| 1965-04-12 | @ KC1 | 1 | W 6-2 | 1-0 | 3 | 18,109 | Mickey Lolich | Moe Drabowsky | Mickey Lolich | Moe Drabowsky | Larry Sherry | 6 | 2 | 4 |
| 1965-04-13 | @ KC1 | 2 | W 11-4 | 2-0 | 5 | 2,028 | Hank Aguirre | Diego Segui | Hank Aguirre | Diego Segui | Denny McLain | 17 | 6 | 11 |
| 1965-04-15 | @ MIN | 3 | W 6-4 | 3-0 | 1 | 2,382 | Dave Wickersham | Camilo Pascual | Dave Wickersham | Jerry Fosnow | | 23 | 10 | 13 |
| 1965-04-17 | @ CAL | 4 | L 1-3 | 3-1 | 1 | 10,460 | Phil Regan | Fred Newman | Fred Newman | Phil Regan | | 24 | 13 | 11 |
| 1965-04-18 | @ CAL | 5 | W 4-1 | 4-1 | 1 | 8,672 | Denny McLain | Rudy May | Terry Fox | Bob Lee | | 28 | 14 | 14 |
| 1965-04-19 | @ CAL | 6 | L 2-4 | 4-2 | 3 | 5,136 | Mickey Lolich | Marcelino Lopez | Marcelino Lopez | Mickey Lolich | | 30 | 18 | 12 |
| 1965-04-21 | vs KC1 | 7 | W 1-0 | 5-2 | 2 | 32,658 | Hank Aguirre | John O'Donoghue | Hank Aguirre | John O'Donoghue | Larry Sherry | 31 | 18 | 13 |
| 1965-04-23 | vs MIN | 8 | L 6-8 | 5-3 | 3 | 12,038 | Dave Wickersham | Mudcat Grant | Al Worthington | Julio Navarro | | 37 | 26 | 11 |
| 1965-04-24 | vs MIN | 9 | W 7-4 | 6-3 | 3 | 3,596 | Phil Regan | Dick Stigman | Larry Sherry | Jerry Fosnow | | 44 | 30 | 14 |
| 1965-04-27 | vs CAL | 10 | L 3-4 | 6-4 | 3 | 4,872 | Denny McLain | Fred Newman | Fred Newman | Denny McLain | Bob Lee | 47 | 34 | 13 |
| 1965-04-28 | vs CAL | 11 | W 5-4 | 7-4 | 3 | 4,621 | Mickey Lolich | Dean Chance | Mickey Lolich | George Brunet | Larry Sherry | 52 | 38 | 14 |
| 1965-04-30 | vs BOS | 12 | W 4-1 | 8-4 | 3 | 8,800 | Hank Aguirre | Dave Morehead | Hank Aguirre | Dave Morehead | | 56 | 39 | 17 |
| 1965-05-01 | vs BOS | 13 | W 9-8 | 9-4 | 2 | 3,854 | Dave Wickersham | Jim Lonborg | Mickey Lolich | Jack Lamabe | | 65 | 47 | 18 |
| 1965-05-02 | vs BOS | 14 | L 1-2 | 9-6 | 3 | 0 | Phil Regan | Earl Wilson | Earl Wilson | Phil Regan | Dick Radatz | 66 | 49 | 17 |
| 1965-05-02 | vs BOS | 15 | L 3-10 | 9-6 | 3 | 22,011 | Joe Sparma | Bill Monbouquette | Bill Monbouquette | Joe Sparma | | 69 | 59 | 10 |
| 1965-05-04 | vs CHA | 16 | L 6-10 | 9-7 | 3 | 3,751 | Denny McLain | Gary Peters | Ted Wills | Denny McLain | | 75 | 69 | 6 |
| 1965-05-05 | vs CHA | 17 | L 0-4 | 9-9 | 6 | 0 | Mickey Lolich | John Buzhardt | John Buzhardt | Mickey Lolich | | 75 | 73 | 2 |
| 1965-05-05 | vs CHA | 18 | L 1-4 | 9-9 | 6 | 9,380 | Dave Wickersham | Joe Horlen | Joe Horlen | Dave Wickersham | | 76 | 77 | -1 |
| 1965-05-08 | @ BAL | 19 | W 4-3 | 10-9 | 5 | 3,683 | Hank Aguirre | Dave McNally | Terry Fox | Dick Hall | | 80 | 80 | 0 |
| 1965-05-09 | @ BAL | 20 | L 1-7 | 10-11 | 6 | 0 | Phil Regan | Milt Pappas | Milt Pappas | Phil Regan | | 81 | 87 | -6 |
| 1965-05-09 | @ BAL | 21 | L 4-5 | 10-11 | 6 | 12,086 | Denny McLain | Jim Palmer | Dick Hall | Fred Gladding | | 85 | 92 | -7 |
