| 1965-04-12 | vs DET | 1 | L 2-6 | 0-1 | 4 | 18,109 | Moe Drabowsky | Mickey Lolich | Mickey Lolich | Moe Drabowsky | Larry Sherry | 2 | 6 | -4 |
| 1965-04-13 | vs DET | 2 | L 4-11 | 0-2 | 6 | 2,028 | Diego Segui | Hank Aguirre | Hank Aguirre | Diego Segui | Denny McLain | 6 | 17 | -11 |
| 1965-04-15 | vs CLE | 3 | W 7-3 | 1-2 | 10 | 2,170 | John O'Donoghue | Sam McDowell | John O'Donoghue | Sam McDowell | | 13 | 20 | -7 |
| 1965-04-17 | vs NYA | 4 | L 2-5 | 1-3 | 10 | 10,589 | Orlando Pena | Al Downing | Al Downing | Orlando Pena | Pedro Ramos | 15 | 25 | -10 |
| 1965-04-18 | vs NYA | 5 | L 4-10 | 1-4 | 10 | 9,056 | Moe Drabowsky | Jim Bouton | Jim Bouton | Moe Drabowsky | | 19 | 35 | -16 |
| 1965-04-19 | vs NYA | 6 | W 8-2 | 2-4 | 8 | 6,496 | Diego Segui | Whitey Ford | Diego Segui | Whitey Ford | | 27 | 37 | -10 |
| 1965-04-21 | @ DET | 7 | L 0-1 | 2-5 | 10 | 32,658 | John O'Donoghue | Hank Aguirre | Hank Aguirre | John O'Donoghue | Larry Sherry | 27 | 38 | -11 |
| 1965-04-23 | @ CLE | 8 | L 2-6 | 2-6 | 10 | 9,812 | Orlando Pena | Dick Donovan | Dick Donovan | Orlando Pena | Luis Tiant | 29 | 44 | -15 |
| 1965-04-24 | @ CLE | 9 | L 1-4 | 2-7 | 10 | 4,088 | Moe Drabowsky | Ralph Terry | Ralph Terry | Fred Talbot | Gary Bell | 30 | 48 | -18 |
| 1965-04-28 | @ NYA | 10 | L 1-5 | 2-8 | 10 | 3,001 | Diego Segui | Al Downing | Al Downing | Diego Segui | | 31 | 53 | -22 |
| 1965-04-30 | vs CAL | 11 | L 0-4 | 2-9 | 10 | 6,279 | John O'Donoghue | Marcelino Lopez | Marcelino Lopez | John O'Donoghue | Bob Lee | 31 | 57 | -26 |
| 1965-05-01 | vs CAL | 12 | L 1-3 | 2-10 | 10 | 3,761 | Orlando Pena | Rudy May | Rudy May | Orlando Pena | Bob Lee | 32 | 60 | -28 |
| 1965-05-02 | vs CAL | 13 | L 8-10 | 3-11 | 10 | 0 | Moe Drabowsky | Fred Newman | Barry Latman | Wes Stock | George Brunet | 40 | 70 | -30 |
| 1965-05-02 | vs CAL | 14 | W 9-5 | 3-11 | 10 | 9,171 | Fred Talbot | Ken McBride | Fred Talbot | Ken McBride | Wes Stock | 49 | 75 | -26 |
| 1965-05-03 | vs WS2 | 15 | W 5-3 | 4-11 | 10 | 2,540 | Diego Segui | Pete Richert | Diego Segui | Pete Richert | | 54 | 78 | -24 |
| 1965-05-04 | vs WS2 | 16 | L 2-4 | 4-12 | 10 | 4,206 | John O'Donoghue | Phil Ortega | Phil Ortega | John O'Donoghue | Ron Kline | 56 | 82 | -26 |
| 1965-05-06 | @ CAL | 17 | L 4-5 | 4-13 | 10 | 4,014 | Orlando Pena | Rudy May | Rudy May | Orlando Pena | Bob Lee | 60 | 87 | -27 |
| 1965-05-07 | @ CAL | 18 | L 4-5 | 5-14 | 10 | 0 | Moe Drabowsky | Dean Chance | Dean Chance | Moe Drabowsky | Bob Lee | 64 | 92 | -28 |
| 1965-05-07 | @ CAL | 19 | W 6-3 | 5-14 | 10 | 8,992 | Fred Talbot | Ron Piche | Fred Talbot | Ron Piche | John Wyatt | 70 | 95 | -25 |
| 1965-05-08 | @ CAL | 20 | L 2-3 | 5-15 | 10 | 6,684 | Diego Segui | Marcelino Lopez | Marcelino Lopez | Diego Segui | | 72 | 98 | -26 |
| 1965-05-09 | @ CAL | 21 | L 3-5 | 5-16 | 10 | 9,591 | John O'Donoghue | Fred Newman | Fred Newman | John O'Donoghue | Bob Lee | 75 | 103 | -28 |
