| 1978-04-08 | vs KCA | 1 | W 8-5 | 1-0 | 1 | 52,433 | Wayne Garland | Dennis Leonard | Wayne Garland | Dennis Leonard | Mike Paxton | 8 | 5 | 3 |
| 1978-04-09 | vs KCA | 2 | L 4-5 | 1-1 | 3 | 7,473 | Rick Wise | Steve Busby | Steve Busby | Rick Wise | Steve Mingori | 12 | 10 | 2 |
| 1978-04-10 | vs BOS | 3 | W 5-4 | 2-1 | 2 | 4,177 | Don Hood | Allen Ripley | Jim Kern | Reggie Cleveland | | 17 | 14 | 3 |
| 1978-04-12 | vs BOS | 4 | L 3-6 | 2-2 | 3 | 6,234 | Wayne Garland | Mike Torrez | Mike Torrez | Wayne Garland | Dick Drago | 20 | 20 | 0 |
| 1978-04-14 | @ KCA | 5 | L 1-3 | 2-3 | 4 | 17,526 | Rick Wise | Paul Splittorff | Paul Splittorff | Rick Wise | Doug Bird | 21 | 23 | -2 |
| 1978-04-15 | @ KCA | 6 | L 5-6 | 2-4 | 5 | 18,110 | Don Hood | Steve Busby | Marty Pattin | Mike Paxton | Al Hrabosky | 26 | 29 | -3 |
| 1978-04-16 | @ KCA | 7 | L 1-2 | 2-5 | 6 | 17,655 | Wayne Garland | Dennis Leonard | Dennis Leonard | Wayne Garland | | 27 | 31 | -4 |
| 1978-04-17 | vs TEX | 8 | W 6-0 | 3-5 | 6 | 3,713 | Rick Waits | Jon Matlack | Rick Waits | Jon Matlack | | 33 | 31 | 2 |
| 1978-04-21 | @ BOS | 9 | L 7-9 | 3-6 | 6 | 25,401 | Wayne Garland | Mike Torrez | Dick Drago | Jim Kern | | 40 | 40 | 0 |
| 1978-04-22 | @ BOS | 10 | W 13-4 | 4-6 | 5 | 36,005 | Rick Wise | Allen Ripley | Rick Wise | Allen Ripley | | 53 | 44 | 9 |
| 1978-04-23 | @ BOS | 11 | L 3-6 | 5-7 | 5 | 0 | Rick Waits | Luis Tiant | Bill Campbell | Dennis Kinney | | 56 | 50 | 6 |
| 1978-04-23 | @ BOS | 12 | W 10-7 | 5-7 | 5 | 36,246 | Mike Paxton | Dennis Eckersley | Jim Kern | Bob Stanley | Dennis Kinney | 66 | 57 | 9 |
| 1978-04-24 | @ TOR | 13 | W 4-2 | 6-7 | 5 | 10,776 | Don Hood | Dave Lemanczyk | Don Hood | Dave Lemanczyk | Jim Kern | 70 | 59 | 11 |
| 1978-04-25 | @ TOR | 14 | W 6-5 | 7-7 | 3 | 11,348 | Wayne Garland | Jerry Garvin | Wayne Garland | Jerry Garvin | Dennis Kinney | 76 | 64 | 12 |
| 1978-04-26 | @ TEX | 15 | L 0-3 | 7-8 | 5 | 9,915 | Rick Wise | Doyle Alexander | Doyle Alexander | Rick Wise | | 76 | 67 | 9 |
| 1978-04-27 | @ TEX | 16 | L 1-3 | 7-9 | 5 | 11,133 | Rick Waits | Jon Matlack | Jon Matlack | Rick Waits | Len Barker | 77 | 70 | 7 |
| 1978-04-28 | @ OAK | 17 | W 6-2 | 8-9 | 5 | 5,513 | Don Hood | John Henry Johnson | Don Hood | John Henry Johnson | | 83 | 72 | 11 |
| 1978-04-29 | @ OAK | 18 | L 1-5 | 8-10 | 5 | 5,692 | Wayne Garland | Pete Broberg | Pete Broberg | Wayne Garland | Bob Lacey | 84 | 77 | 7 |
| 1978-04-30 | @ OAK | 19 | L 1-2 | 8-11 | 6 | 6,378 | Rick Wise | Rick Langford | Elias Sosa | Rick Wise | | 85 | 79 | 6 |
| 1978-05-02 | @ SEA | 20 | W 4-1 | 9-11 | 4 | 5,552 | Rick Waits | Dick Pole | Rick Waits | Dick Pole | Jim Kern | 89 | 80 | 9 |
