| 1965-04-12 | @ MIN | 1 | L 4-5 | 0-1 | 6 | 15,388 | Jim Bouton | Jim Kaat | Jerry Fosnow | Pedro Ramos | | 4 | 5 | -1 |
| 1965-04-14 | @ CAL | 2 | L 3-4 | 0-2 | 9 | 24,637 | Whitey Ford | Dean Chance | George Brunet | Hal Reniff | | 7 | 9 | -2 |
| 1965-04-15 | @ CAL | 3 | W 4-0 | 1-2 | 8 | 17,097 | Mel Stottlemyre | Marcelino Lopez | Mel Stottlemyre | Marcelino Lopez | | 11 | 9 | 2 |
| 1965-04-17 | @ KC1 | 4 | W 5-2 | 2-2 | 5 | 10,589 | Al Downing | Orlando Pena | Al Downing | Orlando Pena | Pedro Ramos | 16 | 11 | 5 |
| 1965-04-18 | @ KC1 | 5 | W 10-4 | 3-2 | 4 | 9,056 | Jim Bouton | Moe Drabowsky | Jim Bouton | Moe Drabowsky | | 26 | 15 | 11 |
| 1965-04-19 | @ KC1 | 6 | L 2-8 | 3-3 | 6 | 6,496 | Whitey Ford | Diego Segui | Diego Segui | Whitey Ford | | 28 | 23 | 5 |
| 1965-04-21 | vs MIN | 7 | L 2-7 | 3-4 | 6 | 38,212 | Mel Stottlemyre | Camilo Pascual | Camilo Pascual | Mel Stottlemyre | Jerry Fosnow | 30 | 30 | 0 |
| 1965-04-22 | vs MIN | 8 | L 2-8 | 3-5 | 8 | 14,046 | Al Downing | Jim Kaat | Jim Kaat | Al Downing | | 32 | 38 | -6 |
| 1965-04-24 | vs CAL | 9 | L 3-6 | 3-6 | 8 | 13,281 | Jim Bouton | Dean Chance | Dean Chance | Jim Bouton | | 35 | 44 | -9 |
| 1965-04-25 | vs CAL | 10 | W 3-2 | 5-6 | 6 | 0 | Whitey Ford | Marcelino Lopez | Whitey Ford | Marcelino Lopez | Pedro Ramos | 38 | 46 | -8 |
| 1965-04-25 | vs CAL | 11 | W 1-0 | 5-6 | 6 | 17,310 | Mel Stottlemyre | Rudy May | Mel Stottlemyre | Rudy May | | 39 | 46 | -7 |
| 1965-04-28 | vs KC1 | 12 | W 5-1 | 6-6 | 6 | 3,001 | Al Downing | Diego Segui | Al Downing | Diego Segui | | 44 | 47 | -3 |
| 1965-04-30 | vs BAL | 13 | L 4-10 | 6-7 | 7 | 17,485 | Jim Bouton | Steve Barber | Steve Barber | Jim Bouton | Dick Hall | 48 | 57 | -9 |
| 1965-05-01 | vs BAL | 14 | W 9-4 | 7-7 | 6 | 11,948 | Whitey Ford | Don Larsen | Whitey Ford | Don Larsen | | 57 | 61 | -4 |
| 1965-05-02 | vs BAL | 15 | L 2-4 | 7-9 | 8 | 0 | Mel Stottlemyre | Dave McNally | Stu Miller | Hal Reniff | | 59 | 65 | -6 |
| 1965-05-02 | vs BAL | 16 | L 0-5 | 7-9 | 8 | 30,009 | Al Downing | Robin Roberts | Robin Roberts | Al Downing | | 59 | 70 | -11 |
| 1965-05-04 | @ CLE | 17 | W 5-3 | 8-9 | 7 | 9,040 | Jim Bouton | Sonny Siebert | Jim Bouton | Sonny Siebert | Pedro Ramos | 64 | 73 | -9 |
| 1965-05-05 | @ CLE | 18 | L 0-4 | 8-10 | 7 | 10,737 | Whitey Ford | Ralph Terry | Ralph Terry | Whitey Ford | | 64 | 77 | -13 |
| 1965-05-07 | @ WS2 | 19 | L 3-4 | 8-12 | 9 | 0 | Mel Stottlemyre | Mike McCormick | Mike McCormick | Mel Stottlemyre | Ron Kline | 67 | 81 | -14 |
| 1965-05-07 | @ WS2 | 20 | L 3-7 | 8-12 | 9 | 24,171 | Al Downing | Dallas Green | Steve Ridzik | Al Downing | Ron Kline | 70 | 88 | -18 |
| 1965-05-08 | @ WS2 | 21 | W 7-3 | 9-12 | 8 | 6,866 | Jim Bouton | Pete Richert | Jim Bouton | Pete Richert | | 77 | 91 | -14 |
