| 1978-04-05 | vs MIN | 1 | W 3-2 | 1-0 | 1 | 45,235 | Glenn Abbott | Dave Goltz | Glenn Abbott | Dave Goltz | Enrique Romo | 3 | 2 | 1 |
| 1978-04-06 | vs MIN | 2 | L 4-5 | 1-1 | 2 | 10,311 | Dick Pole | Roger Erickson | Roger Erickson | Dick Pole | Tom Johnson | 7 | 7 | 0 |
| 1978-04-07 | vs MIN | 3 | W 6-3 | 2-1 | 3 | 11,530 | Rick Honeycutt | Pete Redfern | Rick Honeycutt | Pete Redfern | Enrique Romo | 13 | 10 | 3 |
| 1978-04-08 | vs MIN | 4 | L 2-8 | 2-2 | 5 | 12,896 | Paul Mitchell | Paul Thormodsgard | Paul Thormodsgard | Paul Mitchell | | 15 | 18 | -3 |
| 1978-04-09 | vs MIN | 5 | L 6-8 | 2-3 | 6 | 11,803 | Tom House | Geoff Zahn | Gary Serum | Tom House | | 21 | 26 | -5 |
| 1978-04-10 | @ OAK | 6 | L 0-1 | 2-4 | 7 | 17,283 | Glenn Abbott | John Henry Johnson | John Henry Johnson | Glenn Abbott | Dave Heaverlo | 21 | 27 | -6 |
| 1978-04-11 | @ OAK | 7 | L 0-2 | 2-5 | 7 | 1,890 | Dick Pole | Pete Broberg | Pete Broberg | Dick Pole | Elias Sosa | 21 | 29 | -8 |
| 1978-04-12 | @ OAK | 8 | L 3-4 | 2-6 | 7 | 1,742 | Rick Honeycutt | Rick Langford | Dave Heaverlo | Shane Rawley | | 24 | 33 | -9 |
| 1978-04-13 | @ OAK | 9 | L 1-3 | 2-7 | 7 | 2,034 | Paul Mitchell | Matt Keough | Bob Lacey | Steve Burke | | 25 | 36 | -11 |
| 1978-04-14 | @ MIN | 10 | L 5-14 | 2-8 | 7 | 17,425 | Tom House | Geoff Zahn | Geoff Zahn | Tom House | | 30 | 50 | -20 |
| 1978-04-15 | @ MIN | 11 | L 5-6 | 2-9 | 7 | 7,471 | Jim Todd | Dave Goltz | Tom Johnson | John Montague | | 35 | 56 | -21 |
| 1978-04-16 | @ MIN | 12 | W 8-5 | 4-9 | 6 | 0 | Dick Pole | Roger Erickson | Dick Pole | Roger Erickson | Shane Rawley | 43 | 61 | -18 |
| 1978-04-16 | @ MIN | 13 | W 7-2 | 4-9 | 6 | 14,021 | Tom House | Dave Johnson | Tom House | Dave Johnson | | 50 | 63 | -13 |
| 1978-04-17 | vs CAL | 14 | L 3-7 | 4-10 | 6 | 7,562 | Rick Honeycutt | Frank Tanana | Frank Tanana | Rick Honeycutt | | 53 | 70 | -17 |
| 1978-04-18 | vs CAL | 15 | W 6-1 | 5-10 | 6 | 6,679 | Paul Mitchell | Nolan Ryan | Paul Mitchell | Nolan Ryan | | 59 | 71 | -12 |
| 1978-04-19 | vs CAL | 16 | L 2-11 | 5-11 | 6 | 7,181 | Glenn Abbott | Chris Knapp | Chris Knapp | Jim Todd | Paul Hartzell | 61 | 82 | -21 |
| 1978-04-21 | vs OAK | 17 | L 3-5 | 5-12 | 6 | 7,939 | Dick Pole | Matt Keough | Matt Keough | Dick Pole | Elias Sosa | 64 | 87 | -23 |
| 1978-04-22 | vs OAK | 18 | L 0-3 | 5-13 | 6 | 23,756 | Rick Honeycutt | Alan Wirth | Alan Wirth | Rick Honeycutt | Elias Sosa | 64 | 90 | -26 |
| 1978-04-23 | vs OAK | 19 | L 0-5 | 5-14 | 6 | 5,688 | Paul Mitchell | John Henry Johnson | John Henry Johnson | Paul Mitchell | | 64 | 95 | -31 |
| 1978-04-24 | @ CAL | 20 | W 6-5 | 6-14 | 6 | 13,429 | Mike Parrott | Nolan Ryan | Enrique Romo | Paul Hartzell | Shane Rawley | 70 | 100 | -30 |
| 1978-04-25 | @ CAL | 21 | L 0-3 | 6-15 | 6 | 9,484 | Byron McLaughlin | Chris Knapp | Chris Knapp | Byron McLaughlin | Dave LaRoche | 70 | 103 | -33 |
