154 | L 1-3 | 59-95 | 7 | 30,059 | Jesse Jefferson | Luis Tiant | Luis Tiant | Jesse Jefferson | | 580 | 735 | -155 |
| 1978-09-24 | vs BOS | 155 | L 6-7 | 59-96 | 7 | 33,618 | Don Kirkwood | Mike Torrez | Dick Drago | Tom Buskey | | 586 | 742 | -156 |
| 1978-09-26 | @ NYA | 156 | L 1-4 | 59-97 | 7 | 20,535 | Tom Underwood | Ed Figueroa | Ed Figueroa | Tom Underwood | Rich Gossage | 587 | 746 | -159 |
| 1978-09-27 | @ NYA | 157 | L 1-5 | 59-98 | 7 | 20,052 | Mike Willis | Catfish Hunter | Catfish Hunter | Mike Willis | | 588 | 751 | -163 |
| 1978-09-28 | @ NYA | 158 | L 1-3 | 59-99 | 7 | 30,480 | Balor Moore | Ron Guidry | Ron Guidry | Balor Moore | | 589 | 754 | -165 |
| 1978-09-29 | @ BOS | 159 | L 0-11 | 59-100 | 7 | 29,626 | Jim Clancy | Bob Stanley | Bob Stanley | Jim Clancy | | 589 | 765 | -176 |
| 1978-09-30 | @ BOS | 160 | L 1-5 | 59-101 | 7 | 32,659 | Jesse Jefferson | Dennis Eckersley | Dennis Eckersley | Jesse Jefferson | | 590 | 770 | -180 |
| 1978-10-01 | @ BOS | 161 | L 0-5 | 59-102 | 7 | 29,201 | Don Kirkwood | Luis Tiant | Luis Tiant | Don Kirkwood | | 590 | 775 | -185 |