| 1965-05-09 | @ WS2 | 22 | L 4-5 | 9-13 | 8 | 23,545 | Whitey Ford | Phil Ortega | Phil Ortega | Whitey Ford | Bennie Daniels | 81 | 96 | -15 |
| 1965-05-10 | @ BOS | 23 | L 2-3 | 9-14 | 9 | 11,163 | Bill Stafford | Jim Lonborg | Jim Lonborg | Bill Stafford | Dick Radatz | 83 | 99 | -16 |
| 1965-05-11 | @ BOS | 24 | W 5-3 | 10-14 | 7 | 15,444 | Mel Stottlemyre | Earl Wilson | Mel Stottlemyre | Earl Wilson | | 88 | 102 | -14 |
| 1965-05-12 | @ BOS | 25 | L 0-2 | 10-15 | 8 | 16,593 | Jim Bouton | Bill Monbouquette | Bill Monbouquette | Jim Bouton | | 88 | 104 | -16 |
| 1965-05-13 | @ BOS | 26 | L 1-4 | 10-16 | 8 | 14,261 | Whitey Ford | Dave Morehead | Dave Morehead | Whitey Ford | | 89 | 108 | -19 |
| 1965-05-14 | @ BAL | 27 | W 9-3 | 11-16 | 8 | 24,211 | Bill Stafford | Robin Roberts | Bill Stafford | Robin Roberts | Steve Hamilton | 98 | 111 | -13 |
| 1965-05-15 | @ BAL | 28 | W 3-2 | 12-16 | 7 | 32,338 | Mel Stottlemyre | Steve Barber | Pedro Ramos | Dick Hall | Hal Reniff | 101 | 113 | -12 |
| 1965-05-16 | @ BAL | 29 | L 5-7 | 12-17 | 8 | 25,740 | Jim Bouton | Dave McNally | Jim Palmer | Pete Mikkelsen | Stu Miller | 106 | 120 | -14 |
| 1965-05-17 | @ BAL | 30 | L 2-9 | 12-18 | 8 | 18,601 | Whitey Ford | Milt Pappas | Milt Pappas | Whitey Ford | | 108 | 129 | -21 |
| 1965-05-18 | vs BOS | 31 | W 4-3 | 13-18 | 8 | 12,371 | Bill Stafford | Dave Morehead | Pedro Ramos | Dick Radatz | | 112 | 132 | -20 |
| 1965-05-19 | vs BOS | 32 | L 0-3 | 13-19 | 8 | 10,352 | Al Downing | Jim Lonborg | Jim Lonborg | Al Downing | | 112 | 135 | -23 |
| 1965-05-20 | vs BOS | 33 | W 6-3 | 14-19 | 8 | 14,356 | Mel Stottlemyre | Bill Monbouquette | Mel Stottlemyre | Bill Monbouquette | Pedro Ramos | 118 | 138 | -20 |
| 1965-05-21 | vs WS2 | 34 | L 4-5 | 14-20 | 8 | 12,190 | Jim Bouton | Mike McCormick | Bennie Daniels | Jim Bouton | Ron Kline | 122 | 143 | -21 |
| 1965-05-22 | vs WS2 | 35 | W 6-0 | 15-20 | 8 | 9,097 | Whitey Ford | Pete Richert | Whitey Ford | Pete Richert | | 128 | 143 | -15 |
| 1965-05-23 | vs WS2 | 36 | L 3-7 | 16-21 | 8 | 0 | Bill Stafford | Phil Ortega | Phil Ortega | Bill Stafford | Ron Kline | 131 | 150 | -19 |
| 1965-05-23 | vs WS2 | 37 | W 3-2 | 16-21 | 8 | 20,840 | Al Downing | Buster Narum | Al Downing | Buster Narum | Pedro Ramos | 134 | 152 | -18 |
| 1965-05-24 | vs CLE | 38 | W 15-5 | 17-21 | 8 | 9,973 | Mel Stottlemyre | Jack Kralick | Mel Stottlemyre | Jack Kralick | | 149 | 157 | -8 |
| 1965-05-25 | vs CLE | 39 | L 1-5 | 17-22 | 8 | 4,925 | Jim Bouton | Sonny Siebert | Sonny Siebert | Jim Bouton | Sam McDowell | 150 | 162 | -12 |
| 1965-05-27 | @ DET | 40 | L 1-4 | 17-23 | 8 | 18,257 | Whitey Ford | Joe Sparma | Joe Sparma | Whitey Ford | | 151 | 166 | -15 |
| 1965-05-28 | @ CHA | 41 | L 0-2 | 17-24 | 8 | 29,677 | Bill Stafford | Joe Horlen | Joe Horlen | Bill Stafford | | 151 | 168 | -17 |