| 1978-04-26 | @ CAL | 22 | W 5-4 | 7-15 | 6 | 11,868 | Dick Pole | Ken Brett | Dick Pole | Ken Brett | Shane Rawley | 75 | 107 | -32 |
| 1978-04-27 | @ CAL | 23 | L 1-5 | 7-16 | 7 | 13,609 | Jim Todd | Frank Tanana | Frank Tanana | Jim Todd | | 76 | 112 | -36 |
| 1978-04-28 | vs DET | 24 | L 4-5 | 7-17 | 7 | 10,240 | Rick Honeycutt | Jim Slaton | Jim Slaton | Rick Honeycutt | John Hiller | 80 | 117 | -37 |
| 1978-04-29 | vs DET | 25 | L 0-5 | 7-18 | 7 | 12,123 | Paul Mitchell | Dave Rozema | Dave Rozema | Paul Mitchell | | 80 | 122 | -42 |
| 1978-04-30 | vs DET | 26 | W 4-3 | 8-18 | 7 | 7,474 | Mike Parrott | Jack Billingham | Enrique Romo | Steve Foucault | | 84 | 125 | -41 |
| 1978-05-02 | vs CLE | 27 | L 1-4 | 8-19 | 7 | 5,552 | Dick Pole | Rick Waits | Rick Waits | Dick Pole | Jim Kern | 85 | 129 | -44 |
| 1978-05-03 | vs CLE | 28 | L 5-10 | 8-20 | 7 | 5,321 | Byron McLaughlin | Don Hood | Don Hood | Byron McLaughlin | Dennis Kinney | 90 | 139 | -49 |
| 1978-05-05 | vs TOR | 29 | W 9-1 | 9-20 | 6 | 4,824 | Rick Honeycutt | Jesse Jefferson | Rick Honeycutt | Jesse Jefferson | | 99 | 140 | -41 |
| 1978-05-06 | vs TOR | 30 | W 6-0 | 10-20 | 5 | 7,589 | Paul Mitchell | Dave Lemanczyk | Paul Mitchell | Dave Lemanczyk | | 105 | 140 | -35 |
| 1978-05-07 | vs TOR | 31 | W 9-7 | 11-20 | 5 | 12,489 | Dick Pole | Jerry Garvin | Enrique Romo | Mike Willis | | 114 | 147 | -33 |
| 1978-05-09 | @ CLE | 32 | L 4-5 | 11-21 | 5 | 3,515 | Byron McLaughlin | Don Hood | Jim Kern | Shane Rawley | | 118 | 152 | -34 |
| 1978-05-10 | @ CLE | 33 | L 1-6 | 11-22 | 6 | 3,202 | Rick Honeycutt | Rick Wise | Rick Wise | Rick Honeycutt | Dennis Kinney | 119 | 158 | -39 |
| 1978-05-12 | @ TOR | 34 | L 3-8 | 11-23 | 6 | 11,518 | Paul Mitchell | Jesse Jefferson | Jesse Jefferson | Shane Rawley | | 122 | 166 | -44 |
| 1978-05-13 | @ TOR | 35 | W 9-6 | 12-23 | 6 | 21,350 | Dick Pole | Dave Lemanczyk | Dick Pole | Dave Lemanczyk | Enrique Romo | 131 | 172 | -41 |
| 1978-05-15 | @ DET | 36 | L 2-4 | 12-24 | 5 | 8,412 | Glenn Abbott | Jim Slaton | Jim Slaton | Glenn Abbott | | 133 | 176 | -43 |
| 1978-05-16 | @ DET | 37 | L 2-4 | 12-25 | 6 | 12,423 | Rick Honeycutt | Milt Wilcox | Steve Foucault | Shane Rawley | | 135 | 180 | -45 |
| 1978-05-19 | vs TEX | 38 | W 6-5 | 13-26 | 7 | 0 | Dick Pole | Dock Ellis | Tom House | Steve Comer | | 141 | 185 | -44 |
| 1978-05-19 | vs TEX | 39 | L 2-4 | 13-26 | 7 | 8,933 | Paul Mitchell | Doc Medich | Doc Medich | Paul Mitchell | Paul Lindblad | 143 | 189 | -46 |
| 1978-05-20 | vs TEX | 40 | W 7-3 | 14-26 | 6 | 34,835 | Glenn Abbott | Fergie Jenkins | Shane Rawley | Fergie Jenkins | Enrique Romo | 150 | 192 | -42 |
| 1978-05-21 | vs TEX | 41 | L 4-5 | 14-27 | 7 | 28,689 | Byron McLaughlin | Doyle Alexander | Doyle Alexander | Enrique Romo | Reggie Cleveland | 154 | 197 | -43 |
