| Player | Losses |
|---|---|
| Walter Johnson | 63 |
| Carl Mays | 61 |
| Juan Marichal | 55 |
| Pete Alexander | 55 |
| Mordecai Brown | 54 |
| Nolan Ryan | 53 |
| Joe McGinnity | 53 |
| Tom Seaver | 52 |
| Bob Gibson | 50 |
| Curt Schilling | 50 |
| Bert Blyleven | 49 |
| Steve Carlton | 49 |
| Rube Waddell | 49 |
| Vic Willis | 49 |
| Bob Feller | 49 |
| Cy Young | 47 |
| Lefty Grove | 46 |
| Jack Chesbro | 46 |
| Ed Walsh | 46 |
| Randy Johnson | 45 |
| Jim Palmer | 43 |
| Chief Bender | 41 |
| Ed Plank | 40 |
| Bob Lemon | 40 |
| Pedro Martinez | 39 |
| Christy Mathewson | 39 |
| Spud Chandler | 39 |
| Sandy Koufax | 38 |
| Warren Spahn | 38 |
| Johan Santana | 37 |