| 1965-05-10 | @ BAL | 22 | W 5-4 | 11-11 | 6 | 7,616 | Mickey Lolich | Robin Roberts | Mickey Lolich | Robin Roberts | Terry Fox | 90 | 96 | -6 |
| 1965-05-11 | @ WS2 | 23 | W 7-6 | 12-11 | 6 | 6,066 | Dave Wickersham | Frank Kreutzer | Larry Sherry | Ron Kline | | 97 | 102 | -5 |
| 1965-05-12 | @ WS2 | 24 | W 5-2 | 13-11 | 5 | 3,205 | Joe Sparma | Mike McCormick | Joe Sparma | Mike McCormick | Mickey Lolich | 102 | 104 | -2 |
| 1965-05-13 | @ WS2 | 25 | W 13-3 | 14-11 | 5 | 3,361 | Hank Aguirre | Bennie Daniels | Hank Aguirre | Bennie Daniels | | 115 | 107 | 8 |
| 1965-05-14 | @ BOS | 26 | W 12-8 | 15-11 | 3 | 10,271 | Denny McLain | Dennis Bennett | Terry Fox | Dick Radatz | | 127 | 115 | 12 |
| 1965-05-15 | @ BOS | 27 | W 6-2 | 16-11 | 3 | 6,514 | Mickey Lolich | Jim Lonborg | Mickey Lolich | Jim Lonborg | Larry Sherry | 133 | 117 | 16 |
| 1965-05-16 | @ BOS | 28 | L 0-5 | 16-13 | 4 | 0 | Dave Wickersham | Earl Wilson | Earl Wilson | Dave Wickersham | | 133 | 122 | 11 |
| 1965-05-16 | @ BOS | 29 | L 3-4 | 16-13 | 4 | 18,244 | Joe Sparma | Bill Monbouquette | Bill Monbouquette | Joe Sparma | Dick Radatz | 136 | 126 | 10 |
| 1965-05-18 | vs WS2 | 30 | L 9-15 | 16-14 | 5 | 8,841 | Hank Aguirre | Phil Ortega | Phil Ortega | Hank Aguirre | Steve Ridzik | 145 | 141 | 4 |
| 1965-05-19 | vs WS2 | 31 | W 4-0 | 17-14 | 3 | 5,309 | Denny McLain | Bennie Daniels | Denny McLain | Bennie Daniels | | 149 | 141 | 8 |
| 1965-05-20 | vs WS2 | 32 | W 9-8 | 18-14 | 3 | 3,510 | Mickey Lolich | Frank Kreutzer | Jack Hamilton | Marshall Bridges | | 158 | 149 | 9 |
| 1965-05-21 | vs BAL | 33 | L 2-5 | 18-15 | 4 | 15,039 | Dave Wickersham | Milt Pappas | Milt Pappas | Dave Wickersham | Stu Miller | 160 | 154 | 6 |
| 1965-05-22 | vs BAL | 34 | W 8-4 | 19-15 | 3 | 6,237 | Joe Sparma | Robin Roberts | Joe Sparma | Robin Roberts | Ron Nischwitz | 168 | 158 | 10 |
| 1965-05-23 | vs BAL | 35 | L 3-7 | 19-17 | 4 | 0 | Hank Aguirre | Steve Barber | Steve Barber | Hank Aguirre | Stu Miller | 171 | 165 | 6 |
| 1965-05-23 | vs BAL | 36 | L 3-8 | 19-17 | 4 | 17,143 | Jack Hamilton | Dave McNally | Dave McNally | Jack Hamilton | Stu Miller | 174 | 173 | 1 |
| 1965-05-24 | @ CHA | 37 | W 8-3 | 20-17 | 4 | 13,654 | Mickey Lolich | John Buzhardt | Mickey Lolich | John Buzhardt | | 182 | 176 | 6 |
| 1965-05-25 | @ CHA | 38 | W 7-5 | 21-17 | 4 | 13,130 | Dave Wickersham | Tommy John | Fred Gladding | Tommy John | Terry Fox | 189 | 181 | 8 |
| 1965-05-27 | vs NYA | 39 | W 4-1 | 22-17 | 3 | 18,257 | Joe Sparma | Whitey Ford | Joe Sparma | Whitey Ford | | 193 | 182 | 11 |
| 1965-05-28 | vs CLE | 40 | W 1-0 | 23-17 | 3 | 11,291 | Hank Aguirre | Ralph Terry | Hank Aguirre | Ralph Terry | | 194 | 182 | 12 |
| 1965-05-29 | vs CLE | 41 | W 1-0 | 24-17 | 3 | 5,953 | Mickey Lolich | Jack Kralick | Mickey Lolich | Jack Kralick | | 195 | 182 | 13 |
