| Career - Losses | |||
| Rk | Player Name | Totals | |
| 1 | James Paxton | 71 | |
| 2 | Masahiro Tanaka | 59 | |
| 3 | R.A. Dickey | 48 | |
| 4 | John Means | 42 | |
| 5 | CC Sabathia | 38 | |
| 6 | Tyler Anderson | 33 | |
| 7 | Jeremy Hellickson | 32 | |
| 8 | Felix Hernandez | 26 | |
| 9 | Hyun-Jin Ryu | 25 | |
| 10 | Alex Cobb | 21 | |
| 11 | Hector Santiago | 19 | |
| 12 | Reynaldo Lopez | 19 | |
| 13 | Hyun Jin Ryu | 18 | |
| 14 | Ricky Nolasco | 17 | |
| 15 | Vincent Velasquez | 17 | |
| 16 | John Danks | 16 | |
| 17 | C.C. Sabathia | 16 | |
| 18 | Nathan Karns | 16 | |
| 19 | Luis Cessa | 16 | |
| 20 | Chris Stratton | 15 | |
| 21 | Liam Hendriks | 15 | |
| 22 | Daniel Hudson | 15 | |
| 23 | Erick Fedde | 15 | |
| 24 | Wily Peralta | 15 | |
| 25 | Wade Miley | 14 | |
| Single Season - Losses | |||||
| Rk | Player Name | Totals | Year | ||
| 1 | Hector Santiago | 19 | 2014 | ||
| 2 | Reynaldo Lopez | 19 | 2019 | ||
| 3 | R.A. Dickey | 18 | 2014 | ||
| 4 | John Means | 18 | 2021 | ||
| 5 | R.A. Dickey | 17 | 2016 | ||
| 6 | Ricky Nolasco | 17 | 2017 | ||
| 7 | John Danks | 16 | 2014 | ||
| 8 | Jeremy Hellickson | 16 | 2014 | ||
| 9 | Jeremy Hellickson | 16 | 2015 | ||
| 10 | C.C. Sabathia | 16 | 2015 | ||
| 11 | Nathan Karns | 16 | 2016 | ||
| 12 | Masahiro Tanaka | 16 | 2017 | ||
| 13 | James Paxton | 15 | 2015 | ||
| 14 | CC Sabathia | 15 | 2017 | ||
| 15 | Chris Stratton | 15 | 2018 | ||
| 16 | Erick Fedde | 15 | 2021 | ||
| 17 | Wily Peralta | 15 | 2022 | ||
| 18 | Wade Miley | 14 | 2016 | ||
| 19 | CC Sabathia | 14 | 2018 | ||
| 20 | Andrew Cashner | 14 | 2020 | ||
| 21 | R.A. Dickey | 13 | 2015 | ||
| 22 | Masahiro Tanaka | 13 | 2015 | ||
| 23 | Felix Hernandez | 13 | 2017 | ||
| 24 | Masahiro Tanaka | 13 | 2018 | ||
| 25 | John Means | 13 | 2020 | ||