| 1959-04-12 | @ NYA | 1 | L 2-3 | 0-1 | 6 | 22,559 | Tom Brewer | Bob Turley | Bob Turley | Tom Brewer | | 2 | 3 | -1 |
| 1959-04-14 | vs WS1 | 2 | W 7-3 | 1-1 | 4 | 16,467 | Ike Delock | Camilo Pascual | Ike Delock | Camilo Pascual | Murray Wall | 9 | 6 | 3 |
| 1959-04-15 | vs WS1 | 3 | W 7-3 | 2-1 | 4 | 3,498 | Jerry Casale | Russ Kemmerer | Jerry Casale | Russ Kemmerer | | 16 | 9 | 7 |
| 1959-04-16 | vs WS1 | 4 | L 5-7 | 2-2 | 4 | 4,334 | Herb Moford | Pedro Ramos | Pedro Ramos | Herb Moford | | 21 | 16 | 5 |
| 1959-04-17 | vs NYA | 5 | W 4-0 | 3-2 | 3 | 8,878 | Tom Brewer | Bob Turley | Tom Brewer | Bob Turley | | 25 | 16 | 9 |
| 1959-04-18 | vs NYA | 6 | L 7-16 | 3-3 | 5 | 16,882 | Ted Bowsfield | Duke Maas | Duke Maas | Ted Bowsfield | Jim Coates | 32 | 32 | 0 |
| 1959-04-19 | vs NYA | 7 | W 5-4 | 4-3 | 3 | 20,707 | Ike Delock | Johnny Kucks | Leo Kiely | Ryne Duren | | 37 | 36 | 1 |
| 1959-04-21 | vs BAL | 8 | L 2-5 | 4-4 | 5 | 6,358 | Jerry Casale | Hoyt Wilhelm | Hoyt Wilhelm | Jerry Casale | | 39 | 41 | -2 |
| 1959-04-22 | vs BAL | 9 | W 8-4 | 5-4 | 4 | 6,866 | Tom Brewer | Arnie Portocarrero | Murray Wall | Arnie Portocarrero | | 47 | 45 | 2 |
| 1959-04-23 | vs BAL | 10 | L 7-8 | 5-5 | 5 | 7,296 | Ted Bowsfield | Milt Pappas | Ernie Johnson | Leo Kiely | Billy Loes | 54 | 53 | 1 |
| 1959-04-24 | @ WS1 | 11 | W 7-2 | 6-5 | 4 | 7,387 | Ike Delock | Vito Valentinetti | Ike Delock | Vito Valentinetti | | 61 | 55 | 6 |
| 1959-04-25 | @ WS1 | 12 | L 4-8 | 6-6 | 5 | 5,615 | Herb Moford | Pedro Ramos | Pedro Ramos | Herb Moford | | 65 | 63 | 2 |
| 1959-04-26 | @ WS1 | 13 | L 1-2 | 6-7 | 5 | 9,669 | Jerry Casale | Bill Fischer | Bill Fischer | Jerry Casale | | 66 | 65 | 1 |
| 1959-05-01 | @ CHA | 14 | L 0-1 | 6-8 | 7 | 13,022 | Tom Brewer | Early Wynn | Early Wynn | Tom Brewer | | 66 | 66 | 0 |
| 1959-05-02 | @ CHA | 15 | W 5-4 | 7-8 | 6 | 7,718 | Ike Delock | Barry Latman | Ike Delock | Barry Latman | Murray Wall | 71 | 70 | 1 |
| 1959-05-03 | @ KC1 | 16 | L 3-7 | 7-9 | 6 | 12,635 | Frank Sullivan | Ralph Terry | Ralph Terry | Frank Sullivan | | 74 | 77 | -3 |
| 1959-05-04 | @ KC1 | 17 | W 8-4 | 8-9 | 6 | 5,457 | Frank Baumann | John Tsitouris | Bill Monbouquette | Rip Coleman | Murray Wall | 82 | 81 | 1 |
| 1959-05-05 | @ DET | 18 | L 3-8 | 8-10 | 6 | 21,100 | Jerry Casale | Jim Bunning | Jim Bunning | Jerry Casale | | 85 | 89 | -4 |
| 1959-05-06 | @ DET | 19 | W 17-6 | 9-10 | 6 | 4,854 | Tom Brewer | Paul Foytack | Frank Baumann | Paul Foytack | | 102 | 95 | 7 |
| 1959-05-07 | @ DET | 20 | L 1-3 | 9-11 | 6 | 4,215 | Ike Delock | Frank Lary | Frank Lary | Ike Delock | | 103 | 98 | 5 |