| 1965-05-30 | vs CLE | 42 | L 2-10 | 24-18 | 3 | 17,524 | Phil Regan | Sam McDowell | Sam McDowell | Phil Regan | | 197 | 192 | 5 |
| 1965-05-31 | @ NYA | 43 | L 1-3 | 25-19 | 3 | 0 | Denny McLain | Whitey Ford | Whitey Ford | Denny McLain | Pedro Ramos | 198 | 195 | 3 |
| 1965-05-31 | @ NYA | 44 | W 5-1 | 25-19 | 3 | 31,442 | Joe Sparma | Gil Blanco | Joe Sparma | Gil Blanco | | 203 | 196 | 7 |
| 1965-06-04 | @ CLE | 45 | L 6-7 | 25-20 | 3 | 17,693 | Hank Aguirre | Ralph Terry | Sonny Siebert | Larry Sherry | Gary Bell | 209 | 203 | 6 |
| 1965-06-05 | @ CLE | 46 | L 1-2 | 25-21 | 4 | 13,084 | Mickey Lolich | Sam McDowell | Sam McDowell | Terry Fox | | 210 | 205 | 5 |
| 1965-06-06 | @ CLE | 47 | L 1-10 | 25-22 | 5 | 29,183 | Joe Sparma | Jack Kralick | Jack Kralick | Joe Sparma | Gary Bell | 211 | 215 | -4 |
| 1965-06-07 | @ CAL | 48 | W 6-5 | 26-22 | 4 | 4,420 | Denny McLain | Dean Chance | Larry Sherry | Bob Lee | Terry Fox | 217 | 220 | -3 |
| 1965-06-08 | @ CAL | 49 | L 1-3 | 26-23 | 4 | 4,516 | Dave Wickersham | Fred Newman | Fred Newman | Dave Wickersham | | 218 | 223 | -5 |
| 1965-06-09 | @ CAL | 50 | W 4-2 | 27-23 | 4 | 5,515 | Hank Aguirre | Marcelino Lopez | Hank Aguirre | Marcelino Lopez | | 222 | 225 | -3 |
| 1965-06-11 | vs MIN | 51 | L 4-5 | 27-25 | 5 | 0 | Joe Sparma | Mudcat Grant | Dick Stigman | Terry Fox | | 226 | 230 | -4 |
| 1965-06-11 | vs MIN | 52 | L 4-5 | 27-25 | 5 | 30,716 | Mickey Lolich | Mel Nelson | Jim Perry | Terry Fox | | 230 | 235 | -5 |
| 1965-06-12 | vs MIN | 53 | W 8-5 | 28-25 | 5 | 7,493 | Denny McLain | Camilo Pascual | Denny McLain | Jerry Fosnow | Fred Gladding | 238 | 240 | -2 |
| 1965-06-13 | vs MIN | 54 | W 5-4 | 29-25 | 5 | 50,383 | Hank Aguirre | Jim Kaat | Hank Aguirre | Jim Kaat | Mickey Lolich | 243 | 244 | -1 |
| 1965-06-15 | vs BOS | 55 | W 6-5 | 30-25 | 5 | 9,624 | Dave Wickersham | Earl Wilson | Fred Gladding | Dick Radatz | | 249 | 249 | 0 |
| 1965-06-16 | vs BOS | 56 | W 9-4 | 31-25 | 5 | 7,736 | Mickey Lolich | Dave Morehead | Fred Gladding | Bob Duliba | | 258 | 253 | 5 |
| 1965-06-17 | vs BOS | 57 | W 6-5 | 32-25 | 5 | 6,094 | Joe Sparma | Jerry Stephenson | Terry Fox | Jack Lamabe | | 264 | 258 | 6 |
| 1965-06-18 | vs KC1 | 58 | W 3-1 | 33-25 | 4 | 12,073 | Hank Aguirre | John O'Donoghue | Hank Aguirre | John O'Donoghue | | 267 | 259 | 8 |
| 1965-06-19 | vs KC1 | 59 | W 8-2 | 34-25 | 4 | 6,914 | Denny McLain | Diego Segui | Denny McLain | Diego Segui | | 275 | 261 | 14 |
| 1965-06-20 | vs KC1 | 60 | W 12-8 | 35-26 | 5 | 0 | Mickey Lolich | Catfish Hunter | Joe Sparma | Diego Segui | Fred Gladding | 287 | 269 | 18 |
| 1965-06-20 | vs KC1 | 61 | L 1-2 | 35-26 | 5 | 20,127 | Dave Wickersham | Rollie Sheldon | Rollie Sheldon | Dave Wickersham | | 288 | 271 | 17 |