| 1978-05-03 | @ SEA | 21 | W 10-5 | 10-11 | 4 | 5,321 | Don Hood | Byron McLaughlin | Don Hood | Byron McLaughlin | Dennis Kinney | 99 | 85 | 14 |
| 1978-05-05 | @ CAL | 22 | L 0-5 | 10-12 | 5 | 17,437 | Rick Wise | Nolan Ryan | Nolan Ryan | Rick Wise | | 99 | 90 | 9 |
| 1978-05-06 | @ CAL | 23 | L 3-7 | 10-13 | 5 | 40,750 | Mike Paxton | Chris Knapp | Chris Knapp | Mike Paxton | | 102 | 97 | 5 |
| 1978-05-07 | @ CAL | 24 | L 3-16 | 10-14 | 5 | 16,883 | Rick Waits | Don Aase | Don Aase | Rick Waits | Paul Hartzell | 105 | 113 | -8 |
| 1978-05-09 | vs SEA | 25 | W 5-4 | 11-14 | 5 | 3,515 | Don Hood | Byron McLaughlin | Jim Kern | Shane Rawley | | 110 | 117 | -7 |
| 1978-05-10 | vs SEA | 26 | W 6-1 | 12-14 | 4 | 3,202 | Rick Wise | Rick Honeycutt | Rick Wise | Rick Honeycutt | Dennis Kinney | 116 | 118 | -2 |
| 1978-05-12 | vs CAL | 27 | W 4-3 | 13-14 | 4 | 6,401 | Mike Paxton | Nolan Ryan | Mike Paxton | Nolan Ryan | Jim Kern | 120 | 121 | -1 |
| 1978-05-13 | vs CAL | 28 | W 2-1 | 14-14 | 4 | 13,811 | Rick Waits | Chris Knapp | Rick Waits | Chris Knapp | | 122 | 122 | 0 |
| 1978-05-14 | vs CAL | 29 | L 3-4 | 14-15 | 4 | 5,153 | Don Hood | Frank Tanana | Frank Tanana | Don Hood | Paul Hartzell | 125 | 126 | -1 |
| 1978-05-15 | vs OAK | 30 | L 2-3 | 14-16 | 4 | 3,454 | Rick Wise | Alan Wirth | Joe Coleman | Rick Wise | Elias Sosa | 127 | 129 | -2 |
| 1978-05-16 | vs OAK | 31 | W 3-2 | 15-16 | 4 | 3,737 | David Clyde | Steve Renko | David Clyde | Bob Lacey | | 130 | 131 | -1 |
| 1978-05-17 | vs NYA | 32 | W 5-4 | 16-16 | 4 | 10,370 | Rick Waits | Ed Figueroa | Sid Monge | Sparky Lyle | | 135 | 135 | 0 |
| 1978-05-18 | vs NYA | 33 | L 3-5 | 16-17 | 4 | 13,625 | Don Hood | Ron Guidry | Ron Guidry | Dennis Kinney | Rich Gossage | 138 | 140 | -2 |
| 1978-05-19 | vs BAL | 34 | W 7-5 | 17-17 | 4 | 15,565 | Mike Paxton | Dennis Martinez | Jim Kern | Don Stanhouse | | 145 | 145 | 0 |
| 1978-05-20 | vs BAL | 35 | L 1-2 | 17-18 | 4 | 11,426 | Rick Wise | Jim Palmer | Jim Palmer | Rick Wise | Don Stanhouse | 146 | 147 | -1 |
| 1978-05-21 | vs BAL | 36 | L 0-3 | 18-19 | 4 | 0 | Rick Waits | Scott McGregor | Scott McGregor | Rick Waits | | 146 | 150 | -4 |
| 1978-05-21 | vs BAL | 37 | W 3-2 | 18-19 | 4 | 23,206 | David Clyde | Nelson Briles | David Clyde | Nelson Briles | Dennis Kinney | 149 | 152 | -3 |
| 1978-05-23 | @ NYA | 38 | L 1-10 | 18-20 | 5 | 20,618 | Don Hood | Ron Guidry | Ron Guidry | Don Hood | | 150 | 162 | -12 |
| 1978-05-25 | @ NYA | 39 | L 3-9 | 18-21 | 6 | 15,403 | Rick Waits | Dick Tidrow | Dick Tidrow | Rick Waits | | 153 | 171 | -18 |
| 1978-05-26 | @ BAL | 40 | L 3-4 | 18-22 | 6 | 29,215 | Rick Wise | Nelson Briles | Tippy Martinez | Rick Wise | | 156 | 175 | -19 |