| 1965-05-29 | @ CHA | 42 | L 3-6 | 17-25 | 8 | 17,009 | Al Downing | Tommy John | Tommy John | Al Downing | Eddie Fisher | 154 | 174 | -20 |
| 1965-05-30 | @ CHA | 43 | W 3-2 | 18-25 | 8 | 33,561 | Mel Stottlemyre | Gary Peters | Pete Mikkelsen | Hoyt Wilhelm | | 157 | 176 | -19 |
| 1965-05-31 | vs DET | 44 | W 3-1 | 19-26 | 8 | 0 | Whitey Ford | Denny McLain | Whitey Ford | Denny McLain | Pedro Ramos | 160 | 177 | -17 |
| 1965-05-31 | vs DET | 45 | L 1-5 | 19-26 | 8 | 31,442 | Gil Blanco | Joe Sparma | Joe Sparma | Gil Blanco | | 161 | 182 | -21 |
| 1965-06-04 | vs CHA | 46 | L 0-2 | 19-27 | 9 | 21,350 | Bill Stafford | Joe Horlen | Eddie Fisher | Pete Mikkelsen | | 161 | 184 | -23 |
| 1965-06-05 | vs CHA | 47 | W 4-3 | 20-27 | 9 | 15,722 | Mel Stottlemyre | Gary Peters | Mel Stottlemyre | Eddie Fisher | | 165 | 187 | -22 |
| 1965-06-06 | vs CHA | 48 | W 6-1 | 22-27 | 8 | 0 | Whitey Ford | Tommy John | Whitey Ford | Tommy John | Hal Reniff | 171 | 188 | -17 |
| 1965-06-06 | vs CHA | 49 | W 12-0 | 22-27 | 8 | 33,029 | Al Downing | Juan Pizarro | Al Downing | Juan Pizarro | | 183 | 188 | -5 |
| 1965-06-07 | @ KC1 | 50 | W 4-2 | 23-27 | 8 | 7,815 | Jim Bouton | Fred Talbot | Hal Reniff | Moe Drabowsky | Pedro Ramos | 187 | 190 | -3 |
| 1965-06-08 | @ KC1 | 51 | L 2-3 | 23-28 | 8 | 8,161 | Bill Stafford | John O'Donoghue | John O'Donoghue | Bill Stafford | | 189 | 193 | -4 |
| 1965-06-09 | @ KC1 | 52 | W 5-1 | 24-28 | 8 | 7,111 | Mel Stottlemyre | Diego Segui | Mel Stottlemyre | Diego Segui | | 194 | 194 | 0 |
| 1965-06-11 | @ CAL | 53 | W 6-4 | 25-28 | 7 | 25,036 | Al Downing | George Brunet | Al Downing | George Brunet | | 200 | 198 | 2 |
| 1965-06-12 | @ CAL | 54 | L 3-13 | 25-29 | 7 | 25,795 | Jim Bouton | Rudy May | Rudy May | Jim Bouton | | 203 | 211 | -8 |
| 1965-06-13 | @ CAL | 55 | W 3-0 | 26-29 | 7 | 21,842 | Whitey Ford | Fred Newman | Whitey Ford | Fred Newman | Pedro Ramos | 206 | 211 | -5 |
| 1965-06-14 | @ CLE | 56 | L 4-5 | 26-30 | 7 | 16,421 | Bill Stafford | Ralph Terry | Don McMahon | Pete Mikkelsen | | 210 | 216 | -6 |
| 1965-06-15 | vs BAL | 57 | L 1-2 | 26-31 | 7 | 13,931 | Mel Stottlemyre | Wally Bunker | Stu Miller | Mel Stottlemyre | | 211 | 218 | -7 |
| 1965-06-16 | vs BAL | 58 | L 1-5 | 26-32 | 7 | 10,911 | Al Downing | Dave McNally | Dave McNally | Al Downing | Dick Hall | 212 | 223 | -11 |
| 1965-06-17 | vs BAL | 59 | L 1-2 | 26-33 | 7 | 11,504 | Jim Bouton | Robin Roberts | Dick Hall | Hal Reniff | | 213 | 225 | -12 |
| 1965-06-18 | vs MIN | 60 | W 10-2 | 27-33 | 7 | 22,241 | Bill Stafford | Mel Nelson | Bill Stafford | Mel Nelson | Bobby Tiefenauer | 223 | 227 | -4 |
| 1965-06-19 | vs MIN | 61 | W 5-3 | 28-33 | 7 | 19,919 | Whitey Ford | Mudcat Grant | Whitey Ford | Mudcat Grant | Pedro Ramos | 228 | 230 | -2 |
| 1965-06-20 | vs MIN | 62 | L 4-6 | 28-35 | 7 | 0 | Mel Stottlemyre | Camilo Pascual | Al Worthington | Bobby Tiefenauer | Jim Kaat | 232 | 236 | -4 |