| 1965-06-22 | vs CAL | 62 | L 0-3 | 35-27 | 5 | 17,516 | Mickey Lolich | George Brunet | George Brunet | Mickey Lolich | | 288 | 274 | 14 |
| 1965-06-23 | vs CAL | 63 | W 2-0 | 36-27 | 5 | 9,494 | Hank Aguirre | Rudy May | Hank Aguirre | Rudy May | | 290 | 274 | 16 |
| 1965-06-24 | vs CAL | 64 | W 3-2 | 37-27 | 5 | 6,382 | Denny McLain | Fred Newman | Denny McLain | Fred Newman | | 293 | 276 | 17 |
| 1965-06-25 | @ MIN | 65 | L 3-4 | 37-28 | 5 | 26,998 | Dave Wickersham | Dave Boswell | Johnny Klippstein | Dave Wickersham | | 296 | 280 | 16 |
| 1965-06-26 | @ MIN | 66 | W 5-2 | 38-28 | 5 | 20,181 | Mickey Lolich | Bill Pleis | Mickey Lolich | Bill Pleis | Terry Fox | 301 | 282 | 19 |
| 1965-06-27 | @ MIN | 67 | L 4-6 | 38-30 | 5 | 0 | Joe Sparma | Mudcat Grant | Al Worthington | Fred Gladding | | 305 | 288 | 17 |
| 1965-06-27 | @ MIN | 68 | L 5-6 | 38-30 | 5 | 32,146 | Hank Aguirre | Mel Nelson | Bill Pleis | Larry Sherry | | 310 | 294 | 16 |
| 1965-06-28 | @ BAL | 69 | W 4-3 | 39-30 | 4 | 13,215 | Denny McLain | Wally Bunker | Denny McLain | Wally Bunker | Orlando Pena | 314 | 297 | 17 |
| 1965-06-29 | @ BAL | 70 | L 2-3 | 39-31 | 5 | 9,425 | Dave Wickersham | Milt Pappas | Stu Miller | Dave Wickersham | | 316 | 300 | 16 |
| 1965-07-01 | @ BOS | 71 | W 2-1 | 40-31 | 5 | 3,863 | Mickey Lolich | Earl Wilson | Orlando Pena | Earl Wilson | | 318 | 301 | 17 |
| 1965-07-02 | @ WS2 | 72 | L 0-6 | 40-32 | 5 | 6,298 | Hank Aguirre | Frank Kreutzer | Frank Kreutzer | Hank Aguirre | | 318 | 307 | 11 |
| 1965-07-03 | @ WS2 | 73 | W 1-0 | 41-32 | 5 | 3,447 | Denny McLain | Pete Richert | Denny McLain | Pete Richert | | 319 | 307 | 12 |
| 1965-07-04 | @ WS2 | 74 | L 3-6 | 41-33 | 5 | 9,603 | Dave Wickersham | Buster Narum | Buster Narum | Dave Wickersham | Ron Kline | 322 | 313 | 9 |
| 1965-07-05 | vs NYA | 75 | L 2-7 | 42-34 | 5 | 0 | Mickey Lolich | Whitey Ford | Whitey Ford | Mickey Lolich | | 324 | 320 | 4 |
| 1965-07-05 | vs NYA | 76 | W 5-4 | 42-34 | 5 | 40,153 | Joe Sparma | Steve Hamilton | Joe Sparma | Hal Reniff | Orlando Pena | 329 | 324 | 5 |
| 1965-07-06 | vs NYA | 77 | W 8-0 | 43-34 | 5 | 22,052 | Denny McLain | Mel Stottlemyre | Denny McLain | Mel Stottlemyre | | 337 | 324 | 13 |
| 1965-07-07 | vs NYA | 78 | L 3-4 | 43-35 | 5 | 23,789 | Hank Aguirre | Al Downing | Al Downing | Hank Aguirre | | 340 | 328 | 12 |
| 1965-07-08 | vs NYA | 79 | W 6-1 | 44-35 | 5 | 24,559 | Mickey Lolich | Pete Mikkelsen | Mickey Lolich | Pete Mikkelsen | | 346 | 329 | 17 |
| 1965-07-09 | @ KC1 | 80 | W 7-5 | 45-35 | 5 | 5,772 | Joe Sparma | Fred Talbot | Fred Gladding | John O'Donoghue | Larry Sherry | 353 | 334 | 19 |
| 1965-07-10 | @ KC1 | 81 | L 3-4 | 45-36 | 5 | 6,080 | Denny McLain | Rollie Sheldon | Don Mossi | Larry Sherry | | 356 | 338 | 18 |
| 1965-07-11 | @ KC1 | 82 | W 4-2 | 46-36 | 5 | 5,874 | Hank Aguirre | Wes Stock | Hank Aguirre | Wes Stock | | 360 | 340 | 20 |