| 1978-05-27 | @ BAL | 41 | W 6-2 | 19-22 | 6 | 8,920 | David Clyde | Mike Flanagan | David Clyde | Mike Flanagan | | 162 | 177 | -15 |
| 1978-05-28 | @ BAL | 42 | W 4-3 | 20-23 | 6 | 0 | Don Hood | Dennis Martinez | Sid Monge | Don Stanhouse | | 166 | 180 | -14 |
| 1978-05-28 | @ BAL | 43 | L 0-3 | 20-23 | 6 | 18,276 | Mike Paxton | Jim Palmer | Jim Palmer | Mike Paxton | | 166 | 183 | -17 |
| 1978-05-29 | vs NYA | 44 | L 0-2 | 20-24 | 6 | 19,563 | Rick Waits | Andy Messersmith | Rawly Eastwick | Rick Waits | | 166 | 185 | -19 |
| 1978-05-30 | vs NYA | 45 | W 5-1 | 21-24 | 6 | 6,069 | Rick Wise | Dick Tidrow | Rick Wise | Dick Tidrow | | 171 | 186 | -15 |
| 1978-06-02 | @ MIL | 46 | W 7-6 | 22-24 | 6 | 16,779 | David Clyde | Andy Replogle | Jim Kern | Bob McClure | | 178 | 192 | -14 |
| 1978-06-03 | @ MIL | 47 | W 6-4 | 23-24 | 5 | 11,933 | Mike Paxton | Jerry Augustine | Mike Paxton | Jerry Augustine | Sid Monge | 184 | 196 | -12 |
| 1978-06-04 | @ MIL | 48 | L 7-12 | 23-26 | 6 | 0 | Rick Wise | Mike Caldwell | Randy Stein | Rick Wise | | 191 | 208 | -17 |
| 1978-06-04 | @ MIL | 49 | L 4-9 | 23-26 | 6 | 23,850 | Don Hood | Bill Travers | Bill Travers | Don Hood | Bill Castro | 195 | 217 | -22 |
| 1978-06-05 | vs CHA | 50 | L 0-2 | 23-27 | 6 | 5,391 | Rick Waits | Steve Stone | Steve Stone | Rick Waits | | 195 | 219 | -24 |
| 1978-06-06 | vs CHA | 51 | L 0-3 | 23-28 | 6 | 4,417 | Sid Monge | Francisco Barrios | Francisco Barrios | Sid Monge | | 195 | 222 | -27 |
| 1978-06-09 | vs MIN | 52 | W 7-3 | 24-28 | 6 | 8,390 | David Clyde | Geoff Zahn | David Clyde | Geoff Zahn | Jim Kern | 202 | 225 | -23 |
| 1978-06-10 | vs MIN | 53 | W 4-3 | 25-28 | 6 | 16,048 | Rick Wise | Roger Erickson | Rick Wise | Mike Marshall | Jim Kern | 206 | 228 | -22 |
| 1978-06-11 | vs MIN | 54 | W 2-1 | 26-28 | 6 | 25,547 | Don Hood | Gary Serum | Mike Paxton | Mike Marshall | | 208 | 229 | -21 |
| 1978-06-12 | @ CHA | 55 | L 0-1 | 26-29 | 6 | 17,373 | Rick Waits | Ken Kravec | Ken Kravec | Rick Waits | Jim Willoughby | 208 | 230 | -22 |
| 1978-06-13 | @ CHA | 56 | L 9-10 | 26-30 | 6 | 12,000 | Sid Monge | Wilbur Wood | Rich Hinton | Al Fitzmorris | Lerrin LaGrow | 217 | 240 | -23 |
| 1978-06-14 | @ MIN | 57 | L 2-8 | 26-31 | 6 | 6,612 | David Clyde | Roger Erickson | Roger Erickson | David Clyde | | 219 | 248 | -29 |
| 1978-06-16 | vs MIL | 58 | L 6-8 | 26-32 | 6 | 9,175 | Rick Wise | Lary Sorensen | Bob McClure | Jim Kern | Bill Castro | 225 | 256 | -31 |
| 1978-06-17 | vs MIL | 59 | L 3-4 | 26-33 | 6 | 16,923 | Don Hood | Andy Replogle | Bill Castro | Jim Kern | | 228 | 260 | -32 |
| 1978-06-18 | vs MIL | 60 | W 3-0 | 27-34 | 6 | 0 | Rick Waits | Mike Caldwell | Rick Waits | Mike Caldwell | | 231 | 260 | -29 |
