| 1965-04-12 | vs NYA | 1 | W 5-4 | 1-0 | 1 | 15,388 | Jim Kaat | Jim Bouton | Jerry Fosnow | Pedro Ramos | | 5 | 4 | 1 |
| 1965-04-15 | vs DET | 2 | L 4-6 | 1-1 | 3 | 2,382 | Camilo Pascual | Dave Wickersham | Dave Wickersham | Jerry Fosnow | | 9 | 10 | -1 |
| 1965-04-17 | vs CLE | 3 | W 3-0 | 2-1 | 2 | 4,492 | Jim Kaat | Dick Donovan | Jim Kaat | Dick Donovan | | 12 | 10 | 2 |
| 1965-04-18 | vs CLE | 4 | W 6-3 | 3-1 | 2 | 3,273 | Mudcat Grant | Ralph Terry | Dave Boswell | Ralph Terry | Al Worthington | 18 | 13 | 5 |
| 1965-04-21 | @ NYA | 5 | W 7-2 | 4-1 | 1 | 38,212 | Camilo Pascual | Mel Stottlemyre | Camilo Pascual | Mel Stottlemyre | Jerry Fosnow | 25 | 15 | 10 |
| 1965-04-22 | @ NYA | 6 | W 8-2 | 5-1 | 1 | 14,046 | Jim Kaat | Al Downing | Jim Kaat | Al Downing | | 33 | 17 | 16 |
| 1965-04-23 | @ DET | 7 | W 8-6 | 6-1 | 1 | 12,038 | Mudcat Grant | Dave Wickersham | Al Worthington | Julio Navarro | | 41 | 23 | 18 |
| 1965-04-24 | @ DET | 8 | L 4-7 | 6-2 | 1 | 3,596 | Dick Stigman | Phil Regan | Larry Sherry | Jerry Fosnow | | 45 | 30 | 15 |
| 1965-04-27 | @ CLE | 9 | W 11-1 | 7-2 | 1 | 3,827 | Camilo Pascual | Sam McDowell | Camilo Pascual | Sam McDowell | | 56 | 31 | 25 |
| 1965-04-28 | @ CLE | 10 | L 3-9 | 7-3 | 2 | 3,691 | Jim Kaat | Jack Kralick | Sonny Siebert | Jim Kaat | | 59 | 40 | 19 |
| 1965-04-30 | @ CHA | 11 | W 7-0 | 8-3 | 1 | 20,164 | Mudcat Grant | Gary Peters | Mudcat Grant | Gary Peters | | 66 | 40 | 26 |
| 1965-05-01 | @ CHA | 12 | L 1-2 | 8-4 | 3 | 7,728 | Camilo Pascual | Joe Horlen | Joe Horlen | Al Worthington | | 67 | 42 | 25 |
| 1965-05-02 | @ CHA | 13 | W 3-2 | 9-5 | 2 | 0 | Jim Kaat | Tommy John | Bill Pleis | Bob Locker | | 70 | 44 | 26 |
| 1965-05-02 | @ CHA | 14 | L 4-5 | 9-5 | 2 | 42,367 | Dave Boswell | Bruce Howard | Bruce Howard | Dave Boswell | Eddie Fisher | 74 | 49 | 25 |
| 1965-05-04 | vs BAL | 15 | W 7-3 | 10-5 | 2 | 9,818 | Mudcat Grant | Wally Bunker | Mudcat Grant | Wally Bunker | | 81 | 52 | 29 |
| 1965-05-05 | vs BAL | 16 | W 9-2 | 11-5 | 2 | 7,104 | Camilo Pascual | Steve Barber | Camilo Pascual | Steve Barber | | 90 | 54 | 36 |
| 1965-05-06 | vs BAL | 17 | L 1-5 | 11-6 | 2 | 5,556 | Jim Kaat | Robin Roberts | Robin Roberts | Jim Kaat | | 91 | 59 | 32 |
| 1965-05-07 | vs CHA | 18 | L 5-13 | 11-7 | 2 | 8,619 | Dick Stigman | Tommy John | Eddie Fisher | Dave Boswell | | 96 | 72 | 24 |
| 1965-05-08 | vs CHA | 19 | W 4-1 | 12-7 | 2 | 10,521 | Mudcat Grant | Gary Peters | Mudcat Grant | Gary Peters | | 100 | 73 | 27 |
| 1965-05-09 | vs CHA | 20 | W 6-1 | 13-7 | 2 | 17,664 | Camilo Pascual | Bruce Howard | Camilo Pascual | Bruce Howard | | 106 | 74 | 32 |
| 1965-05-10 | vs CHA | 21 | W 4-3 | 14-7 | 1 | 7,111 | Jim Kaat | Joe Horlen | Jim Kaat | Joe Horlen | Mel Nelson | 110 | 77 | 33 |