| 1978-05-22 | vs KCA | 42 | W 10-1 | 15-27 | 6 | 6,190 | Tom House | Dennis Leonard | Tom House | Dennis Leonard | | 164 | 198 | -34 |
| 1978-05-23 | vs KCA | 43 | W 4-3 | 16-28 | 6 | 0 | Dick Pole | Andy Hassler | Dick Pole | Andy Hassler | Jim Todd | 168 | 201 | -33 |
| 1978-05-23 | vs KCA | 44 | L 3-5 | 16-28 | 6 | 8,275 | Shane Rawley | Larry Gura | Doug Bird | Shane Rawley | Al Hrabosky | 171 | 206 | -35 |
| 1978-05-24 | vs KCA | 45 | L 5-6 | 16-29 | 6 | 6,717 | Paul Mitchell | Rich Gale | Steve Mingori | Jim Todd | Al Hrabosky | 176 | 212 | -36 |
| 1978-05-25 | vs KCA | 46 | L 4-9 | 16-30 | 6 | 5,946 | Glenn Abbott | Paul Splittorff | Paul Splittorff | Glenn Abbott | | 180 | 221 | -41 |
| 1978-05-26 | @ TEX | 47 | W 6-4 | 17-30 | 6 | 17,490 | Byron McLaughlin | Doyle Alexander | Shane Rawley | Doyle Alexander | Enrique Romo | 186 | 225 | -39 |
| 1978-05-27 | @ TEX | 48 | L 2-3 | 17-31 | 6 | 23,019 | Tom House | Jon Matlack | Jon Matlack | Tom House | Reggie Cleveland | 188 | 228 | -40 |
| 1978-05-29 | @ KCA | 49 | L 2-8 | 17-32 | 7 | 36,405 | Dick Pole | Rich Gale | Rich Gale | Dick Pole | | 190 | 236 | -46 |
| 1978-05-31 | @ KCA | 50 | L 3-8 | 17-33 | 7 | 17,071 | Glenn Abbott | Paul Splittorff | Paul Splittorff | Glenn Abbott | | 193 | 244 | -51 |
| 1978-06-01 | @ KCA | 51 | L 0-10 | 17-34 | 7 | 16,595 | Tom House | Dennis Leonard | Dennis Leonard | Tom House | | 193 | 254 | -61 |
| 1978-06-02 | vs BAL | 52 | L 9-10 | 17-35 | 7 | 4,936 | Jim Colborn | Dennis Martinez | Dennis Martinez | Jim Colborn | Don Stanhouse | 202 | 264 | -62 |
| 1978-06-03 | vs BAL | 53 | L 1-2 | 17-36 | 7 | 15,002 | Paul Mitchell | Scott McGregor | Scott McGregor | Paul Mitchell | Tippy Martinez | 203 | 266 | -63 |
| 1978-06-04 | vs BAL | 54 | L 1-4 | 17-37 | 7 | 6,429 | Dick Pole | Mike Flanagan | Mike Flanagan | Dick Pole | | 204 | 270 | -66 |
| 1978-06-05 | vs NYA | 55 | W 7-3 | 18-37 | 7 | 15,189 | Tom House | Ed Figueroa | Tom House | Ed Figueroa | | 211 | 273 | -62 |
| 1978-06-06 | vs NYA | 56 | W 4-3 | 19-37 | 7 | 12,638 | Byron McLaughlin | Dick Tidrow | Shane Rawley | Rich Gossage | | 215 | 276 | -61 |
| 1978-06-07 | vs NYA | 57 | L 1-9 | 19-38 | 7 | 12,544 | Jim Colborn | Ron Guidry | Ron Guidry | Jim Colborn | | 216 | 285 | -69 |
| 1978-06-09 | vs BOS | 58 | L 2-3 | 19-39 | 7 | 11,677 | Paul Mitchell | Luis Tiant | Luis Tiant | Paul Mitchell | | 218 | 288 | -70 |
| 1978-06-10 | vs BOS | 59 | L 1-13 | 19-40 | 7 | 15,910 | Dick Pole | Mike Torrez | Mike Torrez | Dick Pole | | 219 | 301 | -82 |
| 1978-06-11 | vs BOS | 60 | L 3-5 | 19-41 | 7 | 18,626 | Byron McLaughlin | Dennis Eckersley | Dennis Eckersley | Byron McLaughlin | Bill Campbell | 222 | 306 | -84 |
| 1978-06-12 | @ BAL | 61 | L 4-5 | 19-42 | 7 | 13,212 | Jim Colborn | Dennis Martinez | Tippy Martinez | Jim Colborn | Don Stanhouse | 226 | 311 | -85 |