| 1965-06-20 | vs MIN | 63 | L 4-7 | 28-35 | 7 | 71,245 | Al Downing | Dave Boswell | Dave Boswell | Al Downing | Dick Stigman | 236 | 243 | -7 |
| 1965-06-22 | vs KC1 | 64 | L 2-6 | 29-36 | 7 | 0 | Jim Bouton | John O'Donoghue | John O'Donoghue | Jim Bouton | Don Mossi | 238 | 249 | -11 |
| 1965-06-22 | vs KC1 | 65 | W 4-2 | 29-36 | 7 | 13,129 | Bill Stafford | Fred Talbot | Pedro Ramos | Wes Stock | Bobby Tiefenauer | 242 | 251 | -9 |
| 1965-06-23 | vs KC1 | 66 | W 8-3 | 30-36 | 7 | 10,464 | Whitey Ford | Diego Segui | Whitey Ford | Diego Segui | Steve Hamilton | 250 | 254 | -4 |
| 1965-06-24 | vs KC1 | 67 | L 2-6 | 30-37 | 7 | 6,191 | Mel Stottlemyre | Rollie Sheldon | Rollie Sheldon | Mel Stottlemyre | | 252 | 260 | -8 |
| 1965-06-25 | vs CAL | 68 | W 5-1 | 31-37 | 6 | 13,286 | Al Downing | Dean Chance | Al Downing | Bob Lee | Pedro Ramos | 257 | 261 | -4 |
| 1965-06-26 | vs CAL | 69 | W 10-3 | 32-37 | 6 | 13,256 | Jim Bouton | Marcelino Lopez | Bobby Tiefenauer | Marcelino Lopez | Hal Reniff | 267 | 264 | 3 |
| 1965-06-27 | vs CAL | 70 | W 7-2 | 33-37 | 6 | 19,148 | Whitey Ford | George Brunet | Whitey Ford | George Brunet | Pedro Ramos | 274 | 266 | 8 |
| 1965-06-28 | @ WS2 | 71 | W 3-0 | 35-37 | 6 | 0 | Mel Stottlemyre | Pete Richert | Mel Stottlemyre | Pete Richert | | 277 | 266 | 11 |
| 1965-06-28 | @ WS2 | 72 | W 4-3 | 35-37 | 6 | 30,019 | Bill Stafford | Mike McCormick | Bill Stafford | Mike McCormick | Pedro Ramos | 281 | 269 | 12 |
| 1965-06-29 | @ WS2 | 73 | L 1-2 | 35-38 | 6 | 19,637 | Al Downing | Buster Narum | Buster Narum | Al Downing | | 282 | 271 | 11 |
| 1965-06-30 | @ BAL | 74 | W 5-4 | 36-38 | 6 | 18,519 | Jim Bouton | Dave McNally | Jim Bouton | Dave McNally | Pedro Ramos | 287 | 275 | 12 |
| 1965-07-01 | @ BAL | 75 | L 3-4 | 36-39 | 6 | 17,744 | Whitey Ford | Steve Barber | Steve Barber | Whitey Ford | Stu Miller | 290 | 279 | 11 |
| 1965-07-02 | @ BOS | 76 | W 16-2 | 37-39 | 6 | 20,876 | Mel Stottlemyre | Dave Morehead | Mel Stottlemyre | Dave Morehead | | 306 | 281 | 25 |
| 1965-07-03 | @ BOS | 77 | W 6-2 | 38-39 | 6 | 8,690 | Al Downing | Jim Lonborg | Al Downing | Jim Lonborg | Pedro Ramos | 312 | 283 | 29 |
| 1965-07-04 | @ BOS | 78 | L 3-5 | 38-40 | 6 | 17,291 | Jim Bouton | Bill Monbouquette | Bill Monbouquette | Jim Bouton | Dick Radatz | 315 | 288 | 27 |
| 1965-07-05 | @ DET | 79 | W 7-2 | 39-41 | 6 | 0 | Whitey Ford | Mickey Lolich | Whitey Ford | Mickey Lolich | | 322 | 290 | 32 |
| 1965-07-05 | @ DET | 80 | L 4-5 | 39-41 | 6 | 40,153 | Steve Hamilton | Joe Sparma | Joe Sparma | Hal Reniff | Orlando Pena | 326 | 295 | 31 |
| 1965-07-06 | @ DET | 81 | L 0-8 | 39-42 | 6 | 22,052 | Mel Stottlemyre | Denny McLain | Denny McLain | Mel Stottlemyre | | 326 | 303 | 23 |