| 1965-05-12 | @ CHA | 22 | L 4-7 | 5-18 | 10 | 0 | Fred Talbot | Juan Pizarro | Tommy John | Fred Talbot | | 79 | 110 | -31 |
| 1965-05-12 | @ CHA | 23 | L 4-6 | 5-18 | 10 | 14,777 | Rollie Sheldon | John Buzhardt | Ted Wills | Orlando Pena | Eddie Fisher | 83 | 116 | -33 |
| 1965-05-13 | @ CHA | 24 | L 3-6 | 5-19 | 10 | 2,025 | Diego Segui | Gary Peters | Gary Peters | Diego Segui | Eddie Fisher | 86 | 122 | -36 |
| 1965-05-14 | vs MIN | 25 | L 3-5 | 5-20 | 10 | 6,113 | John O'Donoghue | Jim Kaat | Jerry Fosnow | John O'Donoghue | Bill Pleis | 89 | 127 | -38 |
| 1965-05-15 | vs MIN | 26 | L 0-2 | 5-21 | 10 | 4,327 | Don Buschhorn | Dave Boswell | Dave Boswell | Don Buschhorn | Mel Nelson | 89 | 129 | -40 |
| 1965-05-16 | vs MIN | 27 | W 7-4 | 7-21 | 10 | 0 | Diego Segui | Mudcat Grant | John Wyatt | Mel Nelson | | 96 | 133 | -37 |
| 1965-05-16 | vs MIN | 28 | W 4-2 | 7-21 | 10 | 9,560 | Fred Talbot | Dick Stigman | Moe Drabowsky | Johnny Klippstein | Wes Stock | 100 | 135 | -35 |
| 1965-05-17 | vs CHA | 29 | L 2-13 | 7-22 | 10 | 5,271 | Rollie Sheldon | Gary Peters | Gary Peters | Rollie Sheldon | | 102 | 148 | -46 |
| 1965-05-18 | vs CHA | 30 | L 4-5 | 7-23 | 10 | 3,565 | Orlando Pena | Joe Horlen | Joe Horlen | Orlando Pena | Eddie Fisher | 106 | 153 | -47 |
| 1965-05-19 | vs CHA | 31 | W 7-3 | 8-23 | 10 | 3,678 | John O'Donoghue | Bruce Howard | John O'Donoghue | Bruce Howard | | 113 | 156 | -43 |
| 1965-05-21 | @ MIN | 32 | L 4-6 | 8-24 | 10 | 14,868 | Diego Segui | Camilo Pascual | Camilo Pascual | Moe Drabowsky | Al Worthington | 117 | 162 | -45 |
| 1965-05-22 | @ MIN | 33 | W 6-2 | 9-24 | 10 | 9,261 | Fred Talbot | Jim Kaat | Fred Talbot | Jim Kaat | John Wyatt | 123 | 164 | -41 |
| 1965-05-25 | @ BAL | 34 | L 3-6 | 9-25 | 10 | 5,242 | John O'Donoghue | Milt Pappas | Harvey Haddix | John O'Donoghue | Stu Miller | 126 | 170 | -44 |
| 1965-05-26 | @ BAL | 35 | W 6-3 | 10-25 | 10 | 6,424 | Diego Segui | Robin Roberts | Diego Segui | Robin Roberts | | 132 | 173 | -41 |
| 1965-05-28 | @ BOS | 36 | L 3-9 | 10-26 | 10 | 9,995 | Fred Talbot | Jim Lonborg | Jim Lonborg | Fred Talbot | Dick Radatz | 135 | 182 | -47 |
| 1965-05-30 | @ BOS | 37 | L 2-3 | 10-27 | 10 | 10,024 | Rollie Sheldon | Bill Monbouquette | Dick Radatz | John Wyatt | | 137 | 185 | -48 |
| 1965-05-31 | @ WS2 | 38 | L 2-5 | 10-29 | 10 | 0 | John O'Donoghue | Howie Koplitz | Howie Koplitz | John O'Donoghue | Steve Ridzik | 139 | 190 | -51 |
| 1965-05-31 | @ WS2 | 39 | L 1-5 | 10-29 | 10 | 11,018 | Diego Segui | Pete Richert | Pete Richert | Diego Segui | | 140 | 195 | -55 |
| 1965-06-02 | vs BAL | 40 | L 4-6 | 10-30 | 10 | 4,459 | Fred Talbot | Steve Barber | Steve Barber | Wes Stock | Dick Hall | 144 | 201 | -57 |
| 1965-06-05 | vs BOS | 41 | L 3-5 | 10-31 | 10 | 4,426 | Diego Segui | Earl Wilson | Dick Radatz | Jesse Hickman | | 147 | 206 | -59 |