| 1978-06-13 | @ BAL | 62 | L 2-3 | 19-43 | 7 | 7,729 | Glenn Abbott | Mike Flanagan | Mike Flanagan | Enrique Romo | | 228 | 314 | -86 |
| 1978-06-14 | @ NYA | 63 | L 9-11 | 19-44 | 7 | 18,015 | Tom House | Andy Messersmith | Sparky Lyle | John Montague | | 237 | 325 | -88 |
| 1978-06-15 | @ NYA | 64 | L 2-5 | 19-45 | 7 | 18,643 | Paul Mitchell | Don Gullett | Don Gullett | Paul Mitchell | Sparky Lyle | 239 | 330 | -91 |
| 1978-06-16 | @ BOS | 65 | L 3-6 | 19-46 | 7 | 31,519 | Dick Pole | Dennis Eckersley | Bill Campbell | Dick Pole | | 242 | 336 | -94 |
| 1978-06-17 | @ BOS | 66 | L 4-5 | 19-47 | 7 | 32,551 | Jim Colborn | Allen Ripley | Bob Stanley | John Montague | | 246 | 341 | -95 |
| 1978-06-18 | @ BOS | 67 | W 3-2 | 20-47 | 7 | 28,961 | Glenn Abbott | Jim Wright | Glenn Abbott | Jim Wright | | 249 | 343 | -94 |
| 1978-06-19 | @ CHA | 68 | W 7-4 | 21-47 | 7 | 22,322 | Mike Parrott | Jack Kucek | Mike Parrott | Jack Kucek | Enrique Romo | 256 | 347 | -91 |
| 1978-06-20 | @ CHA | 69 | W 4-2 | 22-47 | 7 | 13,057 | Paul Mitchell | Steve Stone | Paul Mitchell | Steve Stone | Enrique Romo | 260 | 349 | -89 |
| 1978-06-22 | @ CHA | 70 | W 8-6 | 23-47 | 7 | 22,026 | Dick Pole | Francisco Barrios | John Montague | Jim Willoughby | | 268 | 355 | -87 |
| 1978-06-23 | @ MIL | 71 | W 3-0 | 24-47 | 7 | 8,268 | Glenn Abbott | Mike Caldwell | Glenn Abbott | Mike Caldwell | | 271 | 355 | -84 |
| 1978-06-24 | @ MIL | 72 | L 0-5 | 24-48 | 7 | 20,820 | Jim Colborn | Jerry Augustine | Jerry Augustine | Jim Colborn | | 271 | 360 | -89 |
| 1978-06-25 | @ MIL | 73 | W 10-8 | 25-48 | 7 | 24,526 | Mike Parrott | Bill Travers | Enrique Romo | Randy Stein | John Montague | 281 | 368 | -87 |
| 1978-06-26 | vs CHA | 74 | W 8-3 | 26-48 | 7 | 9,147 | Paul Mitchell | Francisco Barrios | Paul Mitchell | Francisco Barrios | Shane Rawley | 289 | 371 | -82 |
| 1978-06-27 | vs CHA | 75 | L 6-10 | 26-49 | 7 | 10,259 | Dick Pole | Wilbur Wood | Wilbur Wood | Dick Pole | | 295 | 381 | -86 |
| 1978-06-28 | vs CHA | 76 | L 2-4 | 26-50 | 7 | 8,110 | Glenn Abbott | Ken Kravec | Ken Kravec | Glenn Abbott | Lerrin LaGrow | 297 | 385 | -88 |
| 1978-06-29 | vs CHA | 77 | W 9-7 | 27-50 | 7 | 7,568 | Jim Colborn | Steve Stone | Enrique Romo | Lerrin LaGrow | | 306 | 392 | -86 |
| 1978-06-30 | vs MIL | 78 | L 3-13 | 27-51 | 7 | 7,772 | Mike Parrott | Bill Travers | Bill Travers | Mike Parrott | Eduardo Rodriguez | 309 | 405 | -96 |
| 1978-07-01 | vs MIL | 79 | L 0-4 | 27-52 | 7 | 14,836 | Paul Mitchell | Lary Sorensen | Lary Sorensen | Paul Mitchell | | 309 | 409 | -100 |
| 1978-07-02 | vs MIL | 80 | W 4-3 | 28-52 | 7 | 9,904 | Dick Pole | Mike Caldwell | Shane Rawley | Bill Castro | | 313 | 412 | -99 |
| 1978-07-03 | vs OAK | 81 | L 3-5 | 28-53 | 7 | 9,489 | Glenn Abbott | Pete Broberg | Pete Broberg | Glenn Abbott | Dave Heaverlo | 316 | 417 | -101 |