| 1965-05-11 | vs CAL | 22 | W 3-2 | 15-7 | 1 | 12,506 | Dick Stigman | Dean Chance | Johnny Klippstein | Dean Chance | | 113 | 79 | 34 |
| 1965-05-12 | vs CAL | 23 | W 4-3 | 16-7 | 1 | 10,711 | Mudcat Grant | Rudy May | Al Worthington | Bob Lee | | 117 | 82 | 35 |
| 1965-05-13 | vs CAL | 24 | L 3-4 | 16-8 | 2 | 9,742 | Camilo Pascual | Fred Newman | Bob Lee | Al Worthington | | 120 | 86 | 34 |
| 1965-05-14 | @ KC1 | 25 | W 5-3 | 17-8 | 2 | 6,113 | Jim Kaat | John O'Donoghue | Jerry Fosnow | John O'Donoghue | Bill Pleis | 125 | 89 | 36 |
| 1965-05-15 | @ KC1 | 26 | W 2-0 | 18-8 | 2 | 4,327 | Dave Boswell | Don Buschhorn | Dave Boswell | Don Buschhorn | Mel Nelson | 127 | 89 | 38 |
| 1965-05-16 | @ KC1 | 27 | L 4-7 | 18-10 | 2 | 0 | Mudcat Grant | Diego Segui | John Wyatt | Mel Nelson | | 131 | 96 | 35 |
| 1965-05-16 | @ KC1 | 28 | L 2-4 | 18-10 | 2 | 9,560 | Dick Stigman | Fred Talbot | Moe Drabowsky | Johnny Klippstein | Wes Stock | 133 | 100 | 33 |
| 1965-05-17 | @ CAL | 29 | L 4-5 | 18-11 | 2 | 4,989 | Camilo Pascual | Fred Newman | Bob Lee | Johnny Klippstein | | 137 | 105 | 32 |
| 1965-05-18 | @ CAL | 30 | L 1-3 | 18-12 | 2 | 6,197 | Jim Kaat | Marcelino Lopez | Marcelino Lopez | Jim Kaat | George Brunet | 138 | 108 | 30 |
| 1965-05-19 | @ CAL | 31 | W 3-1 | 20-12 | 2 | 0 | Dave Boswell | Dean Chance | Bill Pleis | Don Lee | Dick Stigman | 141 | 109 | 32 |
| 1965-05-19 | @ CAL | 32 | W 3-1 | 20-12 | 2 | 18,902 | Mudcat Grant | Rudy May | Mudcat Grant | Rudy May | Al Worthington | 144 | 110 | 34 |
| 1965-05-21 | vs KC1 | 33 | W 6-4 | 21-12 | 2 | 14,868 | Camilo Pascual | Diego Segui | Camilo Pascual | Moe Drabowsky | Al Worthington | 150 | 114 | 36 |
| 1965-05-22 | vs KC1 | 34 | L 2-6 | 21-13 | 2 | 9,261 | Jim Kaat | Fred Talbot | Fred Talbot | Jim Kaat | John Wyatt | 152 | 120 | 32 |
| 1965-05-25 | @ BOS | 35 | W 17-5 | 22-13 | 2 | 9,523 | Mudcat Grant | Bill Monbouquette | Mudcat Grant | Bill Monbouquette | | 169 | 125 | 44 |
| 1965-05-26 | @ BOS | 36 | W 9-7 | 23-13 | 1 | 9,073 | Camilo Pascual | Earl Wilson | Jim Perry | Earl Wilson | Al Worthington | 178 | 132 | 46 |
| 1965-05-27 | @ BOS | 37 | L 0-2 | 23-14 | 2 | 3,124 | Jim Kaat | Dave Morehead | Dave Morehead | Jim Kaat | Dick Radatz | 178 | 134 | 44 |
| 1965-05-28 | @ WS2 | 38 | W 4-1 | 24-14 | 2 | 15,612 | Dave Boswell | Phil Ortega | Dave Boswell | Phil Ortega | Bill Pleis | 182 | 135 | 47 |
| 1965-05-29 | @ WS2 | 39 | W 11-8 | 25-14 | 2 | 3,373 | Mudcat Grant | Bennie Daniels | Jim Perry | Buster Narum | Al Worthington | 193 | 143 | 50 |
| 1965-05-30 | @ WS2 | 40 | W 6-0 | 26-14 | 1 | 9,518 | Camilo Pascual | Mike McCormick | Camilo Pascual | Mike McCormick | | 199 | 143 | 56 |
| 1965-05-31 | @ BAL | 41 | W 6-0 | 27-15 | 1 | 0 | Jim Kaat | Robin Roberts | Jim Kaat | Robin Roberts | | 205 | 143 | 62 |
| 1965-05-31 | @ BAL | 42 | L 4-5 | 27-15 | 1 | 21,289 | Dick Stigman | Jim Palmer | Stu Miller | Johnny Klippstein | | 209 | 148 | 61 |