| 1965-06-06 | vs BOS | 42 | L 4-9 | 11-32 | 10 | 0 | Don Buschhorn | Dave Morehead | Jay Ritchie | Don Mossi | Dick Radatz | 151 | 215 | -64 |
| 1965-06-06 | vs BOS | 43 | W 4-3 | 11-32 | 10 | 13,598 | Rollie Sheldon | Dennis Bennett | Don Mossi | Bob Duliba | | 155 | 218 | -63 |
| 1965-06-07 | vs NYA | 44 | L 2-4 | 11-33 | 10 | 7,815 | Fred Talbot | Jim Bouton | Hal Reniff | Moe Drabowsky | Pedro Ramos | 157 | 222 | -65 |
| 1965-06-08 | vs NYA | 45 | W 3-2 | 12-33 | 10 | 8,161 | John O'Donoghue | Bill Stafford | John O'Donoghue | Bill Stafford | | 160 | 224 | -64 |
| 1965-06-09 | vs NYA | 46 | L 1-5 | 12-34 | 10 | 7,111 | Diego Segui | Mel Stottlemyre | Mel Stottlemyre | Diego Segui | | 161 | 229 | -68 |
| 1965-06-11 | vs CLE | 47 | W 5-2 | 13-34 | 10 | 4,901 | Rollie Sheldon | Jack Kralick | Rollie Sheldon | Jack Kralick | | 166 | 231 | -65 |
| 1965-06-12 | vs CLE | 48 | W 7-0 | 14-34 | 10 | 8,822 | Fred Talbot | Luis Tiant | Fred Talbot | Luis Tiant | | 173 | 231 | -58 |
| 1965-06-13 | vs CLE | 49 | W 8-4 | 15-35 | 10 | 0 | Don Buschhorn | Sonny Siebert | Don Mossi | Gary Bell | | 181 | 235 | -54 |
| 1965-06-13 | vs CLE | 50 | L 2-5 | 15-35 | 10 | 7,179 | John O'Donoghue | Lee Stange | Lee Stange | John O'Donoghue | | 183 | 240 | -57 |
| 1965-06-15 | vs CAL | 51 | W 5-0 | 16-35 | 10 | 4,550 | Diego Segui | Marcelino Lopez | Diego Segui | Marcelino Lopez | | 188 | 240 | -52 |
| 1965-06-16 | vs CAL | 52 | L 1-7 | 16-37 | 10 | 0 | Fred Talbot | George Brunet | George Brunet | Fred Talbot | | 189 | 247 | -58 |
| 1965-06-16 | vs CAL | 53 | L 4-5 | 16-37 | 10 | 7,343 | Rollie Sheldon | Dean Chance | Bob Lee | Rollie Sheldon | | 193 | 252 | -59 |
| 1965-06-18 | @ DET | 54 | L 1-3 | 16-38 | 10 | 12,073 | John O'Donoghue | Hank Aguirre | Hank Aguirre | John O'Donoghue | | 194 | 255 | -61 |
| 1965-06-19 | @ DET | 55 | L 2-8 | 16-39 | 10 | 6,914 | Diego Segui | Denny McLain | Denny McLain | Diego Segui | | 196 | 263 | -67 |
| 1965-06-20 | @ DET | 56 | L 8-12 | 17-40 | 10 | 0 | Catfish Hunter | Mickey Lolich | Joe Sparma | Diego Segui | Fred Gladding | 204 | 275 | -71 |
| 1965-06-20 | @ DET | 57 | W 2-1 | 17-40 | 10 | 20,127 | Rollie Sheldon | Dave Wickersham | Rollie Sheldon | Dave Wickersham | | 206 | 276 | -70 |
| 1965-06-22 | @ NYA | 58 | W 6-2 | 18-41 | 10 | 0 | John O'Donoghue | Jim Bouton | John O'Donoghue | Jim Bouton | Don Mossi | 212 | 278 | -66 |
| 1965-06-22 | @ NYA | 59 | L 2-4 | 18-41 | 10 | 13,129 | Fred Talbot | Bill Stafford | Pedro Ramos | Wes Stock | Bobby Tiefenauer | 214 | 282 | -68 |
| 1965-06-23 | @ NYA | 60 | L 3-8 | 18-42 | 10 | 10,464 | Diego Segui | Whitey Ford | Whitey Ford | Diego Segui | Steve Hamilton | 217 | 290 | -73 |
| 1965-06-24 | @ NYA | 61 | W 6-2 | 19-42 | 10 | 6,191 | Rollie Sheldon | Mel Stottlemyre | Rollie Sheldon | Mel Stottlemyre | | 223 | 292 | -69 |