| 1959-05-08 | @ BAL | 21 | W 5-0 | 10-11 | 6 | 22,520 | Frank Sullivan | Billy O'Dell | Frank Sullivan | Billy O'Dell | | 108 | 98 | 10 |
| 1959-05-09 | @ BAL | 22 | L 3-4 | 10-12 | 6 | 8,039 | Billy Hoeft | Hoyt Wilhelm | Hoyt Wilhelm | Billy Hoeft | Billy Loes | 111 | 102 | 9 |
| 1959-05-10 | @ BAL | 23 | W 3-2 | 12-12 | 5 | 0 | Tom Brewer | Arnie Portocarrero | Leo Kiely | Jack Harshman | | 114 | 104 | 10 |
| 1959-05-10 | @ BAL | 24 | W 5-1 | 12-12 | 5 | 14,140 | Frank Baumann | Hal Brown | Frank Baumann | Hal Brown | | 119 | 105 | 14 |
| 1959-05-12 | vs CHA | 25 | L 3-4 | 12-13 | 5 | 22,012 | Ike Delock | Dick Donovan | Rudy Arias | Murray Wall | | 122 | 109 | 13 |
| 1959-05-13 | vs CHA | 26 | L 0-4 | 12-14 | 5 | 4,787 | Frank Sullivan | Bob Shaw | Bob Shaw | Frank Sullivan | | 122 | 113 | 9 |
| 1959-05-14 | vs CHA | 27 | L 6-14 | 12-15 | 6 | 3,554 | Billy Hoeft | Early Wynn | Early Wynn | Billy Hoeft | Turk Lown | 128 | 127 | 1 |
| 1959-05-15 | vs CLE | 28 | L 3-4 | 12-16 | 6 | 23,412 | Tom Brewer | Mudcat Grant | Mudcat Grant | Tom Brewer | Jim Perry | 131 | 131 | 0 |
| 1959-05-16 | vs CLE | 29 | L 6-12 | 12-17 | 6 | 16,057 | Frank Baumann | Herb Score | Herb Score | Frank Baumann | | 137 | 143 | -6 |
| 1959-05-17 | vs DET | 30 | W 10-1 | 13-17 | 6 | 17,180 | Ike Delock | Paul Foytack | Ike Delock | Paul Foytack | | 147 | 144 | 3 |
| 1959-05-18 | vs DET | 31 | L 2-14 | 13-18 | 6 | 3,028 | Frank Sullivan | Jim Bunning | Jim Bunning | Frank Sullivan | | 149 | 158 | -9 |
| 1959-05-20 | vs KC1 | 32 | L 2-8 | 13-19 | 6 | 3,256 | Billy Hoeft | Ray Herbert | Ray Herbert | Billy Hoeft | | 151 | 166 | -15 |
| 1959-05-21 | vs KC1 | 33 | W 5-0 | 14-19 | 6 | 2,572 | Tom Brewer | Ned Garver | Tom Brewer | Ned Garver | Leo Kiely | 156 | 166 | -10 |
| 1959-05-22 | vs WS1 | 34 | W 4-3 | 15-19 | 6 | 15,109 | Ike Delock | Camilo Pascual | Ike Delock | Camilo Pascual | | 160 | 169 | -9 |
| 1959-05-23 | vs WS1 | 35 | L 4-10 | 15-20 | 6 | 10,606 | Frank Sullivan | Pedro Ramos | Tex Clevenger | Murray Wall | | 164 | 179 | -15 |
| 1959-05-24 | vs WS1 | 36 | L 3-8 | 15-21 | 6 | 9,484 | Jerry Casale | Bill Fischer | Bill Fischer | Jerry Casale | Chuck Stobbs | 167 | 187 | -20 |
| 1959-05-26 | @ NYA | 37 | W 12-2 | 16-21 | 7 | 33,173 | Tom Brewer | Bob Turley | Tom Brewer | Bob Turley | | 179 | 189 | -10 |
| 1959-05-27 | @ NYA | 38 | L 2-3 | 16-22 | 7 | 9,844 | Ike Delock | Duke Maas | Duke Maas | Ike Delock | Ryne Duren | 181 | 192 | -11 |
| 1959-05-28 | @ WS1 | 39 | W 3-1 | 17-22 | 6 | 10,381 | Frank Sullivan | Pedro Ramos | Frank Sullivan | Pedro Ramos | | 184 | 193 | -9 |
| 1959-05-29 | @ WS1 | 40 | L 6-7 | 17-23 | 7 | 3,030 | Bill Monbouquette | Bill Fischer | Pedro Ramos | Murray Wall | | 190 | 200 | -10 |