| 1965-07-07 | @ DET | 82 | W 4-3 | 40-42 | 6 | 23,789 | Al Downing | Hank Aguirre | Al Downing | Hank Aguirre | | 330 | 306 | 24 |
| 1965-07-08 | @ DET | 83 | L 1-6 | 40-43 | 6 | 24,559 | Pete Mikkelsen | Mickey Lolich | Mickey Lolich | Pete Mikkelsen | | 331 | 312 | 19 |
| 1965-07-09 | @ MIN | 84 | L 3-8 | 40-44 | 6 | 30,373 | Jim Bouton | Dave Boswell | Dave Boswell | Jim Bouton | | 334 | 320 | 14 |
| 1965-07-10 | @ MIN | 85 | L 1-4 | 41-45 | 6 | 36,484 | Whitey Ford | Jim Perry | Jim Perry | Whitey Ford | Al Worthington | 335 | 324 | 11 |
| 1965-07-10 | @ MIN | 86 | W 8-6 | 41-45 | 6 | 36,084 | Mel Stottlemyre | Mudcat Grant | Pete Mikkelsen | Dick Stigman | Steve Hamilton | 343 | 330 | 13 |
| 1965-07-11 | @ MIN | 87 | L 5-6 | 41-46 | 7 | 35,263 | Al Downing | Jim Kaat | Jerry Fosnow | Pete Mikkelsen | | 348 | 336 | 12 |
| 1965-07-15 | vs WS2 | 88 | W 2-1 | 42-46 | 6 | 15,964 | Mel Stottlemyre | Phil Ortega | Pete Mikkelsen | Howie Koplitz | | 350 | 337 | 13 |
| 1965-07-16 | vs WS2 | 89 | W 9-5 | 43-46 | 6 | 16,026 | Al Downing | Pete Richert | Al Downing | Pete Richert | Pedro Ramos | 359 | 342 | 17 |
| 1965-07-17 | vs WS2 | 90 | W 5-4 | 44-46 | 6 | 20,196 | Whitey Ford | Buster Narum | Gil Blanco | Ron Kline | | 364 | 346 | 18 |
| 1965-07-18 | vs WS2 | 91 | L 0-3 | 44-47 | 6 | 13,119 | Pete Mikkelsen | Mike McCormick | Mike McCormick | Pete Mikkelsen | | 364 | 349 | 15 |
| 1965-07-19 | vs BOS | 92 | L 1-3 | 44-48 | 6 | 15,340 | Jim Bouton | Jim Lonborg | Jim Lonborg | Jim Bouton | | 365 | 352 | 13 |
| 1965-07-20 | vs BOS | 93 | W 6-3 | 45-48 | 6 | 24,594 | Mel Stottlemyre | Bill Monbouquette | Mel Stottlemyre | Bill Monbouquette | | 371 | 355 | 16 |
| 1965-07-21 | vs CHA | 94 | W 7-6 | 46-48 | 6 | 20,930 | Al Downing | Tommy John | Steve Hamilton | Eddie Fisher | | 378 | 361 | 17 |
| 1965-07-22 | vs CHA | 95 | W 3-1 | 47-48 | 6 | 23,159 | Whitey Ford | Gary Peters | Whitey Ford | Gary Peters | | 381 | 362 | 19 |
| 1965-07-23 | @ CLE | 96 | L 2-5 | 47-49 | 6 | 30,132 | Jim Bouton | Luis Tiant | Luis Tiant | Jim Bouton | Don McMahon | 383 | 367 | 16 |
| 1965-07-24 | @ CLE | 97 | L 0-3 | 47-50 | 6 | 48,777 | Pete Mikkelsen | Sam McDowell | Sam McDowell | Pete Mikkelsen | | 383 | 370 | 13 |
| 1965-07-25 | @ CLE | 98 | W 3-0 | 48-51 | 6 | 0 | Mel Stottlemyre | Sonny Siebert | Mel Stottlemyre | Sonny Siebert | | 386 | 370 | 16 |
| 1965-07-25 | @ CLE | 99 | L 4-7 | 48-51 | 6 | 56,634 | Al Downing | Lee Stange | Jack Kralick | Al Downing | Don McMahon | 390 | 377 | 13 |
| 1965-07-27 | vs DET | 100 | W 4-3 | 49-52 | 6 | 0 | Whitey Ford | Hank Aguirre | Whitey Ford | Hank Aguirre | Steve Hamilton | 394 | 380 | 14 |
| 1965-07-27 | vs DET | 101 | L 0-3 | 49-52 | 6 | 21,598 | Jim Bouton | Joe Sparma | Joe Sparma | Jim Bouton | Fred Gladding | 394 | 383 | 11 |