| 1965-06-25 | @ CLE | 62 | L 0-2 | 19-43 | 10 | 12,073 | Catfish Hunter | Sam McDowell | Sam McDowell | Catfish Hunter | Gary Bell | 223 | 294 | -71 |
| 1965-06-26 | @ CLE | 63 | W 4-2 | 20-43 | 10 | 6,509 | Fred Talbot | Lee Stange | Fred Talbot | Lee Stange | Don Mossi | 227 | 296 | -69 |
| 1965-06-27 | @ CLE | 64 | L 7-10 | 20-45 | 10 | 0 | John O'Donoghue | Luis Tiant | Jack Spring | Jim Dickson | | 234 | 306 | -72 |
| 1965-06-27 | @ CLE | 65 | L 7-11 | 20-45 | 10 | 17,829 | Wes Stock | Floyd Weaver | Sonny Siebert | Don Mossi | | 241 | 317 | -76 |
| 1965-06-30 | vs CHA | 66 | W 2-1 | 22-45 | 10 | 0 | Fred Talbot | Gary Peters | Fred Talbot | Gary Peters | John Wyatt | 243 | 318 | -75 |
| 1965-06-30 | vs CHA | 67 | W 4-3 | 22-45 | 10 | 4,228 | Rollie Sheldon | Bruce Howard | Jim Dickson | John Buzhardt | | 247 | 321 | -74 |
| 1965-07-02 | vs MIN | 68 | L 1-3 | 22-46 | 10 | 5,960 | John O'Donoghue | Mudcat Grant | Mudcat Grant | John O'Donoghue | | 248 | 324 | -76 |
| 1965-07-03 | vs MIN | 69 | L 2-3 | 22-47 | 10 | 32,503 | Diego Segui | Jim Kaat | Al Worthington | Jim Dickson | Dick Stigman | 250 | 327 | -77 |
| 1965-07-04 | vs MIN | 70 | L 2-5 | 22-48 | 10 | 8,639 | Fred Talbot | Camilo Pascual | Johnny Klippstein | Fred Talbot | | 252 | 332 | -80 |
| 1965-07-05 | vs BAL | 71 | L 4-7 | 22-49 | 10 | 6,386 | Rollie Sheldon | Dave McNally | Robin Roberts | Rollie Sheldon | Stu Miller | 256 | 339 | -83 |
| 1965-07-06 | vs BAL | 72 | L 1-4 | 22-50 | 10 | 3,504 | Catfish Hunter | Steve Barber | Steve Barber | Catfish Hunter | Dick Hall | 257 | 343 | -86 |
| 1965-07-07 | vs BAL | 73 | L 0-1 | 22-51 | 10 | 5,116 | John O'Donoghue | John Miller | John Miller | John O'Donoghue | Stu Miller | 257 | 344 | -87 |
| 1965-07-08 | vs BAL | 74 | L 6-10 | 22-52 | 10 | 2,797 | Diego Segui | Wally Bunker | Wally Bunker | Diego Segui | Dick Hall | 263 | 354 | -91 |
| 1965-07-09 | vs DET | 75 | L 5-7 | 22-53 | 10 | 5,772 | Fred Talbot | Joe Sparma | Fred Gladding | John O'Donoghue | Larry Sherry | 268 | 361 | -93 |
| 1965-07-10 | vs DET | 76 | W 4-3 | 23-53 | 10 | 6,080 | Rollie Sheldon | Denny McLain | Don Mossi | Larry Sherry | | 272 | 364 | -92 |
| 1965-07-11 | vs DET | 77 | L 2-4 | 23-54 | 10 | 5,874 | Wes Stock | Hank Aguirre | Hank Aguirre | Wes Stock | | 274 | 368 | -94 |
| 1965-07-15 | @ MIN | 78 | L 3-11 | 24-55 | 10 | 0 | Fred Talbot | Jim Kaat | Jim Kaat | Fred Talbot | Johnny Klippstein | 277 | 379 | -102 |
| 1965-07-15 | @ MIN | 79 | W 3-2 | 24-55 | 10 | 16,126 | Rollie Sheldon | Jim Perry | Don Mossi | Al Worthington | John Wyatt | 280 | 381 | -101 |
| 1965-07-16 | @ MIN | 80 | W 10-2 | 25-55 | 10 | 16,122 | Diego Segui | Mudcat Grant | Diego Segui | Mudcat Grant | | 290 | 383 | -93 |
| 1965-07-17 | @ MIN | 81 | W 5-4 | 26-55 | 10 | 12,733 | John O'Donoghue | Dick Stigman | Don Mossi | Al Worthington | John Wyatt | 295 | 387 | -92 |
| 1965-07-18 | @ CHA | 82 | L 2-3 | 27-56 | 10 | 0 | Catfish Hunter | John Buzhardt | Bob Locker | John Wyatt | | 297 | 390 | -93 |