| 1959-05-30 | vs BAL | 41 | W 5-4 | 19-23 | 6 | 0 | Tom Brewer | Milt Pappas | Jerry Casale | Billy Loes | Leo Kiely | 195 | 204 | -9 |
| 1959-05-30 | vs BAL | 42 | W 8-3 | 19-23 | 6 | 19,403 | Ted Wills | Jerry Walker | Ted Wills | Jerry Walker | | 203 | 207 | -4 |
| 1959-05-31 | vs BAL | 43 | L 1-2 | 19-24 | 8 | 12,506 | Ike Delock | Hal Brown | Hal Brown | Ike Delock | | 204 | 209 | -5 |
| 1959-06-02 | @ KC1 | 44 | L 3-5 | 19-25 | 8 | 14,047 | Frank Sullivan | Ray Herbert | Tom Sturdivant | Frank Sullivan | Rip Coleman | 207 | 214 | -7 |
| 1959-06-03 | @ KC1 | 45 | L 3-5 | 19-25 | 8 | 12,545 | Bill Monbouquette | Johnny Kucks | Johnny Kucks | Bill Monbouquette | Ray Herbert | 210 | 219 | -9 |
| 1959-06-04 | @ KC1 | 46 | W 5-2 | 20-25 | 8 | 9,210 | Jerry Casale | Rip Coleman | Jerry Casale | Rip Coleman | | 215 | 221 | -6 |
| 1959-06-05 | @ CHA | 47 | L 2-5 | 20-26 | 8 | 32,321 | Frank Baumann | Early Wynn | Gerry Staley | Murray Wall | Rudy Arias | 217 | 226 | -9 |
| 1959-06-06 | @ CHA | 48 | W 4-2 | 21-26 | 8 | 10,301 | Ted Wills | Ray Moore | Ted Wills | Ray Moore | Mike Fornieles | 221 | 228 | -7 |
| 1959-06-07 | @ CHA | 49 | L 4-9 | 22-27 | 7 | 0 | Ike Delock | Dick Donovan | Dick Donovan | Ike Delock | Gerry Staley | 225 | 237 | -12 |
| 1959-06-07 | @ CHA | 50 | W 4-2 | 22-27 | 7 | 25,844 | Frank Sullivan | Billy Pierce | Frank Sullivan | Billy Pierce | Mike Fornieles | 229 | 239 | -10 |
| 1959-06-08 | vs DET | 51 | L 3-6 | 22-28 | 8 | 17,119 | Tom Brewer | Jim Bunning | Jim Bunning | Bill Monbouquette | | 232 | 245 | -13 |
| 1959-06-09 | vs DET | 52 | W 5-2 | 23-28 | 8 | 14,573 | Jerry Casale | Jerry Davie | Jerry Casale | Jerry Davie | | 237 | 247 | -10 |
| 1959-06-10 | vs DET | 53 | L 9-10 | 23-29 | 8 | 4,343 | Ike Delock | Paul Foytack | Tom Morgan | Mike Fornieles | Dave Sisler | 246 | 257 | -11 |
| 1959-06-11 | vs DET | 54 | L 1-8 | 23-30 | 8 | 3,248 | Ted Wills | Ray Narleski | Ray Narleski | Ted Wills | | 247 | 265 | -18 |
| 1959-06-12 | vs KC1 | 55 | L 2-3 | 23-31 | 8 | 13,434 | Frank Sullivan | Rip Coleman | Rip Coleman | Frank Sullivan | Tom Sturdivant | 249 | 268 | -19 |
| 1959-06-13 | vs KC1 | 56 | W 6-1 | 24-31 | 7 | 5,513 | Tom Brewer | Ray Herbert | Tom Brewer | Ray Herbert | | 255 | 269 | -14 |
| 1959-06-14 | vs KC1 | 57 | W 6-1 | 25-31 | 7 | 8,160 | Jerry Casale | Johnny Kucks | Jerry Casale | Johnny Kucks | | 261 | 270 | -9 |
| 1959-06-15 | vs CLE | 58 | L 1-5 | 25-32 | 7 | 12,322 | Bill Monbouquette | Gary Bell | Gary Bell | Bill Monbouquette | | 262 | 275 | -13 |