| 1965-07-28 | vs DET | 102 | L 3-4 | 49-53 | 6 | 14,474 | Jack Cullen | Dave Wickersham | Dave Wickersham | Steve Hamilton | Terry Fox | 397 | 387 | 10 |
| 1965-07-29 | vs DET | 103 | W 7-3 | 50-53 | 6 | 22,714 | Mel Stottlemyre | Denny McLain | Mel Stottlemyre | Denny McLain | | 404 | 390 | 14 |
| 1965-07-30 | vs CLE | 104 | L 0-5 | 50-54 | 6 | 23,006 | Al Downing | Sonny Siebert | Sonny Siebert | Al Downing | Don McMahon | 404 | 395 | 9 |
| 1965-07-31 | vs CLE | 105 | W 7-6 | 51-54 | 6 | 42,170 | Whitey Ford | Luis Tiant | Hal Reniff | Jack Spring | | 411 | 401 | 10 |
| 1965-08-01 | vs CLE | 106 | W 10-6 | 52-55 | 6 | 0 | Jim Bouton | Ralph Terry | Pedro Ramos | Gary Bell | | 421 | 407 | 14 |
| 1965-08-01 | vs CLE | 107 | L 1-4 | 52-55 | 6 | 34,978 | Jack Cullen | Sam McDowell | Sam McDowell | Jack Cullen | | 422 | 411 | 11 |
| 1965-08-03 | @ CHA | 108 | L 2-3 | 52-56 | 6 | 25,570 | Mel Stottlemyre | John Buzhardt | John Buzhardt | Mel Stottlemyre | Eddie Fisher | 424 | 414 | 10 |
| 1965-08-04 | @ CHA | 109 | W 4-3 | 53-56 | 6 | 36,005 | Al Downing | Juan Pizarro | Pete Mikkelsen | Eddie Fisher | | 428 | 417 | 11 |
| 1965-08-05 | @ CHA | 110 | W 3-0 | 54-56 | 6 | 19,954 | Whitey Ford | Tommy John | Whitey Ford | Tommy John | | 431 | 417 | 14 |
| 1965-08-06 | @ DET | 111 | L 4-5 | 54-57 | 6 | 33,653 | Jack Cullen | Mickey Lolich | Orlando Pena | Pedro Ramos | | 435 | 422 | 13 |
| 1965-08-07 | @ DET | 112 | W 6-5 | 55-57 | 6 | 34,625 | Mel Stottlemyre | Hank Aguirre | Mel Stottlemyre | Hank Aguirre | Whitey Ford | 441 | 427 | 14 |
| 1965-08-08 | @ DET | 113 | W 6-5 | 56-57 | 6 | 23,684 | Al Downing | Denny McLain | Hal Reniff | Orlando Pena | | 447 | 432 | 15 |
| 1965-08-10 | vs MIN | 114 | L 3-7 | 56-58 | 6 | 29,529 | Whitey Ford | Jim Kaat | Jim Kaat | Pete Mikkelsen | Al Worthington | 450 | 439 | 11 |
| 1965-08-11 | vs MIN | 115 | W 5-4 | 57-58 | 6 | 30,205 | Mel Stottlemyre | Mudcat Grant | Mel Stottlemyre | Mudcat Grant | | 455 | 443 | 12 |
| 1965-08-12 | vs MIN | 116 | L 2-8 | 57-59 | 6 | 22,372 | Al Downing | Jim Merritt | Jim Merritt | Al Downing | | 457 | 451 | 6 |
| 1965-08-13 | vs KC1 | 117 | W 3-1 | 58-59 | 6 | 10,764 | Jack Cullen | John O'Donoghue | Jack Cullen | John O'Donoghue | Steve Hamilton | 460 | 452 | 8 |
| 1965-08-14 | vs KC1 | 118 | W 3-2 | 59-59 | 6 | 51,246 | Whitey Ford | Fred Talbot | Pedro Ramos | John Wyatt | | 463 | 454 | 9 |
| 1965-08-15 | vs KC1 | 119 | L 1-4 | 60-60 | 6 | 0 | Mel Stottlemyre | Catfish Hunter | Catfish Hunter | Mel Stottlemyre | | 464 | 458 | 6 |
| 1965-08-15 | vs KC1 | 120 | W 7-3 | 60-60 | 6 | 21,441 | Bill Stafford | Rollie Sheldon | Steve Hamilton | Rollie Sheldon | | 471 | 461 | 10 |
| 1965-08-17 | vs CAL | 121 | W 6-1 | 61-60 | 6 | 14,858 | Al Downing | Fred Newman | Al Downing | Fred Newman | | 477 | 462 | 15 |
| 1965-08-18 | vs CAL | 122 | L 3-7 | 61-61 | 6 | 13,572 | Whitey Ford | Dean Chance | Dean Chance | Pedro Ramos | Bob Lee | 480 | 469 | 11 |