| 1965-06-02 | vs BOS | 43 | W 6-3 | 28-15 | 1 | 12,297 | Mudcat Grant | Jim Lonborg | Jim Perry | Jim Lonborg | Al Worthington | 215 | 151 | 64 |
| 1965-06-03 | vs BOS | 44 | W 4-3 | 29-15 | 1 | 5,795 | Camilo Pascual | Bill Monbouquette | Camilo Pascual | Bill Monbouquette | Mel Nelson | 219 | 154 | 65 |
| 1965-06-04 | vs WS2 | 45 | W 9-5 | 30-15 | 1 | 12,765 | Jim Kaat | Howie Koplitz | Jim Kaat | Howie Koplitz | Jerry Fosnow | 228 | 159 | 69 |
| 1965-06-06 | vs WS2 | 46 | W 11-2 | 31-15 | 1 | 30,665 | Dave Boswell | Phil Ortega | Bill Pleis | Phil Ortega | | 239 | 161 | 78 |
| 1965-06-07 | vs CLE | 47 | L 1-2 | 31-16 | 1 | 13,567 | Mudcat Grant | Luis Tiant | Luis Tiant | Mudcat Grant | | 240 | 163 | 77 |
| 1965-06-08 | vs CLE | 48 | W 6-2 | 32-16 | 1 | 11,268 | Camilo Pascual | Sonny Siebert | Camilo Pascual | Sonny Siebert | | 246 | 165 | 81 |
| 1965-06-09 | vs CLE | 49 | L 1-2 | 32-17 | 1 | 18,194 | Jim Kaat | Ralph Terry | Ralph Terry | Jim Kaat | Gary Bell | 247 | 167 | 80 |
| 1965-06-10 | vs CLE | 50 | L 1-4 | 32-18 | 1 | 12,798 | Dave Boswell | Sam McDowell | Sam McDowell | Dave Boswell | Gary Bell | 248 | 171 | 77 |
| 1965-06-11 | @ DET | 51 | W 5-4 | 34-18 | 1 | 0 | Mudcat Grant | Joe Sparma | Dick Stigman | Terry Fox | | 253 | 175 | 78 |
| 1965-06-11 | @ DET | 52 | W 5-4 | 34-18 | 1 | 30,716 | Mel Nelson | Mickey Lolich | Jim Perry | Terry Fox | | 258 | 179 | 79 |
| 1965-06-12 | @ DET | 53 | L 5-8 | 34-19 | 1 | 7,493 | Camilo Pascual | Denny McLain | Denny McLain | Jerry Fosnow | Fred Gladding | 263 | 187 | 76 |
| 1965-06-13 | @ DET | 54 | L 4-5 | 34-20 | 1 | 50,383 | Jim Kaat | Hank Aguirre | Hank Aguirre | Jim Kaat | Mickey Lolich | 267 | 192 | 75 |
| 1965-06-15 | @ CHA | 55 | W 4-0 | 35-20 | 1 | 30,769 | Mudcat Grant | Gary Peters | Mudcat Grant | Gary Peters | | 271 | 192 | 79 |
| 1965-06-16 | @ CHA | 56 | L 1-3 | 35-21 | 1 | 25,769 | Camilo Pascual | John Buzhardt | John Buzhardt | Camilo Pascual | Eddie Fisher | 272 | 195 | 77 |
| 1965-06-17 | @ CHA | 57 | W 3-1 | 36-21 | 1 | 10,837 | Jim Kaat | Joe Horlen | Jim Kaat | Joe Horlen | | 275 | 196 | 79 |
| 1965-06-18 | @ NYA | 58 | L 2-10 | 36-22 | 1 | 22,241 | Mel Nelson | Bill Stafford | Bill Stafford | Mel Nelson | Bobby Tiefenauer | 277 | 206 | 71 |
| 1965-06-19 | @ NYA | 59 | L 3-5 | 36-23 | 1 | 19,919 | Mudcat Grant | Whitey Ford | Whitey Ford | Mudcat Grant | Pedro Ramos | 280 | 211 | 69 |
| 1965-06-20 | @ NYA | 60 | W 6-4 | 38-23 | 1 | 0 | Camilo Pascual | Mel Stottlemyre | Al Worthington | Bobby Tiefenauer | Jim Kaat | 286 | 215 | 71 |
| 1965-06-20 | @ NYA | 61 | W 7-4 | 38-23 | 1 | 71,245 | Dave Boswell | Al Downing | Dave Boswell | Al Downing | Dick Stigman | 293 | 219 | 74 |
| 1965-06-22 | @ CLE | 62 | L 4-5 | 38-24 | 1 | 20,425 | Jim Kaat | Luis Tiant | Gary Bell | Al Worthington | | 297 | 224 | 73 |