| 1965-07-15 | vs BAL | 83 | W 5-4 | 47-36 | 5 | 16,217 | Mickey Lolich | Steve Barber | Fred Gladding | Stu Miller | | 365 | 344 | 21 |
| 1965-07-16 | vs BAL | 84 | L 1-2 | 47-37 | 5 | 15,327 | Denny McLain | Milt Pappas | Harvey Haddix | Larry Sherry | | 366 | 346 | 20 |
| 1965-07-18 | vs BAL | 85 | L 1-4 | 47-38 | 5 | 43,313 | Hank Aguirre | Wally Bunker | Wally Bunker | Hank Aguirre | | 367 | 350 | 17 |
| 1965-07-19 | vs WS2 | 86 | L 0-8 | 47-39 | 5 | 4,986 | Mickey Lolich | Phil Ortega | Phil Ortega | Mickey Lolich | | 367 | 358 | 9 |
| 1965-07-20 | vs WS2 | 87 | W 2-0 | 48-39 | 5 | 7,278 | Dave Wickersham | Howie Koplitz | Dave Wickersham | Howie Koplitz | | 369 | 358 | 11 |
| 1965-07-21 | vs CLE | 88 | W 10-5 | 50-39 | 5 | 0 | Mickey Lolich | Sam McDowell | Mickey Lolich | Sam McDowell | Terry Fox | 379 | 363 | 16 |
| 1965-07-21 | vs CLE | 89 | W 2-1 | 50-39 | 5 | 32,704 | Denny McLain | Sonny Siebert | Denny McLain | Sonny Siebert | | 381 | 364 | 17 |
| 1965-07-23 | vs CHA | 90 | W 6-5 | 51-39 | 4 | 25,058 | Hank Aguirre | John Buzhardt | Orlando Pena | Bob Locker | | 387 | 369 | 18 |
| 1965-07-24 | vs CHA | 91 | W 7-4 | 52-39 | 4 | 10,994 | Dave Wickersham | Joe Horlen | Dave Wickersham | Joe Horlen | Julio Navarro | 394 | 373 | 21 |
| 1965-07-25 | vs CHA | 92 | L 6-10 | 53-40 | 4 | 0 | Mickey Lolich | Tommy John | Tommy John | Mickey Lolich | Hoyt Wilhelm | 400 | 383 | 17 |
| 1965-07-25 | vs CHA | 93 | W 13-2 | 53-40 | 4 | 36,799 | Denny McLain | Bruce Howard | Denny McLain | Bruce Howard | | 413 | 385 | 28 |
| 1965-07-27 | @ NYA | 94 | L 3-4 | 54-41 | 4 | 0 | Hank Aguirre | Whitey Ford | Whitey Ford | Hank Aguirre | Steve Hamilton | 416 | 389 | 27 |
| 1965-07-27 | @ NYA | 95 | W 3-0 | 54-41 | 4 | 21,598 | Joe Sparma | Jim Bouton | Joe Sparma | Jim Bouton | Fred Gladding | 419 | 389 | 30 |
| 1965-07-28 | @ NYA | 96 | W 4-3 | 55-41 | 4 | 14,474 | Dave Wickersham | Jack Cullen | Dave Wickersham | Steve Hamilton | Terry Fox | 423 | 392 | 31 |
| 1965-07-29 | @ NYA | 97 | L 3-7 | 55-42 | 4 | 22,714 | Denny McLain | Mel Stottlemyre | Mel Stottlemyre | Denny McLain | | 426 | 399 | 27 |
| 1965-07-30 | @ CHA | 98 | W 3-1 | 56-42 | 4 | 26,824 | Mickey Lolich | Juan Pizarro | Mickey Lolich | Eddie Fisher | Fred Gladding | 429 | 400 | 29 |
| 1965-07-31 | @ CHA | 99 | L 3-4 | 56-43 | 4 | 6,405 | Joe Sparma | Frank Lary | Frank Lary | Joe Sparma | John Buzhardt | 432 | 404 | 28 |
| 1965-08-01 | @ CHA | 100 | L 0-1 | 57-44 | 4 | 0 | Hank Aguirre | Joe Horlen | Joe Horlen | Hank Aguirre | | 432 | 405 | 27 |
| 1965-08-01 | @ CHA | 101 | W 2-1 | 57-44 | 4 | 18,266 | Dave Wickersham | Tommy John | Dave Wickersham | Tommy John | Mickey Lolich | 434 | 406 | 28 |