| 1959-06-16 | vs CLE | 59 | L 1-4 | 25-33 | 7 | 16,656 | Ted Wills | Cal McLish | Cal McLish | Ted Wills | | 263 | 279 | -16 |
| 1959-06-18 | vs CLE | 60 | W 7-6 | 26-33 | 8 | 3,386 | Frank Sullivan | Bobby Locke | Jack Harshman | Mike Garcia | | 270 | 285 | -15 |
| 1959-06-20 | vs CHA | 61 | W 8-2 | 28-33 | 6 | 12,997 | Tom Brewer | Early Wynn | Tom Brewer | Early Wynn | | 278 | 287 | -9 |
| 1959-06-20 | vs CHA | 62 | W 9-0 | 28-33 | 6 | 16,067 | Jerry Casale | Dick Donovan | Jerry Casale | Dick Donovan | | 287 | 287 | 0 |
| 1959-06-21 | vs CHA | 63 | L 2-3 | 28-34 | 6 | 21,094 | Ted Wills | Billy Pierce | Billy Pierce | Ted Wills | | 289 | 290 | -1 |
| 1959-06-23 | @ DET | 64 | W 10-4 | 29-34 | 6 | 40,085 | Ike Delock | Paul Foytack | Ike Delock | Paul Foytack | | 299 | 294 | 5 |
| 1959-06-24 | @ DET | 65 | W 4-2 | 30-34 | 6 | 9,327 | Jack Harshman | Don Mossi | Jack Harshman | Don Mossi | Mike Fornieles | 303 | 296 | 7 |
| 1959-06-25 | @ DET | 66 | L 5-10 | 30-35 | 6 | 10,144 | Tom Brewer | Jim Bunning | Jim Bunning | Tom Brewer | Tom Morgan | 308 | 306 | 2 |
| 1959-06-26 | @ CLE | 67 | L 5-11 | 30-36 | 6 | 25,416 | Jerry Casale | Cal McLish | Cal McLish | Jerry Casale | | 313 | 317 | -4 |
| 1959-06-27 | @ CLE | 68 | W 6-4 | 31-36 | 6 | 10,919 | Frank Sullivan | Mudcat Grant | Frank Sullivan | Mudcat Grant | Tom Brewer | 319 | 321 | -2 |
| 1959-06-28 | @ CLE | 69 | L 4-5 | 31-38 | 7 | 0 | Ike Delock | Gary Bell | Jim Perry | Jack Harshman | | 323 | 326 | -3 |
| 1959-06-28 | @ CLE | 70 | L 0-1 | 31-38 | 7 | 27,610 | Ted Wills | Herb Score | Herb Score | Ted Wills | | 323 | 327 | -4 |
| 1959-06-30 | @ WS1 | 71 | L 1-6 | 31-39 | 7 | 10,214 | Tom Brewer | Pedro Ramos | Pedro Ramos | Tom Brewer | | 324 | 333 | -9 |
| 1959-07-01 | @ WS1 | 72 | L 1-4 | 31-40 | 7 | 9,338 | Jerry Casale | Camilo Pascual | Camilo Pascual | Jerry Casale | | 325 | 337 | -12 |
| 1959-07-02 | @ WS1 | 73 | L 3-6 | 31-41 | 8 | 3,677 | Frank Sullivan | Bill Fischer | Dick Hyde | Leo Kiely | | 328 | 343 | -15 |
| 1959-07-03 | @ BAL | 74 | L 1-6 | 31-42 | 8 | 13,997 | Jack Harshman | Jack Fisher | Billy O'Dell | Jack Harshman | | 329 | 349 | -20 |
| 1959-07-04 | @ BAL | 75 | L 5-11 | 31-43 | 8 | 10,628 | Ted Wills | Milt Pappas | Milt Pappas | Ted Wills | | 334 | 360 | -26 |
| 1959-07-05 | @ BAL | 76 | W 9-0 | 33-43 | 7 | 0 | Tom Brewer | Hal Brown | Tom Brewer | Hal Brown | | 343 | 360 | -17 |
| 1959-07-05 | @ BAL | 77 | W 6-3 | 33-43 | 7 | 16,672 | Frank Baumann | Hoyt Wilhelm | Frank Baumann | Hoyt Wilhelm | Frank Sullivan | 349 | 363 | -14 |
| 1959-07-08 | @ NYA | 78 | L 5-11 | 33-44 | 7 | 25,702 | Ike Delock | Don Larsen | Bobby Shantz | Jack Harshman | | 354 | 374 | -20 |