| 1965-06-23 | @ CLE | 63 | W 6-3 | 39-24 | 1 | 25,553 | Mudcat Grant | Sonny Siebert | Mudcat Grant | Jack Spring | Dick Stigman | 303 | 227 | 76 |
| 1965-06-24 | @ CLE | 64 | L 1-3 | 39-25 | 1 | 14,513 | Camilo Pascual | Ralph Terry | Ralph Terry | Camilo Pascual | Gary Bell | 304 | 230 | 74 |
| 1965-06-25 | vs DET | 65 | W 4-3 | 40-25 | 1 | 26,998 | Dave Boswell | Dave Wickersham | Johnny Klippstein | Dave Wickersham | | 308 | 233 | 75 |
| 1965-06-26 | vs DET | 66 | L 2-5 | 40-26 | 1 | 20,181 | Bill Pleis | Mickey Lolich | Mickey Lolich | Bill Pleis | Terry Fox | 310 | 238 | 72 |
| 1965-06-27 | vs DET | 67 | W 6-4 | 42-26 | 1 | 0 | Mudcat Grant | Joe Sparma | Al Worthington | Fred Gladding | | 316 | 242 | 74 |
| 1965-06-27 | vs DET | 68 | W 6-5 | 42-26 | 1 | 32,146 | Mel Nelson | Hank Aguirre | Bill Pleis | Larry Sherry | | 322 | 247 | 75 |
| 1965-06-28 | vs CHA | 69 | L 4-17 | 42-27 | 3 | 38,405 | Dave Boswell | John Buzhardt | Eddie Fisher | Dave Boswell | | 326 | 264 | 62 |
| 1965-06-29 | vs CHA | 70 | W 7-6 | 43-27 | 2 | 18,580 | Jim Kaat | Joe Horlen | Dick Stigman | Eddie Fisher | | 333 | 270 | 63 |
| 1965-06-30 | @ CAL | 71 | L 0-5 | 43-28 | 2 | 11,284 | Bill Pleis | Fred Newman | Fred Newman | Bill Pleis | | 333 | 275 | 58 |
| 1965-07-02 | @ KC1 | 72 | W 3-1 | 44-28 | 2 | 5,960 | Mudcat Grant | John O'Donoghue | Mudcat Grant | John O'Donoghue | | 336 | 276 | 60 |
| 1965-07-03 | @ KC1 | 73 | W 3-2 | 45-28 | 1 | 32,503 | Jim Kaat | Diego Segui | Al Worthington | Jim Dickson | Dick Stigman | 339 | 278 | 61 |
| 1965-07-04 | @ KC1 | 74 | W 5-2 | 46-28 | 1 | 8,639 | Camilo Pascual | Fred Talbot | Johnny Klippstein | Fred Talbot | | 344 | 280 | 64 |
| 1965-07-05 | vs BOS | 75 | W 6-2 | 48-28 | 1 | 22,443 | Dave Boswell | Earl Wilson | Dave Boswell | Earl Wilson | Al Worthington | 350 | 282 | 68 |
| 1965-07-05 | vs BOS | 76 | W 2-0 | 48-28 | 1 | 15,262 | Jim Perry | Dave Morehead | Jim Perry | Dave Morehead | | 352 | 282 | 70 |
| 1965-07-06 | vs BOS | 77 | W 9-0 | 49-28 | 1 | 11,378 | Mudcat Grant | Jerry Stephenson | Mudcat Grant | Jerry Stephenson | | 361 | 282 | 79 |
| 1965-07-07 | vs BOS | 78 | W 5-2 | 50-28 | 1 | 17,556 | Jim Kaat | Jim Lonborg | Jim Kaat | Jim Lonborg | Al Worthington | 366 | 284 | 82 |
| 1965-07-09 | vs NYA | 79 | W 8-3 | 51-28 | 1 | 30,373 | Dave Boswell | Jim Bouton | Dave Boswell | Jim Bouton | | 374 | 287 | 87 |
| 1965-07-10 | vs NYA | 80 | W 4-1 | 52-29 | 1 | 36,484 | Jim Perry | Whitey Ford | Jim Perry | Whitey Ford | Al Worthington | 378 | 288 | 90 |
| 1965-07-10 | vs NYA | 81 | L 6-8 | 52-29 | 1 | 36,084 | Mudcat Grant | Mel Stottlemyre | Pete Mikkelsen | Dick Stigman | Steve Hamilton | 384 | 296 | 88 |
| 1965-07-11 | vs NYA | 82 | W 6-5 | 53-29 | 1 | 35,263 | Jim Kaat | Al Downing | Jerry Fosnow | Pete Mikkelsen | | 390 | 301 | 89 |