| 1978-06-18 | vs MIL | 61 | L 1-4 | 27-34 | 6 | 20,140 | Mike Paxton | Jerry Augustine | Jerry Augustine | Mike Paxton | Bill Castro | 232 | 264 | -32 |
| 1978-06-19 | @ KCA | 62 | L 5-6 | 27-35 | 6 | 25,660 | David Clyde | Dennis Leonard | Dennis Leonard | David Clyde | Al Hrabosky | 237 | 270 | -33 |
| 1978-06-20 | @ KCA | 63 | L 2-3 | 27-36 | 6 | 20,444 | Rick Wise | Larry Gura | Larry Gura | Rick Wise | | 239 | 273 | -34 |
| 1978-06-21 | @ KCA | 64 | W 4-2 | 28-36 | 6 | 23,818 | Don Hood | Rich Gale | Dan Spillner | Doug Bird | Jim Kern | 243 | 275 | -32 |
| 1978-06-23 | vs TOR | 65 | W 8-3 | 29-36 | 6 | 6,514 | Rick Waits | Jesse Jefferson | Rick Waits | Jesse Jefferson | | 251 | 278 | -27 |
| 1978-06-24 | vs TOR | 66 | W 12-3 | 30-36 | 6 | 7,176 | Mike Paxton | Jim Clancy | Mike Paxton | Jim Clancy | | 263 | 281 | -18 |
| 1978-06-25 | vs TOR | 67 | L 1-2 | 31-37 | 6 | 0 | David Clyde | Balor Moore | Balor Moore | David Clyde | Victor Cruz | 264 | 283 | -19 |
| 1978-06-25 | vs TOR | 68 | W 3-2 | 31-37 | 6 | 21,959 | Rick Wise | Jerry Garvin | Rick Wise | Jerry Garvin | Sid Monge | 267 | 285 | -18 |
| 1978-06-26 | vs DET | 69 | W 5-4 | 32-37 | 6 | 4,633 | Don Hood | Jack Billingham | Don Hood | Jack Billingham | Dan Spillner | 272 | 289 | -17 |
| 1978-06-27 | vs DET | 70 | L 1-6 | 32-38 | 6 | 12,214 | Dave Freisleben | Dave Rozema | Dave Rozema | Dave Freisleben | | 273 | 295 | -22 |
| 1978-06-28 | vs DET | 71 | L 3-4 | 33-39 | 6 | 0 | Rick Waits | Jim Slaton | Jim Slaton | Rick Waits | John Hiller | 276 | 299 | -23 |
| 1978-06-28 | vs DET | 72 | W 2-1 | 33-39 | 6 | 13,489 | Mike Paxton | Milt Wilcox | Mike Paxton | Milt Wilcox | Sid Monge | 278 | 300 | -22 |
| 1978-06-29 | vs DET | 73 | W 6-3 | 34-39 | 6 | 5,672 | David Clyde | Bob Sykes | Jim Kern | Jack Morris | | 284 | 303 | -19 |
| 1978-06-30 | @ TOR | 74 | W 3-0 | 35-39 | 6 | 16,129 | Rick Wise | Jerry Garvin | Rick Wise | Jerry Garvin | | 287 | 303 | -16 |
| 1978-07-01 | @ TOR | 75 | L 3-9 | 35-40 | 6 | 19,277 | Don Hood | Tom Underwood | Tom Underwood | Don Hood | Victor Cruz | 290 | 312 | -22 |
| 1978-07-02 | @ TOR | 76 | W 2-0 | 36-41 | 6 | 0 | Rick Waits | Dave Lemanczyk | Rick Waits | Dave Lemanczyk | Jim Kern | 292 | 312 | -20 |
| 1978-07-02 | @ TOR | 77 | L 1-3 | 36-41 | 6 | 28,305 | Dave Freisleben | Jesse Jefferson | Jesse Jefferson | Dave Freisleben | | 293 | 315 | -22 |
| 1978-07-03 | vs BAL | 78 | W 9-0 | 37-41 | 6 | 9,302 | Mike Paxton | Scott McGregor | Mike Paxton | Scott McGregor | | 302 | 315 | -13 |
| 1978-07-04 | vs BAL | 79 | L 4-6 | 37-42 | 6 | 36,300 | David Clyde | Dennis Martinez | Dennis Martinez | David Clyde | Don Stanhouse | 306 | 321 | -15 |
| 1978-07-05 | @ DET | 80 | L 3-13 | 37-43 | 6 | 12,778 | Rick Wise | Jack Billingham | Jack Billingham | Rick Wise | | 309 | 334 | -25 |