| 1959-07-09 | vs NYA | 79 | W 14-3 | 34-44 | 8 | 30,253 | Frank Sullivan | Bob Turley | Frank Sullivan | Bob Turley | | 368 | 377 | -9 |
| 1959-07-10 | vs NYA | 80 | W 8-5 | 35-44 | 7 | 25,882 | Tom Brewer | Whitey Ford | Tom Brewer | Whitey Ford | Mike Fornieles | 376 | 382 | -6 |
| 1959-07-11 | vs NYA | 81 | W 8-4 | 36-44 | 7 | 24,232 | Jerry Casale | Duke Maas | Murray Wall | Jim Bronstad | | 384 | 386 | -2 |
| 1959-07-12 | vs NYA | 82 | W 7-3 | 37-44 | 7 | 29,626 | Ike Delock | Ralph Terry | Bill Monbouquette | Ralph Terry | | 391 | 389 | 2 |
| 1959-07-13 | vs NYA | 83 | W 13-3 | 38-44 | 7 | 22,064 | Frank Sullivan | Don Larsen | Frank Sullivan | Don Larsen | | 404 | 392 | 12 |
| 1959-07-14 | vs CHA | 84 | L 3-7 | 38-45 | 7 | 20,606 | Ted Wills | Billy Pierce | Billy Pierce | Ted Wills | Turk Lown | 407 | 399 | 8 |
| 1959-07-16 | vs CHA | 85 | L 3-4 | 39-46 | 7 | 0 | Tom Brewer | Dick Donovan | Dick Donovan | Tom Brewer | Gerry Staley | 410 | 403 | 7 |
| 1959-07-16 | vs CHA | 86 | W 5-4 | 39-46 | 7 | 17,285 | Jerry Casale | Barry Latman | Mike Fornieles | Ray Moore | | 415 | 407 | 8 |
| 1959-07-17 | vs CLE | 87 | L 7-8 | 39-47 | 7 | 26,432 | Ike Delock | Bobby Locke | Bobby Locke | Ike Delock | Gary Bell | 422 | 415 | 7 |
| 1959-07-18 | vs CLE | 88 | L 5-7 | 39-48 | 7 | 14,453 | Frank Sullivan | Herb Score | Mike Garcia | Murray Wall | Cal McLish | 427 | 422 | 5 |
| 1959-07-19 | vs CLE | 89 | W 6-5 | 40-49 | 7 | 0 | Bill Monbouquette | Gary Bell | Leo Kiely | Jim Perry | | 433 | 427 | 6 |
| 1959-07-19 | vs CLE | 90 | L 3-5 | 40-49 | 7 | 27,753 | Frank Baumann | Mudcat Grant | Al Cicotte | Frank Baumann | | 436 | 432 | 4 |
| 1959-07-21 | @ CHA | 91 | L 1-2 | 40-50 | 8 | 28,534 | Tom Brewer | Dick Donovan | Dick Donovan | Tom Brewer | | 437 | 434 | 3 |
| 1959-07-22 | @ CHA | 92 | L 4-5 | 40-51 | 8 | 11,847 | Jerry Casale | Early Wynn | Turk Lown | Leo Kiely | | 441 | 439 | 2 |
| 1959-07-24 | @ KC1 | 93 | L 1-3 | 40-52 | 8 | 12,583 | Frank Sullivan | Johnny Kucks | Johnny Kucks | Frank Sullivan | | 442 | 442 | 0 |
| 1959-07-25 | @ KC1 | 94 | L 0-3 | 40-53 | 8 | 15,897 | Al Schroll | Bud Daley | Bud Daley | Al Schroll | | 442 | 445 | -3 |
| 1959-07-26 | @ KC1 | 95 | L 4-5 | 40-54 | 8 | 14,905 | Tom Brewer | Ray Herbert | Ray Herbert | Ike Delock | Rip Coleman | 446 | 450 | -4 |
| 1959-07-27 | @ CLE | 96 | W 4-0 | 41-54 | 8 | 12,716 | Jerry Casale | Herb Score | Jerry Casale | Herb Score | | 450 | 450 | 0 |
| 1959-07-28 | @ CLE | 97 | L 2-5 | 42-55 | 8 | 0 | Frank Sullivan | Gary Bell | Gary Bell | Frank Sullivan | | 452 | 455 | -3 |
| 1959-07-28 | @ CLE | 98 | W 8-4 | 42-55 | 8 | 29,525 | Bill Monbouquette | Don Ferrarese | Bill Monbouquette | Jim Perry | Mike Fornieles | 460 | 459 | 1 |