| 1978-07-04 | vs OAK | 82 | L 4-9 | 28-54 | 7 | 10,942 | Rick Honeycutt | Craig Minetto | Elias Sosa | Rick Honeycutt | | 320 | 426 | -106 |
| 1978-07-05 | vs OAK | 83 | L 3-5 | 28-55 | 7 | 6,723 | Mike Parrott | Matt Keough | Matt Keough | Shane Rawley | Dave Heaverlo | 323 | 431 | -108 |
| 1978-07-06 | vs OAK | 84 | W 3-2 | 29-55 | 7 | 7,523 | Paul Mitchell | John Henry Johnson | Paul Mitchell | John Henry Johnson | Enrique Romo | 326 | 433 | -107 |
| 1978-07-07 | @ CAL | 85 | L 5-9 | 29-56 | 7 | 20,119 | Dick Pole | Frank Tanana | Frank Tanana | Dick Pole | Dave LaRoche | 331 | 442 | -111 |
| 1978-07-08 | @ CAL | 86 | L 5-10 | 29-58 | 7 | 0 | Glenn Abbott | Chris Knapp | Chris Knapp | Glenn Abbott | Dave LaRoche | 336 | 452 | -116 |
| 1978-07-08 | @ CAL | 87 | L 0-5 | 29-58 | 7 | 32,020 | Jim Colborn | Dave Frost | Dave Frost | Jim Colborn | | 336 | 457 | -121 |
| 1978-07-09 | @ CAL | 88 | W 11-7 | 30-58 | 7 | 20,969 | Rick Honeycutt | Nolan Ryan | Enrique Romo | Nolan Ryan | | 347 | 464 | -117 |
| 1978-07-13 | vs DET | 89 | W 5-4 | 31-58 | 7 | 7,449 | Glenn Abbott | Dave Rozema | Enrique Romo | Jim Crawford | | 352 | 468 | -116 |
| 1978-07-14 | vs DET | 90 | L 0-2 | 31-59 | 7 | 9,742 | Rick Honeycutt | Jim Slaton | Jim Slaton | Shane Rawley | | 352 | 470 | -118 |
| 1978-07-15 | vs CLE | 91 | W 7-6 | 32-59 | 7 | 26,117 | Mike Parrott | Mike Paxton | Enrique Romo | Mike Paxton | | 359 | 476 | -117 |
| 1978-07-16 | vs CLE | 92 | L 4-8 | 32-60 | 7 | 8,312 | Paul Mitchell | David Clyde | David Clyde | Paul Mitchell | Sid Monge | 363 | 484 | -121 |
| 1978-07-17 | vs CLE | 93 | L 2-5 | 32-61 | 7 | 7,676 | Jim Colborn | Dave Freisleben | Dave Freisleben | Jim Colborn | Sid Monge | 365 | 489 | -124 |
| 1978-07-18 | vs TOR | 94 | L 12-13 | 32-62 | 7 | 6,881 | Glenn Abbott | Dave Lemanczyk | Tom Murphy | Dick Pole | | 377 | 502 | -125 |
| 1978-07-19 | vs TOR | 95 | W 6-2 | 33-62 | 7 | 7,434 | Rick Honeycutt | Jesse Jefferson | Rick Honeycutt | Jesse Jefferson | John Montague | 383 | 504 | -121 |
| 1978-07-21 | @ CLE | 96 | L 0-11 | 33-63 | 7 | 13,908 | Mike Parrott | Mike Paxton | Mike Paxton | Mike Parrott | | 383 | 515 | -132 |
| 1978-07-22 | @ CLE | 97 | L 5-8 | 33-64 | 7 | 10,279 | Paul Mitchell | David Clyde | Paul Reuschel | Paul Mitchell | | 388 | 523 | -135 |
| 1978-07-24 | @ TOR | 98 | W 1-0 | 35-64 | 7 | 0 | Rick Honeycutt | Dave Lemanczyk | Rick Honeycutt | Dave Lemanczyk | | 389 | 523 | -134 |
| 1978-07-24 | @ TOR | 99 | W 7-2 | 35-64 | 7 | 16,291 | Jim Colborn | Jesse Jefferson | Jim Colborn | Jesse Jefferson | Enrique Romo | 396 | 525 | -129 |
| 1978-07-25 | @ TOR | 100 | W 4-2 | 36-64 | 7 | 14,103 | Glenn Abbott | Tom Underwood | Glenn Abbott | Tom Underwood | | 400 | 527 | -127 |