| 1978-07-06 | @ DET | 81 | L 4-8 | 37-44 | 6 | 17,125 | Rick Waits | Jim Slaton | Bob Sykes | Rick Waits | John Hiller | 313 | 342 | -29 |
| 1978-07-07 | vs BOS | 82 | W 10-9 | 38-44 | 6 | 19,543 | Dave Freisleben | Mike Torrez | Dan Spillner | Bill Campbell | | 323 | 351 | -28 |
| 1978-07-08 | vs BOS | 83 | L 5-12 | 38-46 | 6 | 0 | Mike Paxton | Dennis Eckersley | Dennis Eckersley | Mike Paxton | | 328 | 363 | -35 |
| 1978-07-08 | vs BOS | 84 | L 2-3 | 38-46 | 6 | 41,859 | David Clyde | Jim Wright | Jim Wright | David Clyde | Bob Stanley | 330 | 366 | -36 |
| 1978-07-09 | vs BOS | 85 | W 7-1 | 39-46 | 6 | 41,394 | Rick Wise | Allen Ripley | Rick Wise | Allen Ripley | | 337 | 367 | -30 |
| 1978-07-13 | @ OAK | 86 | L 3-7 | 39-47 | 6 | 2,987 | Rick Waits | John Henry Johnson | John Henry Johnson | Rick Waits | Dave Heaverlo | 340 | 374 | -34 |
| 1978-07-14 | @ OAK | 87 | W 11-1 | 40-47 | 6 | 3,326 | Rick Wise | Matt Keough | Rick Wise | Matt Keough | | 351 | 375 | -24 |
| 1978-07-15 | @ SEA | 88 | L 6-7 | 40-48 | 6 | 26,117 | Mike Paxton | Mike Parrott | Enrique Romo | Mike Paxton | | 357 | 382 | -25 |
| 1978-07-16 | @ SEA | 89 | W 8-4 | 41-48 | 6 | 8,312 | David Clyde | Paul Mitchell | David Clyde | Paul Mitchell | Sid Monge | 365 | 386 | -21 |
| 1978-07-17 | @ SEA | 90 | W 5-2 | 42-48 | 6 | 7,676 | Dave Freisleben | Jim Colborn | Dave Freisleben | Jim Colborn | Sid Monge | 370 | 388 | -18 |
| 1978-07-18 | @ CAL | 91 | W 8-3 | 43-48 | 6 | 16,726 | Rick Waits | Don Aase | Rick Waits | Don Aase | Jim Kern | 378 | 391 | -13 |
| 1978-07-19 | @ CAL | 92 | L 0-3 | 43-49 | 6 | 18,584 | Rick Wise | Nolan Ryan | Nolan Ryan | Rick Wise | | 378 | 394 | -16 |
| 1978-07-21 | vs SEA | 93 | W 11-0 | 44-49 | 6 | 13,908 | Mike Paxton | Mike Parrott | Mike Paxton | Mike Parrott | | 389 | 394 | -5 |
| 1978-07-22 | vs SEA | 94 | W 8-5 | 45-49 | 6 | 10,279 | David Clyde | Paul Mitchell | Paul Reuschel | Paul Mitchell | | 397 | 399 | -2 |
| 1978-07-24 | vs CAL | 95 | L 4-5 | 45-50 | 6 | 8,798 | Rick Wise | Paul Hartzell | Tom Griffin | Jim Kern | | 401 | 404 | -3 |
| 1978-07-25 | vs CAL | 96 | W 5-1 | 46-50 | 6 | 6,781 | Mike Paxton | Dave Frost | Mike Paxton | Dave Frost | Dan Spillner | 406 | 405 | 1 |
| 1978-07-26 | @ NYA | 97 | L 1-3 | 46-51 | 6 | 31,631 | Rick Waits | Jim Beattie | Rich Gossage | Rick Waits | | 407 | 408 | -1 |
| 1978-07-27 | @ NYA | 98 | L 0-11 | 47-52 | 6 | 0 | David Clyde | Ed Figueroa | Ed Figueroa | David Clyde | | 407 | 419 | -12 |
| 1978-07-27 | @ NYA | 99 | W 17-5 | 47-52 | 6 | 33,412 | Don Hood | Catfish Hunter | Don Hood | Catfish Hunter | | 424 | 424 | 0 |
| 1978-07-28 | vs OAK | 100 | W 4-2 | 48-52 | 6 | 8,032 | Dave Freisleben | Pete Broberg | Jim Kern | Pete Broberg | | 428 | 426 | 2 |