| 1959-07-29 | @ CLE | 99 | W 4-1 | 43-55 | 7 | 14,591 | Al Schroll | Cal McLish | Al Schroll | Cal McLish | | 464 | 460 | 4 |
| 1959-07-30 | @ CLE | 100 | L 3-4 | 43-56 | 7 | 10,244 | Tom Brewer | Mudcat Grant | Bobby Locke | Mike Fornieles | | 467 | 464 | 3 |
| 1959-07-31 | @ DET | 101 | W 6-5 | 44-56 | 7 | 31,916 | Earl Wilson | Jim Bunning | Mike Fornieles | Jim Bunning | | 473 | 469 | 4 |
| 1959-08-01 | @ DET | 102 | L 2-6 | 44-57 | 7 | 9,772 | Jerry Casale | Don Mossi | Don Mossi | Jerry Casale | | 475 | 475 | 0 |
| 1959-08-02 | @ DET | 103 | W 5-4 | 45-57 | 7 | 16,722 | Bill Monbouquette | Paul Foytack | Ike Delock | Paul Foytack | | 480 | 479 | 1 |
| 1959-08-04 | vs KC1 | 104 | W 4-1 | 46-58 | 7 | 0 | Tom Brewer | John Tsitouris | Tom Brewer | John Tsitouris | Mike Fornieles | 484 | 480 | 4 |
| 1959-08-04 | vs KC1 | 105 | L 6-8 | 46-58 | 7 | 21,304 | Al Schroll | Rip Coleman | Murry Dickson | Al Schroll | Tom Sturdivant | 490 | 488 | 2 |
| 1959-08-05 | vs KC1 | 106 | W 17-6 | 47-58 | 7 | 15,980 | Earl Wilson | Johnny Kucks | Ike Delock | Howie Reed | Leo Kiely | 507 | 494 | 13 |
| 1959-08-06 | vs KC1 | 107 | W 4-3 | 48-58 | 7 | 7,673 | Jerry Casale | Ray Herbert | Jerry Casale | Ray Herbert | Leo Kiely | 511 | 497 | 14 |
| 1959-08-07 | vs DET | 108 | W 4-3 | 49-58 | 7 | 21,099 | Bill Monbouquette | Jim Bunning | Bill Monbouquette | Ray Narleski | | 515 | 500 | 15 |
| 1959-08-08 | vs DET | 109 | W 4-3 | 50-58 | 7 | 13,930 | Al Schroll | Frank Lary | Ike Delock | Pete Burnside | | 519 | 503 | 16 |
| 1959-08-09 | vs DET | 110 | L 3-7 | 50-59 | 7 | 12,500 | Tom Brewer | Don Mossi | Don Mossi | Tom Brewer | Paul Foytack | 522 | 510 | 12 |
| 1959-08-10 | vs NYA | 111 | L 4-7 | 50-60 | 7 | 32,004 | Frank Sullivan | Don Larsen | Whitey Ford | Al Schroll | | 526 | 517 | 9 |
| 1959-08-11 | vs NYA | 112 | L 5-8 | 50-61 | 7 | 25,032 | Jerry Casale | Duke Maas | Duke Maas | Jerry Casale | Bobby Shantz | 531 | 525 | 6 |
| 1959-08-12 | @ BAL | 113 | W 5-4 | 51-61 | 7 | 12,235 | Bill Monbouquette | Billy Hoeft | Ike Delock | Hoyt Wilhelm | | 536 | 529 | 7 |
| 1959-08-14 | @ NYA | 114 | W 11-6 | 52-61 | 6 | 38,624 | Tom Brewer | Whitey Ford | Frank Baumann | Ryne Duren | Mike Fornieles | 547 | 535 | 12 |
| 1959-08-15 | @ NYA | 115 | W 12-4 | 53-61 | 6 | 37,283 | Frank Sullivan | Eli Grba | Frank Sullivan | Eli Grba | Leo Kiely | 559 | 539 | 20 |
| 1959-08-16 | @ NYA | 116 | W 6-5 | 54-62 | 6 | 0 | Jerry Casale | Duke Maas | Ike Delock | Duke Maas | Leo Kiely | 565 | 544 | 21 |
| 1959-08-16 | @ NYA | 117 | L 2-4 | 54-62 | 6 | 46,717 | Bill Monbouquette | Ralph Terry | Ralph Terry | Bill Monbouquette | Bob Turley | 567 | 548 | 19 |