| 1965-07-15 | vs KC1 | 83 | W 11-3 | 54-30 | 1 | 0 | Jim Kaat | Fred Talbot | Jim Kaat | Fred Talbot | Johnny Klippstein | 401 | 304 | 97 |
| 1965-07-15 | vs KC1 | 84 | L 2-3 | 54-30 | 1 | 16,126 | Jim Perry | Rollie Sheldon | Don Mossi | Al Worthington | John Wyatt | 403 | 307 | 96 |
| 1965-07-16 | vs KC1 | 85 | L 2-10 | 54-31 | 1 | 16,122 | Mudcat Grant | Diego Segui | Diego Segui | Mudcat Grant | | 405 | 317 | 88 |
| 1965-07-17 | vs KC1 | 86 | L 4-5 | 54-32 | 1 | 12,733 | Dick Stigman | John O'Donoghue | Don Mossi | Al Worthington | John Wyatt | 409 | 322 | 87 |
| 1965-07-18 | vs CAL | 87 | L 3-5 | 55-33 | 1 | 0 | Jim Kaat | Fred Newman | Fred Newman | Jim Kaat | Bob Lee | 412 | 327 | 85 |
| 1965-07-18 | vs CAL | 88 | W 5-4 | 55-33 | 1 | 29,313 | Mudcat Grant | Ken McBride | Johnny Klippstein | Ed Sukla | Al Worthington | 417 | 331 | 86 |
| 1965-07-19 | vs CAL | 89 | W 5-2 | 56-33 | 1 | 23,321 | Jim Perry | Dean Chance | Jim Perry | Dean Chance | | 422 | 333 | 89 |
| 1965-07-20 | vs CAL | 90 | L 1-9 | 56-34 | 1 | 14,284 | Camilo Pascual | Marcelino Lopez | Marcelino Lopez | Camilo Pascual | | 423 | 342 | 81 |
| 1965-07-21 | @ BOS | 91 | W 8-6 | 58-34 | 1 | 0 | Jim Kaat | Earl Wilson | Jim Kaat | Earl Wilson | Al Worthington | 431 | 348 | 83 |
| 1965-07-21 | @ BOS | 92 | W 11-8 | 58-34 | 1 | 19,761 | Dick Stigman | Bob Heffner | Al Worthington | Dick Radatz | | 442 | 356 | 86 |
| 1965-07-22 | @ BOS | 93 | W 11-5 | 59-34 | 1 | 5,922 | Mudcat Grant | Dave Morehead | Mudcat Grant | Dave Morehead | Al Worthington | 453 | 361 | 92 |
| 1965-07-23 | @ BAL | 94 | L 2-3 | 59-35 | 1 | 23,160 | Jim Perry | Steve Barber | Steve Barber | Jim Perry | | 455 | 364 | 91 |
| 1965-07-24 | @ BAL | 95 | L 1-3 | 59-36 | 1 | 30,163 | Camilo Pascual | Dave McNally | Dick Hall | Bill Pleis | | 456 | 367 | 89 |
| 1965-07-25 | @ BAL | 96 | W 8-5 | 60-36 | 1 | 11,385 | Jim Kaat | John Miller | Al Worthington | Harvey Haddix | Johnny Klippstein | 464 | 372 | 92 |
| 1965-07-26 | @ BAL | 97 | W 8-2 | 61-36 | 1 | 19,467 | Mudcat Grant | Milt Pappas | Mudcat Grant | Milt Pappas | Garry Roggenburk | 472 | 374 | 98 |
| 1965-07-27 | @ WS2 | 98 | L 7-10 | 62-37 | 1 | 0 | Jim Perry | Pete Richert | Pete Richert | Jim Perry | Ron Kline | 479 | 384 | 95 |
| 1965-07-27 | @ WS2 | 99 | W 9-5 | 62-37 | 1 | 23,691 | Jim Kaat | Bennie Daniels | Al Worthington | Bennie Daniels | | 488 | 389 | 99 |
| 1965-07-28 | @ WS2 | 100 | W 8-1 | 63-37 | 1 | 19,279 | Camilo Pascual | Phil Ortega | Garry Roggenburk | Phil Ortega | | 496 | 390 | 106 |
| 1965-07-30 | vs BAL | 101 | W 3-2 | 64-37 | 1 | 36,813 | Mudcat Grant | Dave McNally | Mudcat Grant | Dick Hall | | 499 | 392 | 107 |
| 1965-07-31 | vs BAL | 102 | W 2-1 | 65-37 | 1 | 29,033 | Jim Perry | John Miller | Al Worthington | Stu Miller | | 501 | 393 | 108 |