| 1978-07-26 | @ KCA | 101 | L 3-12 | 36-65 | 7 | 20,327 | Mike Parrott | Doug Bird | Doug Bird | Mike Parrott | Steve Mingori | 403 | 539 | -136 |
| 1978-07-27 | @ KCA | 102 | L 1-3 | 36-66 | 7 | 26,712 | Paul Mitchell | Larry Gura | Larry Gura | Paul Mitchell | | 404 | 542 | -138 |
| 1978-07-28 | @ DET | 103 | L 3-4 | 36-67 | 7 | 20,484 | Jim Colborn | Dave Rozema | Dave Rozema | Enrique Romo | | 407 | 546 | -139 |
| 1978-07-29 | @ DET | 104 | L 1-9 | 36-68 | 7 | 22,984 | Rick Honeycutt | Kip Young | Kip Young | Rick Honeycutt | | 408 | 555 | -147 |
| 1978-07-30 | @ DET | 105 | L 4-5 | 36-69 | 7 | 21,575 | Glenn Abbott | Milt Wilcox | Milt Wilcox | Glenn Abbott | Bob Sykes | 412 | 560 | -148 |
| 1978-08-01 | vs MIN | 106 | W 13-6 | 37-69 | 7 | 9,272 | Paul Mitchell | Stan Perzanowski | Tom House | Stan Perzanowski | | 425 | 566 | -141 |
| 1978-08-02 | vs MIN | 107 | W 3-1 | 38-69 | 7 | 8,394 | Jim Colborn | Geoff Zahn | Jim Colborn | Geoff Zahn | | 428 | 567 | -139 |
| 1978-08-03 | vs MIN | 108 | W 6-5 | 39-69 | 7 | 9,471 | Rick Honeycutt | Darrell Jackson | Enrique Romo | Mike Marshall | | 434 | 572 | -138 |
| 1978-08-04 | @ OAK | 109 | L 1-6 | 39-70 | 7 | 2,502 | Glenn Abbott | John Henry Johnson | John Henry Johnson | Glenn Abbott | | 435 | 578 | -143 |
| 1978-08-05 | @ OAK | 110 | W 3-2 | 40-70 | 7 | 2,677 | Byron McLaughlin | Matt Keough | Jim Todd | Matt Keough | | 438 | 580 | -142 |
| 1978-08-06 | @ OAK | 111 | L 3-4 | 40-72 | 7 | 0 | Paul Mitchell | Rick Langford | Rick Langford | Shane Rawley | | 441 | 584 | -143 |
| 1978-08-06 | @ OAK | 112 | L 3-4 | 40-72 | 7 | 4,898 | Tom House | Pete Broberg | Bob Lacey | Enrique Romo | | 444 | 588 | -144 |
| 1978-08-07 | @ MIN | 113 | W 6-5 | 41-72 | 7 | 6,657 | Jim Colborn | Darrell Jackson | Jim Todd | Stan Perzanowski | | 450 | 593 | -143 |
| 1978-08-08 | @ MIN | 114 | L 2-10 | 41-73 | 7 | 6,499 | Rick Honeycutt | Gary Serum | Gary Serum | Rick Honeycutt | | 452 | 603 | -151 |
| 1978-08-09 | @ MIN | 115 | W 4-1 | 42-73 | 7 | 6,814 | Glenn Abbott | Roger Erickson | Glenn Abbott | Roger Erickson | Jim Todd | 456 | 604 | -148 |
| 1978-08-11 | vs CAL | 116 | L 1-3 | 42-74 | 7 | 0 | Byron McLaughlin | Nolan Ryan | Nolan Ryan | Byron McLaughlin | | 457 | 607 | -150 |
| 1978-08-12 | vs CAL | 117 | L 5-7 | 43-75 | 7 | 0 | Jim Colborn | Don Aase | Dave LaRoche | Jim Todd | | 462 | 614 | -152 |
| 1978-08-12 | vs CAL | 118 | W 5-3 | 43-75 | 7 | 15,833 | Paul Mitchell | Chris Knapp | Paul Mitchell | Chris Knapp | Mike Parrott | 467 | 617 | -150 |
| 1978-08-13 | vs CAL | 119 | W 4-1 | 44-75 | 7 | 10,229 | Rick Honeycutt | Paul Hartzell | Rick Honeycutt | Paul Hartzell | | 471 | 618 | -147 |
| 1978-08-15 | vs BAL | 120 | L 4-7 | 44-76 | 7 | 7,999 | Glenn Abbott | Dennis Martinez | Dennis Martinez | Glenn Abbott | Don Stanhouse | 475 | 625 | -150 |