| 1959-08-18 | @ KC1 | 118 | W 5-4 | 55-62 | 6 | 11,240 | Tom Brewer | Johnny Kucks | Mike Fornieles | Ray Herbert | Leo Kiely | 572 | 552 | 20 |
| 1959-08-19 | @ KC1 | 119 | L 3-6 | 55-63 | 6 | 8,753 | Frank Sullivan | Bud Daley | Bud Daley | Frank Sullivan | | 575 | 558 | 17 |
| 1959-08-20 | @ KC1 | 120 | W 11-10 | 56-63 | 6 | 6,938 | Jerry Casale | John Tsitouris | Earl Wilson | Tom Sturdivant | Tom Brewer | 586 | 568 | 18 |
| 1959-08-21 | @ DET | 121 | L 0-2 | 56-64 | 6 | 16,781 | Bill Monbouquette | Paul Foytack | Paul Foytack | Bill Monbouquette | | 586 | 570 | 16 |
| 1959-08-22 | @ DET | 122 | W 7-1 | 57-64 | 6 | 8,632 | Frank Baumann | Don Mossi | Frank Baumann | Don Mossi | | 593 | 571 | 22 |
| 1959-08-23 | @ CLE | 123 | L 0-1 | 57-66 | 6 | 0 | Tom Brewer | Jim Perry | Jim Perry | Tom Brewer | | 593 | 572 | 21 |
| 1959-08-23 | @ CLE | 124 | L 2-6 | 57-66 | 6 | 26,208 | Al Schroll | Mike Garcia | Jack Harshman | Al Schroll | | 595 | 578 | 17 |
| 1959-08-25 | @ CHA | 125 | L 4-5 | 57-67 | 7 | 27,002 | Frank Sullivan | Dick Donovan | Turk Lown | Mike Fornieles | | 599 | 583 | 16 |
| 1959-08-26 | @ CHA | 126 | W 7-6 | 58-67 | 6 | 22,497 | Bill Monbouquette | Early Wynn | Bill Monbouquette | Early Wynn | Mike Fornieles | 606 | 589 | 17 |
| 1959-08-27 | @ CHA | 127 | L 1-5 | 58-68 | 7 | 11,703 | Frank Baumann | Barry Latman | Barry Latman | Frank Baumann | Gerry Staley | 607 | 594 | 13 |
| 1959-08-28 | vs BAL | 128 | W 6-4 | 59-68 | 6 | 18,071 | Tom Brewer | Hal Brown | Nelson Chittum | Billy Loes | | 613 | 598 | 15 |
| 1959-08-29 | vs BAL | 129 | W 4-1 | 60-68 | 6 | 10,114 | Jerry Casale | Milt Pappas | Jerry Casale | Milt Pappas | | 617 | 599 | 18 |
| 1959-08-30 | vs BAL | 130 | W 3-0 | 61-68 | 6 | 11,134 | Frank Sullivan | Hoyt Wilhelm | Frank Sullivan | Hoyt Wilhelm | | 620 | 599 | 21 |
| 1959-08-31 | vs WS1 | 131 | W 4-3 | 62-68 | 6 | 21,907 | Bill Monbouquette | Bill Fischer | Mike Fornieles | Chuck Stobbs | | 624 | 602 | 22 |
| 1959-09-01 | vs WS1 | 132 | L 4-7 | 62-69 | 6 | 6,317 | Earl Wilson | Camilo Pascual | Camilo Pascual | Earl Wilson | Tex Clevenger | 628 | 609 | 19 |
| 1959-09-02 | @ BAL | 133 | L 0-4 | 62-70 | 6 | 7,473 | Tom Brewer | Billy O'Dell | Billy O'Dell | Tom Brewer | | 628 | 613 | 15 |
| 1959-09-03 | @ BAL | 134 | L 4-5 | 62-71 | 6 | 8,754 | Frank Baumann | Hal Brown | Hal Brown | Frank Baumann | Billy Loes | 632 | 618 | 14 |
| 1959-09-04 | @ WS1 | 135 | L 3-4 | 62-72 | 6 | 4,960 | Frank Sullivan | Tex Clevenger | Tex Clevenger | Frank Sullivan | Dick Hyde | 635 | 622 | 13 |