| 1965-08-01 | vs BAL | 103 | L 6-7 | 65-38 | 1 | 41,021 | Jim Kaat | Milt Pappas | Jim Palmer | Dick Stigman | Harvey Haddix | 507 | 400 | 107 |
| 1965-08-02 | vs BAL | 104 | W 6-5 | 66-38 | 1 | 23,535 | Jim Merritt | Steve Barber | Johnny Klippstein | Jim Palmer | | 513 | 405 | 108 |
| 1965-08-03 | vs WS2 | 105 | W 4-3 | 67-39 | 1 | 0 | Mudcat Grant | Bennie Daniels | Mudcat Grant | Bennie Daniels | Al Worthington | 517 | 408 | 109 |
| 1965-08-03 | vs WS2 | 106 | L 2-4 | 67-39 | 1 | 22,051 | Dwight Siebler | Mike McCormick | Mike McCormick | Mel Nelson | | 519 | 412 | 107 |
| 1965-08-04 | vs WS2 | 107 | W 4-3 | 68-39 | 1 | 15,812 | Jim Perry | Buster Narum | Dick Stigman | Howie Koplitz | | 523 | 415 | 108 |
| 1965-08-05 | vs WS2 | 108 | W 8-5 | 69-39 | 1 | 7,773 | Jim Kaat | Pete Richert | Jim Kaat | Pete Richert | Johnny Klippstein | 531 | 420 | 111 |
| 1965-08-06 | vs BOS | 109 | W 9-3 | 70-39 | 1 | 25,082 | Jim Merritt | Bill Monbouquette | Jim Merritt | Bill Monbouquette | Bill Pleis | 540 | 423 | 117 |
| 1965-08-07 | vs BOS | 110 | W 9-4 | 71-39 | 1 | 16,220 | Mudcat Grant | Earl Wilson | Mudcat Grant | Earl Wilson | | 549 | 427 | 122 |
| 1965-08-08 | vs BOS | 111 | W 8-0 | 72-39 | 1 | 25,853 | Jim Perry | Dave Morehead | Jim Perry | Dave Morehead | | 557 | 427 | 130 |
| 1965-08-10 | @ NYA | 112 | W 7-3 | 73-39 | 1 | 29,529 | Jim Kaat | Whitey Ford | Jim Kaat | Pete Mikkelsen | Al Worthington | 564 | 430 | 134 |
| 1965-08-11 | @ NYA | 113 | L 4-5 | 73-40 | 1 | 30,205 | Mudcat Grant | Mel Stottlemyre | Mel Stottlemyre | Mudcat Grant | | 568 | 435 | 133 |
| 1965-08-12 | @ NYA | 114 | W 8-2 | 74-40 | 1 | 22,372 | Jim Merritt | Al Downing | Jim Merritt | Al Downing | | 576 | 437 | 139 |
| 1965-08-13 | @ CLE | 115 | L 1-3 | 74-41 | 1 | 27,449 | Jim Perry | Sonny Siebert | Lee Stange | Jim Perry | Bobby Tiefenauer | 577 | 440 | 137 |
| 1965-08-14 | @ CLE | 116 | L 1-3 | 74-42 | 1 | 15,909 | Jim Kaat | Sam McDowell | Sam McDowell | Jim Kaat | | 578 | 443 | 135 |
| 1965-08-15 | @ CLE | 117 | W 4-3 | 75-43 | 1 | 0 | Mudcat Grant | Luis Tiant | Mudcat Grant | Luis Tiant | Al Worthington | 582 | 446 | 136 |
| 1965-08-15 | @ CLE | 118 | L 4-6 | 75-43 | 1 | 41,029 | Dick Stigman | Steve Hargan | Jack Kralick | Bill Pleis | | 586 | 452 | 134 |
| 1965-08-17 | @ DET | 119 | L 4-7 | 75-44 | 1 | 33,677 | Jim Merritt | Hank Aguirre | Hank Aguirre | Jim Merritt | Terry Fox | 590 | 459 | 131 |
| 1965-08-19 | @ DET | 120 | W 8-3 | 77-44 | 1 | 0 | Mudcat Grant | Dave Wickersham | Mudcat Grant | Dave Wickersham | | 598 | 462 | 136 |
| 1965-08-19 | @ DET | 121 | W 2-1 | 77-44 | 1 | 36,076 | Jim Kaat | Mickey Lolich | Jim Kaat | Orlando Pena | | 600 | 463 | 137 |
| 1965-08-20 | @ CAL | 122 | L 1-3 | 78-45 | 1 | 0 | Jim Perry | Jack Sanford | Jack Sanford | Jim Perry | Bob Lee | 601 | 466 | 135 |
