| Career - Losses | |||
| Rk | Player Name | Totals | |
| 1 | Jamie Moyer | 97 | |
| 2 | Kevin Gausman | 85 | |
| 3 | Chris Sale | 84 | |
| 4 | David Cone | 73 | |
| 5 | Roy Halladay | 59 | |
| 6 | Andy Pettitte | 55 | |
| 7 | Kenley Jansen | 49 | |
| 8 | Julio Urias | 43 | |
| 9 | Jon Gray | 42 | |
| 10 | Jeff Fassero | 40 | |
| 11 | Gil Heredia | 36 | |
| 12 | Ian Kennedy | 35 | |
| 13 | Greg Swindell | 34 | |
| 14 | Ted Lilly | 34 | |
| 15 | C.C. Sabathia | 33 | |
| 16 | Jonathan Papelbon | 33 | |
| 17 | Mark Buehrle | 32 | |
| 18 | Pete Harnisch | 30 | |
| 19 | Derek Lowe | 29 | |
| 20 | Anibal Sanchez | 29 | |
| 21 | Robbie Ray | 29 | |
| 22 | Jose DeJesus | 28 | |
| 23 | Carlos Zambrano | 26 | |
| 24 | Jose Guzman | 25 | |
| 25 | Edwin Diaz | 22 | |
| Single Season - Losses | |||||
| Rk | Player Name | Totals | Year | ||
| 1 | Martin Perez | 20 | 2020 | ||
| 2 | Carlos Zambrano | 19 | 2006 | ||
| 3 | Daniel Norris | 19 | 2018 | ||
| 4 | Jamie Moyer | 18 | 1998 | ||
| 5 | Oil Can Boyd | 18 | 1991 | ||
| 6 | Jose DeJesus | 18 | 1991 | ||
| 7 | Jose Guzman | 17 | 1992 | ||
| 8 | Gil Heredia | 17 | 2000 | ||
| 9 | C.C. Sabathia | 17 | 2003 | ||
| 10 | David Cone | 16 | 1994 | ||
| 11 | Roy Halladay | 16 | 2011 | ||
| 12 | Robbie Ray | 16 | 2023 | ||
| 13 | Julio Urias | 16 | 2023 | ||
| 14 | Greg Maddux | 15 | 1990 | ||
| 15 | Bob Tewksbury | 15 | 1992 | ||
| 16 | John Tudor | 15 | 1991 | ||
| 17 | Pete Harnisch | 15 | 1999 | ||
| 18 | Reynaldo Lopez | 15 | 2018 | ||
| 19 | Kevin Gausman | 15 | 2019 | ||
| 20 | Jon Lester | 15 | 2020 | ||
| 21 | Bobby Miller | 15 | 2024 | ||
| 22 | Matt Clement | 14 | 2001 | ||
| 23 | Jamie Moyer | 14 | 2001 | ||
| 24 | Andy Pettitte | 14 | 1999 | ||
| 25 | C.C. Sabathia | 14 | 2002 | ||