| 1965-08-19 | vs CAL | 123 | W 3-1 | 62-61 | 6 | 21,897 | Mel Stottlemyre | Marcelino Lopez | Mel Stottlemyre | Marcelino Lopez | | 483 | 470 | 13 |
| 1965-08-20 | @ BAL | 124 | W 1-0 | 63-61 | 6 | 21,063 | Jack Cullen | Milt Pappas | Jack Cullen | Milt Pappas | | 484 | 470 | 14 |
| 1965-08-23 | @ MIN | 125 | L 3-4 | 63-62 | 6 | 37,787 | Whitey Ford | Mudcat Grant | Al Worthington | Jim Bouton | | 487 | 474 | 13 |
| 1965-08-24 | @ MIN | 126 | W 2-1 | 64-62 | 6 | 33,772 | Mel Stottlemyre | Jim Perry | Mel Stottlemyre | Jim Perry | | 489 | 475 | 14 |
| 1965-08-25 | @ MIN | 127 | L 4-5 | 64-63 | 6 | 33,966 | Al Downing | Jim Merritt | Jim Merritt | Al Downing | Al Worthington | 493 | 480 | 13 |
| 1965-08-26 | @ MIN | 128 | L 2-9 | 64-64 | 6 | 27,073 | Jack Cullen | Jim Kaat | Jim Kaat | Jack Cullen | | 495 | 489 | 6 |
| 1965-08-27 | @ KC1 | 129 | L 0-1 | 64-65 | 6 | 12,163 | Whitey Ford | John O'Donoghue | John O'Donoghue | Whitey Ford | | 495 | 490 | 5 |
| 1965-08-28 | @ KC1 | 130 | L 0-4 | 64-66 | 6 | 16,792 | Mel Stottlemyre | Rollie Sheldon | Rollie Sheldon | Mel Stottlemyre | | 495 | 494 | 1 |
| 1965-08-29 | @ KC1 | 131 | W 4-3 | 65-66 | 6 | 16,167 | Al Downing | Lew Krausse | Al Downing | Lew Krausse | | 499 | 497 | 2 |
| 1965-08-30 | @ CAL | 132 | W 4-2 | 66-66 | 6 | 9,085 | Jack Cullen | George Brunet | Jack Cullen | George Brunet | | 503 | 499 | 4 |
| 1965-08-31 | @ CAL | 133 | L 0-1 | 66-67 | 6 | 14,499 | Bill Stafford | Dean Chance | Dean Chance | Bill Stafford | | 503 | 500 | 3 |
| 1965-09-01 | @ CAL | 134 | L 6-7 | 66-68 | 6 | 11,411 | Mel Stottlemyre | Jack Sanford | Aubrey Gatewood | Pedro Ramos | | 509 | 507 | 2 |
| 1965-09-02 | @ CAL | 135 | W 8-1 | 67-68 | 6 | 5,198 | Whitey Ford | Marcelino Lopez | Whitey Ford | Marcelino Lopez | | 517 | 508 | 9 |
| 1965-09-03 | vs BOS | 136 | W 9-0 | 68-68 | 6 | 14,224 | Al Downing | Bill Monbouquette | Al Downing | Bill Monbouquette | | 526 | 508 | 18 |
| 1965-09-04 | vs BOS | 137 | L 0-1 | 68-70 | 6 | 0 | Jim Bouton | Dave Morehead | Dave Morehead | Jim Bouton | | 526 | 509 | 17 |
| 1965-09-04 | vs BOS | 138 | L 2-7 | 68-70 | 6 | 20,152 | Jack Cullen | Dennis Bennett | Dennis Bennett | Jack Cullen | Dick Radatz | 528 | 516 | 12 |
| 1965-09-05 | vs BOS | 139 | L 3-4 | 68-71 | 6 | 16,977 | Mel Stottlemyre | Jim Lonborg | Dick Radatz | Pedro Ramos | | 531 | 520 | 11 |
| 1965-09-06 | vs BAL | 140 | L 1-2 | 68-73 | 6 | 0 | Whitey Ford | Milt Pappas | Milt Pappas | Whitey Ford | Dick Hall | 532 | 522 | 10 |
| 1965-09-06 | vs BAL | 141 | L 2-6 | 68-73 | 6 | 23,601 | Bill Stafford | Frank Bertaina | Jim Palmer | Bill Stafford | Stu Miller | 534 | 528 | 6 |
| 1965-09-07 | vs BAL | 142 | L 2-4 | 68-75 | 6 | 0 | Al Downing | Dave McNally | Dave McNally | Al Downing | Stu Miller | 536 | 532 | 4 |