| 1978-07-29 | vs OAK | 101 | L 5-6 | 48-53 | 6 | 17,828 | Rick Wise | Steve Renko | Steve Renko | Rick Wise | Dave Heaverlo | 433 | 432 | 1 |
| 1978-07-30 | vs OAK | 102 | L 4-5 | 48-54 | 6 | 10,272 | Mike Paxton | John Henry Johnson | Elias Sosa | Jim Kern | | 437 | 437 | 0 |
| 1978-07-31 | vs KCA | 103 | W 4-3 | 49-54 | 6 | 8,149 | Rick Waits | Larry Gura | Sid Monge | Al Hrabosky | | 441 | 440 | 1 |
| 1978-08-01 | vs KCA | 104 | W 2-1 | 50-54 | 6 | 8,236 | David Clyde | Rich Gale | Jim Kern | Steve Mingori | | 443 | 441 | 2 |
| 1978-08-02 | vs KCA | 105 | W 5-2 | 51-54 | 6 | 7,834 | Dave Freisleben | Dennis Leonard | Paul Reuschel | Dennis Leonard | | 448 | 443 | 5 |
| 1978-08-04 | @ TEX | 106 | L 0-8 | 51-55 | 6 | 20,307 | Rick Wise | Fergie Jenkins | Fergie Jenkins | Rick Wise | | 448 | 451 | -3 |
| 1978-08-05 | @ TEX | 107 | L 3-4 | 51-56 | 6 | 15,376 | Mike Paxton | Doyle Alexander | Steve Comer | Jim Kern | | 451 | 455 | -4 |
| 1978-08-06 | @ TEX | 108 | L 2-3 | 51-57 | 6 | 15,004 | Rick Waits | Jon Matlack | Jon Matlack | Rick Waits | | 453 | 458 | -5 |
| 1978-08-08 | @ BOS | 109 | L 7-9 | 51-58 | 6 | 34,485 | Dave Freisleben | Mike Torrez | Bob Stanley | Dave Freisleben | | 460 | 467 | -7 |
| 1978-08-09 | @ BOS | 110 | W 5-1 | 52-58 | 6 | 33,285 | Rick Wise | Bill Lee | Rick Wise | Bill Lee | Jim Kern | 465 | 468 | -3 |
| 1978-08-10 | @ BOS | 111 | L 5-6 | 52-59 | 6 | 33,541 | Mike Paxton | Dennis Eckersley | Bob Stanley | Dan Spillner | | 470 | 474 | -4 |
| 1978-08-11 | vs TEX | 112 | L 2-8 | 52-60 | 6 | 19,085 | Rick Waits | Jon Matlack | Jon Matlack | Rick Waits | | 472 | 482 | -10 |
| 1978-08-12 | vs TEX | 113 | L 1-6 | 52-61 | 6 | 13,783 | David Clyde | Doyle Alexander | Doyle Alexander | David Clyde | | 473 | 488 | -15 |
| 1978-08-13 | vs TEX | 114 | L 2-3 | 52-63 | 6 | 0 | Dave Freisleben | Doc Medich | Doc Medich | Dave Freisleben | Reggie Cleveland | 475 | 491 | -16 |
| 1978-08-13 | vs TEX | 115 | L 5-6 | 52-63 | 6 | 14,137 | Rick Wise | Paul Mirabella | Steve Comer | Rick Wise | Len Barker | 480 | 497 | -17 |
| 1978-08-14 | vs MIN | 116 | W 4-3 | 53-63 | 6 | 6,513 | Mike Paxton | Jeff Holly | Mike Paxton | Jeff Holly | Jim Kern | 484 | 500 | -16 |
| 1978-08-15 | vs MIN | 117 | L 8-9 | 53-64 | 6 | 6,971 | Rick Waits | Darrell Jackson | Mike Marshall | Sid Monge | Gary Serum | 492 | 509 | -17 |
| 1978-08-16 | @ DET | 118 | L 0-2 | 53-65 | 6 | 15,819 | David Clyde | Jack Billingham | Jack Billingham | David Clyde | | 492 | 511 | -19 |
| 1978-08-17 | @ DET | 119 | L 5-9 | 53-66 | 6 | 18,966 | Dave Freisleben | Jim Slaton | Jack Morris | Don Hood | | 497 | 520 | -23 |
| 1978-08-18 | vs CHA | 120 | L 1-7 | 53-67 | 6 | 6,972 | Rick Wise | Mike Proly | Mike Proly | Rick Wise | | 498 | 527 | -29 |
