| Rank | Student | School | Years | | ER | IP | ERA |
| 1 | Lauren Delaney | Helias Catholic | 2002-2005 | | 9 | 596 | 0.106 |
| 2 | Taylor Baxter | Palmyra | 2006-2009 | | 20 | 639.1 | 0.219 |
| 3 | Jill Wilcoxson | North Harrison | 1994-1997 | | 12 | 320.2 | 0.262 |
| 4 | Deanna McQueen | Jefferson (Conception) | 1999-2002 | | 18 | 438 | 0.288 |
| 5 | Nicole Hudson | Webb City | 2005-2008 | | 26 | 502.2 | 0.362 |
| 6 | Katelyn Tolle | Bevier | 2006-2009 | | 19 | 365.2 | 0.364 |
| 7 | Kenya Fuemmeler | Salisbury | 1999-2002 | | 31 | 567 | 0.383 |
| 8 | Lory Mothersbaugh | Putnam County | 1994-1997 | | 28 | 505.1 | 0.388 |
| 9 | Katie L Shockley | Crocker | 2007-2010 | | 24 | 390.2 | 0.430 |
| 10 | Valerie Teter | Bevier | 2003-2006 | | 37 | 580.1 | 0.446 |
| 11 | Maddy Colin | College Heights Christian | 2020-2023 | | 116 | 481 | 1.688 |