| 1965-08-20 | @ CAL | 123 | W 3-1 | 78-45 | 1 | 10,232 | Dave Boswell | George Brunet | Johnny Klippstein | George Brunet | | 604 | 467 | 137 |
| 1965-08-21 | @ CAL | 124 | W 4-2 | 79-45 | 1 | 9,181 | Jim Merritt | Fred Newman | Jim Merritt | Fred Newman | Al Worthington | 608 | 469 | 139 |
| 1965-08-22 | @ CAL | 125 | L 1-4 | 79-46 | 1 | 5,401 | Jim Kaat | Dean Chance | Dean Chance | Jim Kaat | | 609 | 473 | 136 |
| 1965-08-23 | vs NYA | 126 | W 4-3 | 80-46 | 1 | 37,787 | Mudcat Grant | Whitey Ford | Al Worthington | Jim Bouton | | 613 | 476 | 137 |
| 1965-08-24 | vs NYA | 127 | L 1-2 | 80-47 | 1 | 33,772 | Jim Perry | Mel Stottlemyre | Mel Stottlemyre | Jim Perry | | 614 | 478 | 136 |
| 1965-08-25 | vs NYA | 128 | W 5-4 | 81-47 | 1 | 33,966 | Jim Merritt | Al Downing | Jim Merritt | Al Downing | Al Worthington | 619 | 482 | 137 |
| 1965-08-26 | vs NYA | 129 | W 9-2 | 82-47 | 1 | 27,073 | Jim Kaat | Jack Cullen | Jim Kaat | Jack Cullen | | 628 | 484 | 144 |
| 1965-08-27 | vs CLE | 130 | W 7-0 | 83-47 | 1 | 36,999 | Mudcat Grant | Sam McDowell | Mudcat Grant | Sam McDowell | | 635 | 484 | 151 |
| 1965-08-28 | vs CLE | 131 | L 5-6 | 83-48 | 1 | 34,255 | Jim Perry | Luis Tiant | Lee Stange | Al Worthington | Gary Bell | 640 | 490 | 150 |
| 1965-08-29 | vs CLE | 132 | L 1-3 | 83-49 | 1 | 31,781 | Jim Merritt | Steve Hargan | Steve Hargan | Jim Merritt | Sam McDowell | 641 | 493 | 148 |
| 1965-08-30 | vs DET | 133 | W 3-2 | 84-49 | 1 | 15,647 | Jim Kaat | Hank Aguirre | Johnny Klippstein | Larry Sherry | | 644 | 495 | 149 |
| 1965-08-31 | vs DET | 134 | L 6-7 | 84-50 | 1 | 22,542 | Mudcat Grant | Mickey Lolich | Ron Nischwitz | Mel Nelson | Fred Gladding | 650 | 502 | 148 |
| 1965-09-01 | vs DET | 135 | W 5-2 | 85-50 | 1 | 17,951 | Jim Perry | Dave Wickersham | Jim Perry | Dave Wickersham | Al Worthington | 655 | 504 | 151 |
| 1965-09-02 | vs DET | 136 | L 4-5 | 85-51 | 1 | 14,075 | Jim Merritt | Joe Sparma | Joe Sparma | Jim Merritt | Terry Fox | 659 | 509 | 150 |
| 1965-09-03 | vs CHA | 137 | W 6-4 | 86-51 | 1 | 28,407 | Jim Kaat | Bruce Howard | Jim Kaat | Bruce Howard | Al Worthington | 665 | 513 | 152 |
| 1965-09-04 | vs CHA | 138 | L 4-5 | 86-52 | 1 | 27,078 | Mudcat Grant | John Buzhardt | John Buzhardt | Mudcat Grant | Hoyt Wilhelm | 669 | 518 | 151 |
| 1965-09-05 | vs CHA | 139 | L 0-2 | 86-53 | 1 | 39,136 | Jim Perry | Joe Horlen | Joe Horlen | Jim Perry | | 669 | 520 | 149 |
| 1965-09-06 | @ KC1 | 140 | W 8-6 | 87-54 | 1 | 0 | Camilo Pascual | John O'Donoghue | Dick Stigman | Diego Segui | Jim Kaat | 677 | 526 | 151 |
| 1965-09-06 | @ KC1 | 141 | L 3-4 | 87-54 | 1 | 10,489 | Jim Merritt | Rollie Sheldon | Catfish Hunter | Al Worthington | | 680 | 530 | 150 |
| 1965-09-08 | @ CHA | 142 | W 3-2 | 88-54 | 1 | 25,202 | Mudcat Grant | John Buzhardt | Mudcat Grant | John Buzhardt | | 683 | 532 | 151 |