| 1965-08-02 | @ CHA | 102 | L 0-2 | 57-45 | 4 | 13,705 | Denny McLain | Gary Peters | Gary Peters | Denny McLain | Hoyt Wilhelm | 434 | 408 | 26 |
| 1965-08-03 | @ CLE | 103 | W 12-7 | 58-45 | 4 | 9,372 | Mickey Lolich | Steve Hargan | Terry Fox | Lee Stange | | 446 | 415 | 31 |
| 1965-08-04 | @ CLE | 104 | L 1-4 | 58-46 | 4 | 17,796 | Joe Sparma | Sonny Siebert | Sonny Siebert | Joe Sparma | | 447 | 419 | 28 |
| 1965-08-05 | @ CLE | 105 | L 2-5 | 58-47 | 4 | 13,639 | Dave Wickersham | Sam McDowell | Sam McDowell | Dave Wickersham | | 449 | 424 | 25 |
| 1965-08-06 | vs NYA | 106 | W 5-4 | 59-47 | 4 | 33,653 | Mickey Lolich | Jack Cullen | Orlando Pena | Pedro Ramos | | 454 | 428 | 26 |
| 1965-08-07 | vs NYA | 107 | L 5-6 | 59-48 | 5 | 34,625 | Hank Aguirre | Mel Stottlemyre | Mel Stottlemyre | Hank Aguirre | Whitey Ford | 459 | 434 | 25 |
| 1965-08-08 | vs NYA | 108 | L 5-6 | 59-49 | 5 | 23,684 | Denny McLain | Al Downing | Hal Reniff | Orlando Pena | | 464 | 440 | 24 |
| 1965-08-10 | vs KC1 | 109 | W 3-0 | 60-49 | 5 | 7,529 | Dave Wickersham | Fred Talbot | Dave Wickersham | Fred Talbot | | 467 | 440 | 27 |
| 1965-08-11 | vs KC1 | 110 | W 6-2 | 62-49 | 4 | 0 | Joe Sparma | Catfish Hunter | Joe Sparma | Catfish Hunter | | 473 | 442 | 31 |
| 1965-08-11 | vs KC1 | 111 | W 5-4 | 62-49 | 4 | 12,937 | Mickey Lolich | Rollie Sheldon | Fred Gladding | Jack Aker | | 478 | 446 | 32 |
| 1965-08-12 | vs KC1 | 112 | W 11-1 | 63-49 | 4 | 6,329 | Hank Aguirre | Diego Segui | Hank Aguirre | Diego Segui | | 489 | 447 | 42 |
| 1965-08-13 | vs CAL | 113 | W 2-1 | 64-49 | 4 | 13,777 | Denny McLain | Dean Chance | Denny McLain | Dean Chance | | 491 | 448 | 43 |
| 1965-08-14 | vs CAL | 114 | L 2-5 | 64-50 | 4 | 8,818 | Dave Wickersham | Marcelino Lopez | Marcelino Lopez | Dave Wickersham | Bob Lee | 493 | 453 | 40 |
| 1965-08-15 | vs CAL | 115 | W 9-2 | 66-50 | 2 | 0 | Joe Sparma | Ken McBride | Joe Sparma | Ken McBride | | 502 | 455 | 47 |
| 1965-08-15 | vs CAL | 116 | W 9-5 | 66-50 | 2 | 16,792 | Mickey Lolich | George Brunet | Orlando Pena | Ed Sukla | Terry Fox | 511 | 460 | 51 |
| 1965-08-17 | vs MIN | 117 | W 7-4 | 67-50 | 2 | 33,677 | Hank Aguirre | Jim Merritt | Hank Aguirre | Jim Merritt | Terry Fox | 518 | 464 | 54 |
| 1965-08-19 | vs MIN | 118 | L 3-8 | 67-52 | 4 | 0 | Dave Wickersham | Mudcat Grant | Mudcat Grant | Dave Wickersham | | 521 | 472 | 49 |
| 1965-08-19 | vs MIN | 119 | L 1-2 | 67-52 | 4 | 36,076 | Mickey Lolich | Jim Kaat | Jim Kaat | Orlando Pena | | 522 | 474 | 48 |
| 1965-08-20 | @ BOS | 120 | W 2-0 | 69-52 | 3 | 0 | Denny McLain | Bill Monbouquette | Denny McLain | Bill Monbouquette | | 524 | 474 | 50 |
| 1965-08-20 | @ BOS | 121 | W 3-2 | 69-52 | 3 | 11,829 | Joe Sparma | Earl Wilson | Dave Wickersham | Earl Wilson | Orlando Pena | 527 | 476 | 51 |
| 1965-08-21 | @ BOS | 122 | L 10-13 | 69-53 | 3 | 7,567 | Hank Aguirre | Dave Morehead | Bob Duliba | Hank Aguirre | | 537 | 489 | 48 |