| 1965-07-18 | @ CHA | 83 | W 7-5 | 27-56 | 10 | 24,518 | Fred Talbot | Gary Peters | Fred Talbot | Gary Peters | John Wyatt | 304 | 395 | -91 |
| 1965-07-19 | @ CHA | 84 | W 6-3 | 28-56 | 10 | 17,671 | Rollie Sheldon | Joe Horlen | Rollie Sheldon | Joe Horlen | Wes Stock | 310 | 398 | -88 |
| 1965-07-21 | @ BAL | 85 | L 0-1 | 28-58 | 10 | 0 | John O'Donoghue | Milt Pappas | Milt Pappas | John O'Donoghue | Dick Hall | 310 | 399 | -89 |
| 1965-07-21 | @ BAL | 86 | L 2-9 | 28-58 | 10 | 10,719 | Diego Segui | John Miller | John Miller | Diego Segui | | 312 | 408 | -96 |
| 1965-07-22 | @ BAL | 87 | W 9-2 | 29-58 | 10 | 5,496 | Fred Talbot | Wally Bunker | Fred Talbot | Wally Bunker | | 321 | 410 | -89 |
| 1965-07-23 | @ WS2 | 88 | L 3-5 | 29-59 | 10 | 6,209 | Catfish Hunter | Mike McCormick | Mike McCormick | Jack Aker | Steve Ridzik | 324 | 415 | -91 |
| 1965-07-24 | @ WS2 | 89 | L 2-9 | 29-60 | 10 | 2,675 | Rollie Sheldon | Phil Ortega | Phil Ortega | Rollie Sheldon | | 326 | 424 | -98 |
| 1965-07-25 | @ WS2 | 90 | L 3-4 | 30-61 | 10 | 0 | Diego Segui | Howie Koplitz | Steve Ridzik | Don Mossi | | 329 | 428 | -99 |
| 1965-07-25 | @ WS2 | 91 | W 5-3 | 30-61 | 10 | 8,519 | John O'Donoghue | Buster Narum | John O'Donoghue | Marshall Bridges | John Wyatt | 334 | 431 | -97 |
| 1965-07-27 | @ BOS | 92 | W 7-3 | 32-61 | 10 | 0 | Fred Talbot | Jerry Stephenson | Fred Talbot | Jerry Stephenson | Jack Aker | 341 | 434 | -93 |
| 1965-07-27 | @ BOS | 93 | W 10-8 | 32-61 | 10 | 6,674 | Catfish Hunter | Jim Lonborg | Catfish Hunter | Jim Lonborg | Don Mossi | 351 | 442 | -91 |
| 1965-07-28 | @ BOS | 94 | L 0-6 | 32-62 | 10 | 5,270 | Rollie Sheldon | Bill Monbouquette | Bill Monbouquette | Rollie Sheldon | | 351 | 448 | -97 |
| 1965-07-29 | @ BOS | 95 | L 4-6 | 32-63 | 10 | 3,850 | Diego Segui | Earl Wilson | Bob Duliba | Don Mossi | Dick Radatz | 355 | 454 | -99 |
| 1965-07-30 | vs WS2 | 96 | L 1-3 | 32-64 | 10 | 5,252 | John O'Donoghue | Mike McCormick | Mike McCormick | John O'Donoghue | | 356 | 457 | -101 |
| 1965-07-31 | vs WS2 | 97 | W 5-4 | 33-64 | 10 | 28,002 | Fred Talbot | Buster Narum | John Wyatt | Ron Kline | | 361 | 461 | -100 |
| 1965-08-01 | vs WS2 | 98 | L 2-3 | 34-65 | 10 | 0 | Rollie Sheldon | Pete Richert | Pete Richert | Rollie Sheldon | | 363 | 464 | -101 |
| 1965-08-01 | vs WS2 | 99 | W 3-2 | 34-65 | 10 | 10,758 | Catfish Hunter | Phil Ortega | Catfish Hunter | Phil Ortega | John Wyatt | 366 | 466 | -100 |
| 1965-08-03 | vs BOS | 100 | L 5-10 | 34-66 | 10 | 5,576 | Diego Segui | Earl Wilson | Earl Wilson | Diego Segui | Dick Radatz | 371 | 476 | -105 |
| 1965-08-04 | vs BOS | 101 | L 1-5 | 34-67 | 10 | 4,886 | John O'Donoghue | Dave Morehead | Dave Morehead | John O'Donoghue | Dick Radatz | 372 | 481 | -109 |
| 1965-08-05 | vs BOS | 102 | W 5-1 | 35-67 | 10 | 2,187 | Fred Talbot | Jim Lonborg | Fred Talbot | Jim Lonborg | John Wyatt | 377 | 482 | -105 |