| 1959-09-05 | @ WS1 | 136 | L 2-14 | 62-73 | 6 | 4,283 | Bill Monbouquette | Camilo Pascual | Camilo Pascual | Bill Monbouquette | | 637 | 636 | 1 |
| 1959-09-06 | @ WS1 | 137 | W 2-1 | 63-73 | 6 | 7,009 | Tom Brewer | Pedro Ramos | Tom Brewer | Pedro Ramos | | 639 | 637 | 2 |
| 1959-09-07 | vs NYA | 138 | W 12-4 | 64-73 | 6 | 19,995 | Jerry Casale | Duke Maas | Jerry Casale | Duke Maas | Mike Fornieles | 651 | 641 | 10 |
| 1959-09-09 | vs DET | 139 | L 1-3 | 64-74 | 6 | 13,406 | Frank Sullivan | Jim Bunning | Jim Bunning | Frank Sullivan | | 652 | 644 | 8 |
| 1959-09-10 | vs DET | 140 | W 7-3 | 65-74 | 6 | 3,294 | Bill Monbouquette | Frank Lary | Bill Monbouquette | Frank Lary | | 659 | 647 | 12 |
| 1959-09-11 | vs KC1 | 141 | L 6-8 | 65-75 | 6 | 10,409 | Tom Brewer | John Tsitouris | John Tsitouris | Tom Brewer | Al Grunwald | 665 | 655 | 10 |
| 1959-09-12 | vs KC1 | 142 | W 4-3 | 66-75 | 6 | 7,156 | Jerry Casale | Tom Sturdivant | Jerry Casale | Tom Sturdivant | | 669 | 658 | 11 |
| 1959-09-13 | vs CHA | 143 | L 1-3 | 66-76 | 6 | 26,720 | Frank Sullivan | Bob Shaw | Bob Shaw | Frank Sullivan | Turk Lown | 670 | 661 | 9 |
| 1959-09-14 | vs CHA | 144 | W 9-3 | 67-76 | 6 | 3,676 | Bill Monbouquette | Dick Donovan | Bill Monbouquette | Dick Donovan | | 679 | 664 | 15 |
| 1959-09-15 | vs CLE | 145 | W 1-0 | 68-76 | 6 | 8,456 | Tom Brewer | Mudcat Grant | Tom Brewer | Mudcat Grant | | 680 | 664 | 16 |
| 1959-09-16 | vs CLE | 146 | W 6-5 | 69-76 | 6 | 3,006 | Jerry Casale | Gary Bell | Nelson Chittum | Jim Perry | | 686 | 669 | 17 |
| 1959-09-18 | @ NYA | 147 | W 6-4 | 70-76 | 6 | 15,556 | Frank Baumann | Duke Maas | Frank Baumann | Duke Maas | Mike Fornieles | 692 | 673 | 19 |
| 1959-09-19 | @ NYA | 148 | L 1-3 | 70-77 | 6 | 24,830 | Bill Monbouquette | Whitey Ford | Whitey Ford | Bill Monbouquette | | 693 | 676 | 17 |
| 1959-09-20 | @ NYA | 149 | L 4-7 | 70-78 | 6 | 17,667 | Tom Brewer | Bob Turley | Duke Maas | Tom Brewer | Jim Coates | 697 | 683 | 14 |
| 1959-09-22 | vs BAL | 150 | W 4-3 | 71-78 | 6 | 9,344 | Frank Sullivan | Hoyt Wilhelm | Frank Sullivan | Hal Brown | Mike Fornieles | 701 | 686 | 15 |
| 1959-09-23 | vs BAL | 151 | W 4-0 | 72-78 | 6 | 2,199 | Jerry Casale | Jack Fisher | Jerry Casale | Jack Fisher | | 705 | 686 | 19 |
| 1959-09-25 | vs WS1 | 152 | W 10-4 | 73-78 | 5 | 9,089 | Earl Wilson | Tex Clevenger | Mike Fornieles | Dick Hyde | | 715 | 690 | 25 |
| 1959-09-26 | vs WS1 | 153 | W 5-4 | 74-78 | 5 | 5,428 | Bill Monbouquette | Camilo Pascual | Nelson Chittum | Bill Fischer | | 720 | 694 | 26 |
| 1959-09-27 | vs WS1 | 154 | W 6-2 | 74-78 | 5 | 9,110 | Jerry Casale | Jim Kaat | Jerry Casale | Jim Kaat | Frank Baumann | 726 | 696 | 30 |