| 1978-08-19 | vs CHA | 121 | L 1-2 | 53-68 | 6 | 5,282 | Mike Paxton | Francisco Barrios | Francisco Barrios | Mike Paxton | | 499 | 529 | -30 |
| 1978-08-20 | vs CHA | 122 | W 10-1 | 54-68 | 6 | 8,233 | Rick Waits | Steve Stone | Rick Waits | Steve Stone | | 509 | 530 | -21 |
| 1978-08-22 | @ MIL | 123 | L 2-3 | 54-70 | 6 | 0 | David Clyde | Bill Travers | Bill Castro | Jim Kern | | 511 | 533 | -22 |
| 1978-08-22 | @ MIL | 124 | L 4-5 | 54-70 | 6 | 23,918 | Paul Reuschel | Eduardo Rodriguez | Willie Mueller | Jim Kern | | 515 | 538 | -23 |
| 1978-08-23 | @ MIL | 125 | L 4-9 | 54-71 | 6 | 20,157 | Rick Wise | Lary Sorensen | Andy Replogle | Sid Monge | | 519 | 547 | -28 |
| 1978-08-24 | @ MIL | 126 | W 9-8 | 55-71 | 6 | 16,362 | Mike Paxton | Jerry Augustine | Dan Spillner | Bob McClure | Sid Monge | 528 | 555 | -27 |
| 1978-08-25 | @ CHA | 127 | W 2-1 | 56-71 | 6 | 18,891 | Rick Waits | Francisco Barrios | Rick Waits | Francisco Barrios | Jim Kern | 530 | 556 | -26 |
| 1978-08-26 | @ CHA | 128 | L 7-8 | 56-72 | 6 | 19,100 | David Clyde | Steve Stone | Steve Stone | David Clyde | Jim Willoughby | 537 | 564 | -27 |
| 1978-08-27 | @ CHA | 129 | L 0-6 | 56-73 | 6 | 13,008 | Paul Reuschel | Ross Baumgarten | Ross Baumgarten | Paul Reuschel | | 537 | 570 | -33 |
| 1978-08-29 | vs MIL | 130 | L 0-6 | 56-74 | 6 | 5,498 | Rick Wise | Andy Replogle | Andy Replogle | Rick Wise | | 537 | 576 | -39 |
| 1978-08-31 | vs MIL | 131 | L 0-1 | 57-75 | 6 | 0 | Mike Paxton | Mike Caldwell | Mike Caldwell | Mike Paxton | | 537 | 577 | -40 |
| 1978-08-31 | vs MIL | 132 | W 12-6 | 57-75 | 6 | 5,328 | Rick Waits | Bill Travers | Rick Waits | Bill Travers | | 549 | 583 | -34 |
| 1978-09-01 | @ MIN | 133 | W 4-1 | 58-75 | 6 | 4,917 | David Clyde | Roger Erickson | David Clyde | Roger Erickson | Dan Spillner | 553 | 584 | -31 |
| 1978-09-02 | @ MIN | 134 | L 1-2 | 58-76 | 6 | 6,775 | Paul Reuschel | Dave Goltz | Dave Goltz | Paul Reuschel | Mike Marshall | 554 | 586 | -32 |
| 1978-09-03 | @ MIN | 135 | L 3-12 | 58-78 | 6 | 0 | Rick Wise | Gary Serum | Gary Serum | Rick Wise | | 557 | 598 | -41 |
| 1978-09-03 | @ MIN | 136 | L 3-4 | 58-78 | 6 | 10,240 | Dave Freisleben | Stan Perzanowski | Mike Marshall | Jim Kern | | 560 | 602 | -42 |
| 1978-09-04 | @ TOR | 137 | W 5-4 | 59-78 | 6 | 14,364 | Mike Paxton | Balor Moore | Mike Paxton | Balor Moore | | 565 | 606 | -41 |
| 1978-09-05 | @ TOR | 138 | W 6-2 | 60-78 | 6 | 11,060 | Rick Waits | Don Kirkwood | Rick Waits | Don Kirkwood | | 571 | 608 | -37 |
| 1978-09-08 | @ DET | 139 | L 3-6 | 60-79 | 6 | 13,624 | David Clyde | Jim Slaton | Jim Slaton | David Clyde | John Hiller | 574 | 614 | -40 |