| 1965-08-22 | @ BOS | 123 | W 2-1 | 70-53 | 3 | 7,272 | Joe Sparma | Dennis Bennett | Joe Sparma | Dennis Bennett | | 539 | 490 | 49 |
| 1965-08-23 | @ KC1 | 124 | L 3-4 | 70-54 | 3 | 3,414 | Mickey Lolich | Rollie Sheldon | Rollie Sheldon | Julio Navarro | John Wyatt | 542 | 494 | 48 |
| 1965-08-24 | @ KC1 | 125 | W 8-2 | 71-54 | 3 | 4,437 | Denny McLain | Lew Krausse | Denny McLain | Lew Krausse | | 550 | 496 | 54 |
| 1965-08-25 | @ KC1 | 126 | L 0-5 | 71-55 | 3 | 4,794 | Joe Sparma | Catfish Hunter | Catfish Hunter | Joe Sparma | | 550 | 501 | 49 |
| 1965-08-26 | @ KC1 | 127 | L 3-5 | 71-56 | 4 | 3,806 | Hank Aguirre | Fred Talbot | Jim Dickson | Larry Sherry | John Wyatt | 553 | 506 | 47 |
| 1965-08-27 | @ CAL | 128 | L 2-3 | 71-57 | 4 | 7,323 | Mickey Lolich | Dean Chance | Dean Chance | Mickey Lolich | Bob Lee | 555 | 509 | 46 |
| 1965-08-28 | @ CAL | 129 | L 3-4 | 71-58 | 5 | 5,571 | Denny McLain | Marcelino Lopez | Jim Coates | Orlando Pena | Jack Sanford | 558 | 513 | 45 |
| 1965-08-29 | @ CAL | 130 | W 2-1 | 72-58 | 4 | 5,132 | Joe Sparma | Fred Newman | Joe Sparma | Fred Newman | | 560 | 514 | 46 |
| 1965-08-30 | @ MIN | 131 | L 2-3 | 72-59 | 5 | 15,647 | Hank Aguirre | Jim Kaat | Johnny Klippstein | Larry Sherry | | 562 | 517 | 45 |
| 1965-08-31 | @ MIN | 132 | W 7-6 | 73-59 | 5 | 22,542 | Mickey Lolich | Mudcat Grant | Ron Nischwitz | Mel Nelson | Fred Gladding | 569 | 523 | 46 |
| 1965-09-01 | @ MIN | 133 | L 2-5 | 73-60 | 5 | 17,951 | Dave Wickersham | Jim Perry | Jim Perry | Dave Wickersham | Al Worthington | 571 | 528 | 43 |
| 1965-09-02 | @ MIN | 134 | W 5-4 | 74-60 | 4 | 14,075 | Joe Sparma | Jim Merritt | Joe Sparma | Jim Merritt | Terry Fox | 576 | 532 | 44 |
| 1965-09-03 | vs WS2 | 135 | W 10-2 | 75-60 | 3 | 10,053 | Hank Aguirre | Buster Narum | Hank Aguirre | Buster Narum | | 586 | 534 | 52 |
| 1965-09-04 | vs WS2 | 136 | L 0-1 | 75-61 | 4 | 6,643 | Dave Wickersham | Jim Duckworth | Jim Duckworth | Dave Wickersham | Ron Kline | 586 | 535 | 51 |
| 1965-09-05 | vs WS2 | 137 | L 1-2 | 76-62 | 4 | 0 | Mickey Lolich | Pete Richert | Pete Richert | Mickey Lolich | Mike McCormick | 587 | 537 | 50 |
| 1965-09-05 | vs WS2 | 138 | W 11-2 | 76-62 | 4 | 14,209 | Phil Regan | Phil Ortega | Phil Regan | Phil Ortega | | 598 | 539 | 59 |
| 1965-09-06 | vs BOS | 139 | L 1-4 | 76-63 | 5 | 9,864 | Joe Sparma | Earl Wilson | Earl Wilson | Joe Sparma | | 599 | 543 | 56 |
| 1965-09-07 | vs BOS | 140 | W 5-3 | 77-63 | 5 | 5,019 | Julio Navarro | Bill Monbouquette | Terry Fox | Bill Monbouquette | | 604 | 546 | 58 |
| 1965-09-08 | vs BAL | 141 | L 0-2 | 78-64 | 5 | 0 | Hank Aguirre | Steve Barber | Steve Barber | Hank Aguirre | | 604 | 548 | 56 |
| 1965-09-08 | vs BAL | 142 | W 5-0 | 78-64 | 5 | 10,660 | Dave Wickersham | Darold Knowles | Dave Wickersham | Darold Knowles | | 609 | 548 | 61 |