| 1965-09-09 | @ CHA | 143 | W 10-4 | 89-54 | 1 | 5,786 | Jim Kaat | Joe Horlen | Jim Kaat | Joe Horlen | Al Worthington | 693 | 536 | 157 |
| 1965-09-10 | @ BOS | 144 | W 8-5 | 90-54 | 1 | 14,636 | Jim Perry | Dave Morehead | Jim Perry | Dave Morehead | Jim Merritt | 701 | 541 | 160 |
| 1965-09-11 | @ BOS | 145 | W 8-4 | 91-54 | 1 | 7,564 | Camilo Pascual | Jim Lonborg | Camilo Pascual | Jim Lonborg | Garry Roggenburk | 709 | 545 | 164 |
| 1965-09-12 | @ BOS | 146 | W 2-0 | 92-54 | 1 | 8,688 | Mudcat Grant | Earl Wilson | Mudcat Grant | Earl Wilson | | 711 | 545 | 166 |
| 1965-09-14 | vs KC1 | 147 | W 4-3 | 93-54 | 1 | 9,751 | Jim Kaat | John O'Donoghue | Jim Kaat | Jack Aker | Jim Merritt | 715 | 548 | 167 |
| 1965-09-15 | vs KC1 | 148 | W 7-5 | 94-54 | 1 | 9,354 | Jim Perry | Catfish Hunter | Johnny Klippstein | John Wyatt | Bill Pleis | 722 | 553 | 169 |
| 1965-09-17 | vs WS2 | 149 | L 1-2 | 94-55 | 1 | 16,315 | Camilo Pascual | Pete Richert | Pete Richert | Jim Merritt | Ron Kline | 723 | 555 | 168 |
| 1965-09-18 | vs WS2 | 150 | W 4-2 | 95-55 | 1 | 11,256 | Jim Kaat | Phil Ortega | Johnny Klippstein | Phil Ortega | | 727 | 557 | 170 |
| 1965-09-19 | vs WS2 | 151 | W 8-1 | 96-55 | 1 | 11,626 | Jim Perry | Frank Kreutzer | Jim Perry | Frank Kreutzer | | 735 | 558 | 177 |
| 1965-09-20 | vs KC1 | 152 | L 2-8 | 96-56 | 1 | 547 | Mudcat Grant | Catfish Hunter | Catfish Hunter | Mudcat Grant | John Wyatt | 737 | 566 | 171 |
| 1965-09-21 | vs BAL | 153 | L 4-6 | 96-57 | 1 | 6,268 | Camilo Pascual | Milt Pappas | Stu Miller | Dave Boswell | Wally Bunker | 741 | 572 | 169 |
| 1965-09-22 | vs BAL | 154 | L 2-5 | 96-58 | 1 | 9,070 | Jim Kaat | Dave McNally | Dave McNally | Jim Kaat | | 743 | 577 | 166 |
| 1965-09-25 | @ WS2 | 155 | W 5-0 | 98-58 | 1 | 0 | Mudcat Grant | Frank Kreutzer | Mudcat Grant | Frank Kreutzer | | 748 | 577 | 171 |
| 1965-09-25 | @ WS2 | 156 | W 5-3 | 98-58 | 1 | 9,373 | Camilo Pascual | Jim Duckworth | Jim Merritt | Mike McCormick | | 753 | 580 | 173 |
| 1965-09-26 | @ WS2 | 157 | W 2-1 | 99-58 | 1 | 8,302 | Jim Kaat | Pete Richert | Jim Kaat | Pete Richert | | 755 | 581 | 174 |
| 1965-09-28 | @ BAL | 158 | L 2-4 | 99-59 | 1 | 5,918 | Jim Perry | Wally Bunker | Wally Bunker | Jim Perry | Stu Miller | 757 | 585 | 172 |
| 1965-09-29 | @ BAL | 159 | W 3-2 | 100-59 | 1 | 6,928 | Mudcat Grant | Steve Barber | Mudcat Grant | Steve Barber | Johnny Klippstein | 760 | 587 | 173 |
| 1965-09-30 | @ BAL | 160 | W 7-6 | 101-59 | 1 | 6,169 | Jim Kaat | Milt Pappas | Jim Kaat | Milt Pappas | Al Worthington | 767 | 593 | 174 |
| 1965-10-02 | vs CAL | 161 | L 4-5 | 101-60 | 1 | 9,303 | Camilo Pascual | George Brunet | Aubrey Gatewood | Mudcat Grant | Bob Lee | 771 | 598 | 173 |
| 1965-10-03 | vs CAL | 162 | W 3-2 | 102-60 | 1 | 16,729 | Jim Kaat | Jim McGlothlin | Jim Perry | Jim McGlothlin | Johnny Klippstein | 774 | 600 | 174 |