| 1965-08-06 | vs BAL | 103 | W 9-4 | 36-67 | 10 | 6,201 | Rollie Sheldon | Milt Pappas | Rollie Sheldon | Milt Pappas | Wes Stock | 386 | 486 | -100 |
| 1965-08-07 | vs BAL | 104 | W 7-4 | 37-67 | 10 | 8,123 | Catfish Hunter | Steve Barber | Catfish Hunter | Steve Barber | John Wyatt | 393 | 490 | -97 |
| 1965-08-08 | vs BAL | 105 | L 5-9 | 38-68 | 10 | 0 | Diego Segui | Wally Bunker | Stu Miller | Don Mossi | | 398 | 499 | -101 |
| 1965-08-08 | vs BAL | 106 | W 4-3 | 38-68 | 10 | 14,521 | John O'Donoghue | Dave McNally | John O'Donoghue | Dave McNally | Don Mossi | 402 | 502 | -100 |
| 1965-08-10 | @ DET | 107 | L 0-3 | 38-69 | 10 | 7,529 | Fred Talbot | Dave Wickersham | Dave Wickersham | Fred Talbot | | 402 | 505 | -103 |
| 1965-08-11 | @ DET | 108 | L 2-6 | 38-71 | 10 | 0 | Catfish Hunter | Joe Sparma | Joe Sparma | Catfish Hunter | | 404 | 511 | -107 |
| 1965-08-11 | @ DET | 109 | L 4-5 | 38-71 | 10 | 12,937 | Rollie Sheldon | Mickey Lolich | Fred Gladding | Jack Aker | | 408 | 516 | -108 |
| 1965-08-12 | @ DET | 110 | L 1-11 | 38-72 | 10 | 6,329 | Diego Segui | Hank Aguirre | Hank Aguirre | Diego Segui | | 409 | 527 | -118 |
| 1965-08-13 | @ NYA | 111 | L 1-3 | 38-73 | 10 | 10,764 | John O'Donoghue | Jack Cullen | Jack Cullen | John O'Donoghue | Steve Hamilton | 410 | 530 | -120 |
| 1965-08-14 | @ NYA | 112 | L 2-3 | 38-74 | 10 | 51,246 | Fred Talbot | Whitey Ford | Pedro Ramos | John Wyatt | | 412 | 533 | -121 |
| 1965-08-15 | @ NYA | 113 | W 4-1 | 39-75 | 10 | 0 | Catfish Hunter | Mel Stottlemyre | Catfish Hunter | Mel Stottlemyre | | 416 | 534 | -118 |
| 1965-08-15 | @ NYA | 114 | L 3-7 | 39-75 | 10 | 21,441 | Rollie Sheldon | Bill Stafford | Steve Hamilton | Rollie Sheldon | | 419 | 541 | -122 |
| 1965-08-17 | @ CLE | 115 | W 3-2 | 40-75 | 10 | 7,298 | Lew Krausse | Lee Stange | Lew Krausse | Lee Stange | Don Mossi | 422 | 543 | -121 |
| 1965-08-18 | @ CLE | 116 | W 4-2 | 41-76 | 10 | 0 | John O'Donoghue | Sam McDowell | Jack Aker | Sam McDowell | John Wyatt | 426 | 545 | -119 |
| 1965-08-18 | @ CLE | 117 | L 1-4 | 41-76 | 10 | 11,736 | Fred Talbot | Jack Kralick | Jack Kralick | Fred Talbot | Gary Bell | 427 | 549 | -122 |
| 1965-08-20 | vs CHA | 118 | L 1-3 | 41-77 | 10 | 6,681 | Catfish Hunter | Gary Peters | Gary Peters | Catfish Hunter | Hoyt Wilhelm | 428 | 552 | -124 |
| 1965-08-21 | vs CHA | 119 | L 6-7 | 41-78 | 10 | 26,690 | Rollie Sheldon | Tommy John | Bruce Howard | Lew Krausse | Frank Lary | 434 | 559 | -125 |
| 1965-08-22 | vs CHA | 120 | L 3-8 | 41-80 | 10 | 0 | Fred Talbot | Joe Horlen | Joe Horlen | Fred Talbot | Eddie Fisher | 437 | 567 | -130 |
| 1965-08-22 | vs CHA | 121 | L 1-2 | 41-80 | 10 | 9,310 | John O'Donoghue | John Buzhardt | John Buzhardt | John O'Donoghue | | 438 | 569 | -131 |
| 1965-08-23 | vs DET | 122 | W 4-3 | 42-80 | 10 | 3,414 | Rollie Sheldon | Mickey Lolich | Rollie Sheldon | Julio Navarro | John Wyatt | 442 | 572 | -130 |