| 1965-09-10 | @ CLE | 143 | W 2-0 | 79-64 | 4 | 6,774 | Mickey Lolich | Sonny Siebert | Mickey Lolich | Sonny Siebert | | 611 | 548 | 63 |
| 1965-09-11 | @ CLE | 144 | W 5-3 | 80-64 | 4 | 3,576 | Joe Sparma | Luis Tiant | Joe Sparma | Luis Tiant | Orlando Pena | 616 | 551 | 65 |
| 1965-09-14 | @ BAL | 145 | L 3-5 | 81-65 | 4 | 0 | Hank Aguirre | Steve Barber | Stu Miller | Orlando Pena | | 619 | 556 | 63 |
| 1965-09-14 | @ BAL | 146 | W 7-1 | 81-65 | 4 | 4,377 | Dave Wickersham | Milt Pappas | Dave Wickersham | Milt Pappas | | 626 | 557 | 69 |
| 1965-09-15 | @ BAL | 147 | L 2-3 | 81-66 | 4 | 3,655 | Denny McLain | Dave McNally | Dave McNally | Denny McLain | | 628 | 560 | 68 |
| 1965-09-17 | @ NYA | 148 | W 4-3 | 82-66 | 4 | 11,162 | Mickey Lolich | Whitey Ford | Mickey Lolich | Whitey Ford | Terry Fox | 632 | 563 | 69 |
| 1965-09-18 | @ NYA | 149 | W 4-3 | 83-66 | 4 | 51,664 | Joe Sparma | Al Downing | Denny McLain | Pete Mikkelsen | | 636 | 566 | 70 |
| 1965-09-19 | @ NYA | 150 | L 0-3 | 83-67 | 4 | 14,283 | Dave Wickersham | Rich Beck | Rich Beck | Dave Wickersham | | 636 | 569 | 67 |
| 1965-09-20 | @ CLE | 151 | L 4-5 | 83-68 | 4 | 1,831 | Hank Aguirre | Luis Tiant | Sam McDowell | Orlando Pena | | 640 | 574 | 66 |
| 1965-09-21 | vs CHA | 152 | W 6-2 | 84-68 | 4 | 6,780 | Denny McLain | Joe Horlen | Denny McLain | Joe Horlen | | 646 | 576 | 70 |
| 1965-09-22 | vs CHA | 153 | L 1-2 | 84-69 | 4 | 5,869 | Mickey Lolich | John Buzhardt | John Buzhardt | Mickey Lolich | Hoyt Wilhelm | 647 | 578 | 69 |
| 1965-09-24 | vs CLE | 154 | L 2-3 | 84-70 | 4 | 12,564 | Joe Sparma | Sam McDowell | Sam McDowell | Orlando Pena | Don McMahon | 649 | 581 | 68 |
| 1965-09-25 | vs CLE | 155 | W 4-1 | 85-70 | 4 | 6,725 | Denny McLain | Jack Kralick | Denny McLain | Jack Kralick | | 653 | 582 | 71 |
| 1965-09-26 | vs CLE | 156 | W 2-0 | 86-71 | 4 | 0 | Mickey Lolich | Ralph Terry | Mickey Lolich | Ralph Terry | | 655 | 582 | 73 |
| 1965-09-26 | vs CLE | 157 | L 1-7 | 86-71 | 4 | 10,986 | Phil Regan | Tom Kelley | Tom Kelley | Phil Regan | | 656 | 589 | 67 |
| 1965-09-28 | @ CHA | 158 | L 3-4 | 87-72 | 4 | 0 | Joe Sparma | Joe Horlen | Hoyt Wilhelm | Terry Fox | | 659 | 593 | 66 |
| 1965-09-28 | @ CHA | 159 | W 4-3 | 87-72 | 4 | 6,123 | Hank Aguirre | John Buzhardt | Hank Aguirre | John Buzhardt | John Hiller | 663 | 596 | 67 |
| 1965-10-02 | @ WS2 | 160 | W 9-1 | 89-72 | 4 | 0 | Denny McLain | Jim Duckworth | Denny McLain | Jim Duckworth | | 672 | 597 | 75 |
| 1965-10-02 | @ WS2 | 161 | W 6-2 | 89-72 | 4 | 1,908 | Mickey Lolich | Pete Richert | Mickey Lolich | Pete Richert | | 678 | 599 | 79 |
| 1965-10-03 | @ WS2 | 162 | L 2-3 | 89-73 | 4 | 3,066 | Joe Sparma | Joe Coleman | Joe Coleman | Joe Sparma | | 680 | 602 | 78 |