| 1978-09-09 | @ DET | 140 | L 2-5 | 60-80 | 6 | 16,026 | Mike Paxton | Dave Rozema | Dave Rozema | Mike Paxton | | 576 | 619 | -43 |
| 1978-09-10 | @ DET | 141 | W 7-4 | 61-80 | 6 | 15,583 | Paul Reuschel | Milt Wilcox | Jim Kern | Milt Wilcox | | 583 | 623 | -40 |
| 1978-09-11 | vs TOR | 142 | W 6-4 | 62-81 | 6 | 0 | Rick Waits | Jesse Jefferson | Rick Waits | Jesse Jefferson | | 589 | 627 | -38 |
| 1978-09-11 | vs TOR | 143 | L 1-7 | 62-81 | 6 | 3,356 | Rick Wise | Don Kirkwood | Don Kirkwood | Rick Wise | | 590 | 634 | -44 |
| 1978-09-13 | vs BOS | 144 | W 2-1 | 63-81 | 6 | 5,568 | David Clyde | Dennis Eckersley | David Clyde | Dennis Eckersley | Jim Kern | 592 | 635 | -43 |
| 1978-09-14 | vs BOS | 145 | W 4-3 | 64-81 | 6 | 4,479 | Mike Paxton | Jim Wright | Mike Paxton | Jim Wright | Jim Kern | 596 | 638 | -42 |
| 1978-09-15 | vs DET | 146 | L 0-1 | 64-82 | 6 | 4,070 | Paul Reuschel | Dave Rozema | Dave Rozema | Paul Reuschel | | 596 | 639 | -43 |
| 1978-09-16 | vs DET | 147 | L 4-10 | 64-83 | 6 | 4,640 | Rick Waits | Milt Wilcox | Milt Wilcox | Rick Waits | | 600 | 649 | -49 |
| 1978-09-17 | vs DET | 148 | W 2-1 | 65-83 | 6 | 4,515 | Don Hood | Kip Young | Jim Kern | Kip Young | | 602 | 650 | -48 |
| 1978-09-18 | vs BAL | 149 | L 3-10 | 65-84 | 6 | 2,873 | David Clyde | Scott McGregor | Scott McGregor | David Clyde | | 605 | 660 | -55 |
| 1978-09-19 | vs BAL | 150 | W 2-1 | 66-84 | 6 | 3,148 | Mike Paxton | Jim Palmer | Mike Paxton | Don Stanhouse | | 607 | 661 | -54 |
| 1978-09-22 | vs NYA | 151 | W 8-7 | 67-84 | 6 | 10,035 | Rick Waits | Ed Figueroa | Sid Monge | Rich Gossage | | 615 | 668 | -53 |
| 1978-09-23 | vs NYA | 152 | W 10-1 | 68-84 | 6 | 17,452 | David Clyde | Jim Beattie | David Clyde | Jim Beattie | | 625 | 669 | -44 |
| 1978-09-24 | vs NYA | 153 | L 0-4 | 68-85 | 6 | 15,855 | Mike Paxton | Ron Guidry | Ron Guidry | Mike Paxton | | 625 | 673 | -48 |
| 1978-09-26 | @ BAL | 154 | L 1-3 | 68-86 | 6 | 3,662 | Paul Reuschel | Mike Flanagan | Mike Flanagan | Paul Reuschel | Don Stanhouse | 626 | 676 | -50 |
| 1978-09-27 | @ BAL | 155 | L 1-3 | 68-87 | 6 | 2,987 | Rick Waits | Dennis Martinez | Dennis Martinez | Rick Waits | | 627 | 679 | -52 |
| 1978-09-28 | @ BAL | 156 | L 2-3 | 68-88 | 6 | 5,143 | Don Hood | Jim Palmer | Jim Palmer | Don Hood | Don Stanhouse | 629 | 682 | -53 |
| 1978-09-29 | @ NYA | 157 | L 1-3 | 68-89 | 6 | 30,253 | David Clyde | Jim Beattie | Jim Beattie | Jim Kern | Rich Gossage | 630 | 685 | -55 |
| 1978-09-30 | @ NYA | 158 | L 0-7 | 68-90 | 6 | 55,219 | Mike Paxton | Ed Figueroa | Ed Figueroa | Mike Paxton | | 630 | 692 | -62 |
| 1978-10-01 | @ NYA | 159 | W 9-2 | 69-90 | 6 | 39,189 | Rick Waits | Catfish Hunter | Rick Waits | Catfish Hunter | | 639 | 694 | -55 |