| 1978-08-16 | vs BAL | 121 | W 7-5 | 45-76 | 7 | 6,619 | Byron McLaughlin | Mike Flanagan | Byron McLaughlin | Mike Flanagan | Jim Todd | 482 | 630 | -148 |
| 1978-08-18 | vs NYA | 122 | L 1-6 | 45-77 | 7 | 19,824 | Paul Mitchell | Ed Figueroa | Ed Figueroa | Paul Mitchell | | 483 | 636 | -153 |
| 1978-08-19 | vs NYA | 123 | W 4-1 | 46-77 | 7 | 29,915 | Jim Colborn | Dick Tidrow | Jim Colborn | Dick Tidrow | | 487 | 637 | -150 |
| 1978-08-20 | vs NYA | 124 | W 5-4 | 47-77 | 7 | 21,834 | Rick Honeycutt | Ron Guidry | Enrique Romo | Rich Gossage | | 492 | 641 | -149 |
| 1978-08-22 | vs BOS | 125 | W 5-2 | 48-77 | 7 | 21,486 | Glenn Abbott | Luis Tiant | Glenn Abbott | Luis Tiant | | 497 | 643 | -146 |
| 1978-08-23 | vs BOS | 126 | W 5-3 | 49-77 | 7 | 22,718 | Byron McLaughlin | Mike Torrez | Byron McLaughlin | Mike Torrez | Enrique Romo | 502 | 646 | -144 |
| 1978-08-25 | @ BAL | 127 | L 0-5 | 49-78 | 7 | 10,538 | Paul Mitchell | Dennis Martinez | Dennis Martinez | Paul Mitchell | | 502 | 651 | -149 |
| 1978-08-26 | @ BAL | 128 | L 2-9 | 49-79 | 7 | 16,484 | Jim Colborn | Mike Flanagan | Mike Flanagan | Jim Colborn | Joe Kerrigan | 504 | 660 | -156 |
| 1978-08-27 | @ BAL | 129 | L 3-4 | 49-80 | 7 | 7,260 | Rick Honeycutt | Scott McGregor | Nelson Briles | Enrique Romo | | 507 | 664 | -157 |
| 1978-08-28 | @ BOS | 130 | L 9-10 | 49-81 | 7 | 24,301 | Glenn Abbott | Mike Torrez | Bob Stanley | Enrique Romo | | 516 | 674 | -158 |
| 1978-08-29 | @ BOS | 131 | L 5-10 | 49-82 | 7 | 32,393 | Byron McLaughlin | Dick Drago | Dick Drago | Byron McLaughlin | Tom Burgmeier | 521 | 684 | -163 |
| 1978-09-01 | @ NYA | 132 | W 3-0 | 50-82 | 7 | 20,167 | Paul Mitchell | Catfish Hunter | Paul Mitchell | Catfish Hunter | | 524 | 684 | -160 |
| 1978-09-02 | @ NYA | 133 | L 2-6 | 50-83 | 7 | 18,530 | Jim Colborn | Ed Figueroa | Ed Figueroa | Jim Colborn | | 526 | 690 | -164 |
| 1978-09-03 | @ NYA | 134 | L 3-4 | 50-84 | 7 | 22,386 | Rick Honeycutt | Jim Beattie | Jim Beattie | Rick Honeycutt | Rich Gossage | 529 | 694 | -165 |
| 1978-09-04 | @ MIL | 135 | W 4-3 | 51-85 | 7 | 0 | Glenn Abbott | Mike Caldwell | Glenn Abbott | Mike Caldwell | | 533 | 697 | -164 |
| 1978-09-04 | @ MIL | 136 | L 0-5 | 51-85 | 7 | 19,408 | Byron McLaughlin | Bill Travers | Bill Travers | Byron McLaughlin | | 533 | 702 | -169 |
| 1978-09-07 | @ CHA | 137 | W 5-3 | 52-85 | 7 | 2,514 | Paul Mitchell | Steve Stone | Paul Mitchell | Steve Stone | | 538 | 705 | -167 |
| 1978-09-08 | @ CHA | 138 | L 2-3 | 52-86 | 7 | 30,270 | Jim Colborn | Rich Wortham | Rich Wortham | Jim Colborn | | 540 | 708 | -168 |
| 1978-09-09 | @ CHA | 139 | W 9-6 | 53-86 | 7 | 6,941 | Rick Honeycutt | Francisco Barrios | Enrique Romo | Lerrin LaGrow | | 549 | 714 | -165 |
| 1978-09-10 | @ CHA | 140 | L 1-2 | 53-87 | 7 | 17,205 | Glenn Abbott | Jack Kucek | Jack Kucek | Glenn Abbott | | 550 | 716 | -166 |