| 1965-08-24 | vs DET | 123 | L 2-8 | 42-81 | 10 | 4,437 | Lew Krausse | Denny McLain | Denny McLain | Lew Krausse | | 444 | 580 | -136 |
| 1965-08-25 | vs DET | 124 | W 5-0 | 43-81 | 10 | 4,794 | Catfish Hunter | Joe Sparma | Catfish Hunter | Joe Sparma | | 449 | 580 | -131 |
| 1965-08-26 | vs DET | 125 | W 5-3 | 44-81 | 10 | 3,806 | Fred Talbot | Hank Aguirre | Jim Dickson | Larry Sherry | John Wyatt | 454 | 583 | -129 |
| 1965-08-27 | vs NYA | 126 | W 1-0 | 45-81 | 10 | 12,163 | John O'Donoghue | Whitey Ford | John O'Donoghue | Whitey Ford | | 455 | 583 | -128 |
| 1965-08-28 | vs NYA | 127 | W 4-0 | 46-81 | 10 | 16,792 | Rollie Sheldon | Mel Stottlemyre | Rollie Sheldon | Mel Stottlemyre | | 459 | 583 | -124 |
| 1965-08-29 | vs NYA | 128 | L 3-4 | 46-82 | 10 | 16,167 | Lew Krausse | Al Downing | Al Downing | Lew Krausse | | 462 | 587 | -125 |
| 1965-08-31 | vs CLE | 129 | L 1-8 | 47-83 | 10 | 0 | Catfish Hunter | Sam McDowell | Sam McDowell | Catfish Hunter | | 463 | 595 | -132 |
| 1965-08-31 | vs CLE | 130 | W 3-2 | 47-83 | 10 | 3,970 | Fred Talbot | Sonny Siebert | Jim Dickson | Bobby Tiefenauer | | 466 | 597 | -131 |
| 1965-09-01 | vs CLE | 131 | W 4-3 | 48-83 | 10 | 3,466 | John O'Donoghue | Luis Tiant | John O'Donoghue | Luis Tiant | Jack Aker | 470 | 600 | -130 |
| 1965-09-02 | vs CLE | 132 | L 6-10 | 48-84 | 10 | 2,113 | Rollie Sheldon | Ralph Terry | Don McMahon | Don Mossi | | 476 | 610 | -134 |
| 1965-09-03 | @ CAL | 133 | W 4-1 | 50-84 | 9 | 0 | Dick Joyce | George Brunet | Jack Aker | George Brunet | John Wyatt | 480 | 611 | -131 |
| 1965-09-03 | @ CAL | 134 | W 1-0 | 50-84 | 9 | 4,319 | Lew Krausse | Fred Newman | Lew Krausse | Fred Newman | John Wyatt | 481 | 611 | -130 |
| 1965-09-04 | @ CAL | 135 | L 1-4 | 50-85 | 10 | 4,418 | Catfish Hunter | Dean Chance | Dean Chance | Catfish Hunter | | 482 | 615 | -133 |
| 1965-09-05 | @ CAL | 136 | L 3-4 | 50-86 | 10 | 2,985 | Fred Talbot | Rudy May | Bob Lee | John Wyatt | | 485 | 619 | -134 |
| 1965-09-06 | vs MIN | 137 | L 6-8 | 51-87 | 10 | 0 | John O'Donoghue | Camilo Pascual | Dick Stigman | Diego Segui | Jim Kaat | 491 | 627 | -136 |
| 1965-09-06 | vs MIN | 138 | W 4-3 | 51-87 | 10 | 10,489 | Rollie Sheldon | Jim Merritt | Catfish Hunter | Al Worthington | | 495 | 630 | -135 |
| 1965-09-08 | vs CAL | 139 | L 3-5 | 51-88 | 10 | 21,576 | Dick Joyce | Dean Chance | Bob Lee | John O'Donoghue | Jim Coates | 498 | 635 | -137 |
| 1965-09-09 | vs CAL | 140 | L 2-7 | 51-89 | 10 | 1,271 | Lew Krausse | Fred Newman | Fred Newman | Lew Krausse | | 500 | 642 | -142 |
| 1965-09-10 | @ BAL | 141 | L 2-5 | 52-90 | 10 | 0 | Fred Talbot | Milt Pappas | Stu Miller | Fred Talbot | | 502 | 647 | -145 |
| 1965-09-10 | @ BAL | 142 | W 10-5 | 52-90 | 10 | 8,838 | Catfish Hunter | John Miller | Jack Aker | Jim Palmer | Don Mossi | 512 | 652 | -140 |