| 1965-09-07 | vs BAL | 143 | L 5-9 | 68-75 | 6 | 9,244 | Jack Cullen | Wally Bunker | Wally Bunker | Jack Cullen | Dick Hall | 541 | 541 | 0 |
| 1965-09-08 | vs WS2 | 144 | W 6-5 | 69-75 | 6 | 7,156 | Jim Bouton | Jim Duckworth | Steve Hamilton | Ron Kline | | 547 | 546 | 1 |
| 1965-09-10 | @ CHA | 145 | W 3-1 | 70-75 | 6 | 20,954 | Mel Stottlemyre | Gary Peters | Mel Stottlemyre | Gary Peters | | 550 | 547 | 3 |
| 1965-09-11 | @ CHA | 146 | W 3-1 | 71-75 | 6 | 18,906 | Whitey Ford | Bruce Howard | Whitey Ford | Bruce Howard | Pedro Ramos | 553 | 548 | 5 |
| 1965-09-12 | @ CHA | 147 | L 1-4 | 71-76 | 6 | 18,202 | Al Downing | Tommy John | Tommy John | Al Downing | Hoyt Wilhelm | 554 | 552 | 2 |
| 1965-09-14 | @ WS2 | 148 | W 3-1 | 72-76 | 6 | 7,240 | Rich Beck | Jim Duckworth | Rich Beck | Jim Duckworth | Pedro Ramos | 557 | 553 | 4 |
| 1965-09-15 | @ WS2 | 149 | W 5-3 | 73-76 | 6 | 6,196 | Mel Stottlemyre | Pete Craig | Mel Stottlemyre | Pete Craig | | 562 | 556 | 6 |
| 1965-09-17 | vs DET | 150 | L 3-4 | 73-77 | 6 | 11,162 | Whitey Ford | Mickey Lolich | Mickey Lolich | Whitey Ford | Terry Fox | 565 | 560 | 5 |
| 1965-09-18 | vs DET | 151 | L 3-4 | 73-78 | 6 | 51,664 | Al Downing | Joe Sparma | Denny McLain | Pete Mikkelsen | | 568 | 564 | 4 |
| 1965-09-19 | vs DET | 152 | W 3-0 | 74-78 | 6 | 14,283 | Rich Beck | Dave Wickersham | Rich Beck | Dave Wickersham | | 571 | 564 | 7 |
| 1965-09-21 | vs CLE | 153 | W 9-4 | 75-78 | 6 | 7,222 | Mel Stottlemyre | Ralph Terry | Mel Stottlemyre | Ralph Terry | | 580 | 568 | 12 |
| 1965-09-22 | vs CLE | 154 | L 3-4 | 75-79 | 6 | 5,541 | Whitey Ford | Tom Kelley | Tom Kelley | Whitey Ford | Sam McDowell | 583 | 572 | 11 |
| 1965-09-23 | vs CLE | 155 | L 1-2 | 75-80 | 6 | 3,004 | Jim Bouton | Sonny Siebert | Sonny Siebert | Jim Bouton | Gary Bell | 584 | 574 | 10 |
| 1965-09-25 | vs CHA | 156 | L 1-3 | 75-82 | 6 | 0 | Bill Stafford | Tommy John | Tommy John | Bill Stafford | | 585 | 577 | 8 |
| 1965-09-25 | vs CHA | 157 | L 0-2 | 75-82 | 6 | 19,331 | Mel Stottlemyre | Gary Peters | Gary Peters | Mel Stottlemyre | Hoyt Wilhelm | 585 | 579 | 6 |
| 1965-09-26 | vs CHA | 158 | L 3-5 | 75-83 | 6 | 10,419 | Whitey Ford | Juan Pizarro | Bruce Howard | Whitey Ford | Eddie Fisher | 588 | 584 | 4 |
| 1965-09-28 | @ CLE | 159 | L 3-6 | 75-84 | 6 | 3,674 | Rich Beck | Sonny Siebert | Sonny Siebert | Rich Beck | Don McMahon | 591 | 590 | 1 |
| 1965-09-29 | @ CLE | 160 | L 3-5 | 75-85 | 6 | 4,150 | Al Downing | Sam McDowell | Sam McDowell | Bill Stafford | | 594 | 595 | -1 |
| 1965-10-02 | @ BOS | 161 | W 6-4 | 76-85 | 6 | 4,300 | Mel Stottlemyre | Dennis Bennett | Mel Stottlemyre | Dennis Bennett | | 600 | 599 | 1 |
| 1965-10-03 | @ BOS | 162 | W 11-5 | 77-85 | 6 | 5,933 | Whitey Ford | Earl Wilson | Whitey Ford | Arnold Earley | Pedro Ramos | 611 | 604 | 7 |