| 1978-09-11 | vs MIL | 141 | L 3-5 | 53-88 | 7 | 5,246 | Byron McLaughlin | Lary Sorensen | Lary Sorensen | Byron McLaughlin | Bill Castro | 553 | 721 | -168 |
| 1978-09-12 | vs MIL | 142 | W 6-5 | 54-88 | 7 | 5,577 | Paul Mitchell | Mark Bomback | Jim Todd | Bob McClure | | 559 | 726 | -167 |
| 1978-09-14 | vs CHA | 143 | L 5-6 | 54-89 | 7 | 5,310 | Rick Honeycutt | Steve Stone | Steve Stone | Rick Honeycutt | | 564 | 732 | -168 |
| 1978-09-15 | vs CHA | 144 | L 3-8 | 54-90 | 7 | 4,849 | Jim Colborn | Rich Wortham | Rich Wortham | Enrique Romo | | 567 | 740 | -173 |
| 1978-09-16 | vs CHA | 145 | L 1-9 | 54-91 | 7 | 11,230 | Glenn Abbott | Francisco Barrios | Francisco Barrios | Glenn Abbott | | 568 | 749 | -181 |
| 1978-09-17 | vs CHA | 146 | W 3-1 | 55-91 | 7 | 6,071 | Byron McLaughlin | Jack Kucek | Byron McLaughlin | Jack Kucek | | 571 | 750 | -179 |
| 1978-09-18 | vs KCA | 147 | L 6-7 | 55-92 | 7 | 5,766 | Paul Mitchell | Larry Gura | Doug Bird | Mike Parrott | Al Hrabosky | 577 | 757 | -180 |
| 1978-09-19 | vs KCA | 148 | L 8-9 | 55-93 | 7 | 5,946 | Rick Honeycutt | Paul Splittorff | Paul Splittorff | Rick Honeycutt | | 585 | 766 | -181 |
| 1978-09-22 | @ TEX | 149 | L 2-10 | 55-95 | 7 | 0 | Glenn Abbott | Doc Medich | Doc Medich | Glenn Abbott | | 587 | 776 | -189 |
| 1978-09-22 | @ TEX | 150 | L 0-1 | 55-95 | 7 | 7,861 | Byron McLaughlin | Fergie Jenkins | Fergie Jenkins | Byron McLaughlin | | 587 | 777 | -190 |
| 1978-09-23 | @ TEX | 151 | L 2-7 | 55-96 | 7 | 10,526 | Paul Mitchell | Doyle Alexander | Doyle Alexander | Paul Mitchell | | 589 | 784 | -195 |
| 1978-09-24 | @ TEX | 152 | L 3-5 | 55-98 | 7 | 0 | Jim Colborn | Steve Comer | Steve Comer | Jim Colborn | Paul Mirabella | 592 | 789 | -197 |
| 1978-09-24 | @ TEX | 153 | L 3-4 | 55-98 | 7 | 6,955 | Rick Jones | Danny Darwin | Danny Darwin | Rick Jones | Jim Umbarger | 595 | 793 | -198 |
| 1978-09-25 | @ KCA | 154 | L 2-7 | 55-99 | 7 | 21,890 | Rick Honeycutt | Dennis Leonard | Dennis Leonard | Rick Honeycutt | | 597 | 800 | -203 |
| 1978-09-26 | @ KCA | 155 | L 1-4 | 55-100 | 7 | 22,415 | Glenn Abbott | Larry Gura | Larry Gura | Glenn Abbott | | 598 | 804 | -206 |
| 1978-09-27 | @ KCA | 156 | W 4-2 | 56-100 | 7 | 14,737 | Byron McLaughlin | Paul Splittorff | Byron McLaughlin | Paul Splittorff | | 602 | 806 | -204 |
| 1978-09-28 | vs TEX | 157 | L 3-4 | 56-101 | 7 | 4,768 | Shane Rawley | Doyle Alexander | Jim Umbarger | Shane Rawley | | 605 | 810 | -205 |
| 1978-09-29 | vs TEX | 158 | L 4-11 | 56-102 | 7 | 5,998 | Mike Parrott | Steve Comer | Steve Comer | Mike Parrott | | 609 | 821 | -212 |
| 1978-09-30 | vs TEX | 159 | L 1-4 | 56-103 | 7 | 12,132 | Rick Jones | Jon Matlack | Jon Matlack | Rick Jones | | 610 | 825 | -215 |
| 1978-10-01 | vs TEX | 160 | L 4-9 | 56-104 | 7 | 5,807 | Glenn Abbott | Fergie Jenkins | Fergie Jenkins | Glenn Abbott | | 614 | 834 | -220 |