| 1965-09-11 | @ BAL | 143 | W 3-2 | 53-90 | 10 | 3,889 | Rollie Sheldon | Wally Bunker | Rollie Sheldon | Dick Hall | John Wyatt | 515 | 654 | -139 |
| 1965-09-14 | @ MIN | 144 | L 3-4 | 53-91 | 10 | 9,751 | John O'Donoghue | Jim Kaat | Jim Kaat | Jack Aker | Jim Merritt | 518 | 658 | -140 |
| 1965-09-15 | @ MIN | 145 | L 5-7 | 53-92 | 10 | 9,354 | Catfish Hunter | Jim Perry | Johnny Klippstein | John Wyatt | Bill Pleis | 523 | 665 | -142 |
| 1965-09-17 | @ BOS | 146 | W 8-7 | 54-92 | 10 | 3,589 | Rollie Sheldon | Jim Lonborg | Rollie Sheldon | Jim Lonborg | John Wyatt | 531 | 672 | -141 |
| 1965-09-18 | @ BOS | 147 | L 3-5 | 54-93 | 10 | 3,115 | Dick Joyce | Earl Wilson | Earl Wilson | Dick Joyce | Dick Radatz | 534 | 677 | -143 |
| 1965-09-19 | @ BOS | 148 | L 2-3 | 54-94 | 10 | 2,891 | Fred Talbot | Bill Monbouquette | Bill Monbouquette | Fred Talbot | | 536 | 680 | -144 |
| 1965-09-20 | @ MIN | 149 | W 8-2 | 55-94 | 10 | 547 | Catfish Hunter | Mudcat Grant | Catfish Hunter | Mudcat Grant | John Wyatt | 544 | 682 | -138 |
| 1965-09-21 | vs WS2 | 150 | L 3-4 | 55-95 | 10 | 1,600 | Rollie Sheldon | Jim Duckworth | Jim Duckworth | Rollie Sheldon | Ron Kline | 547 | 686 | -139 |
| 1965-09-22 | vs WS2 | 151 | L 2-8 | 55-96 | 10 | 1,731 | Ron Tompkins | Pete Richert | Pete Richert | Paul Lindblad | Steve Ridzik | 549 | 694 | -145 |
| 1965-09-23 | vs WS2 | 152 | W 8-7 | 56-96 | 10 | 690 | Fred Talbot | Mike McCormick | Jack Aker | Ron Kline | | 557 | 701 | -144 |
| 1965-09-24 | vs BOS | 153 | W 8-0 | 57-96 | 10 | 2,304 | Catfish Hunter | Earl Wilson | Catfish Hunter | Earl Wilson | | 565 | 701 | -136 |
| 1965-09-25 | vs BOS | 154 | L 2-5 | 57-97 | 10 | 9,289 | Satchel Paige | Bill Monbouquette | Bill Monbouquette | Don Mossi | | 567 | 706 | -139 |
| 1965-09-26 | vs BOS | 155 | W 2-1 | 58-97 | 10 | 2,874 | Rollie Sheldon | Dennis Bennett | Rollie Sheldon | Dennis Bennett | Jack Aker | 569 | 707 | -138 |
| 1965-09-27 | @ BAL | 156 | L 4-6 | 58-98 | 10 | 703 | Fred Talbot | John Miller | Stu Miller | John Wyatt | | 573 | 713 | -140 |
| 1965-09-28 | @ WS2 | 157 | L 1-6 | 59-99 | 10 | 0 | Catfish Hunter | Joe Coleman | Joe Coleman | Catfish Hunter | | 574 | 719 | -145 |
| 1965-09-28 | @ WS2 | 158 | W 8-6 | 59-99 | 10 | 1,664 | John O'Donoghue | Pete Craig | John O'Donoghue | Pete Craig | Don Mossi | 582 | 725 | -143 |
| 1965-09-29 | @ WS2 | 159 | L 0-9 | 59-100 | 10 | 1,206 | Diego Segui | Jim Hannan | Jim Hannan | Diego Segui | | 582 | 734 | -152 |
| 1965-10-01 | @ CHA | 160 | L 1-6 | 59-101 | 10 | 5,029 | Rollie Sheldon | Tommy John | Tommy John | Don Mossi | | 583 | 740 | -157 |
| 1965-10-02 | @ CHA | 161 | L 0-12 | 59-102 | 10 | 2,104 | Fred Talbot | Bruce Howard | Bruce Howard | Fred Talbot | | 583 | 752 | -169 |
| 1965-10-03 | @ CHA | 162 | L 2-3 | 59-103 | 10 | 4,611 | Catfish Hunter | Joe Horlen | Joe Horlen | Catfish Hunter | Hoyt Wilhelm | 585 | 755 | -170 |