| Rank | Student | Grade | School | Year | | ER | IP | Total |
| 1 | Kacey Marshall | Sr | New Franklin | 1989 | | 0 | 108 | 0.000 |
| 2 | Jill Wilcoxson | Sr | North Harrison | 1996 | | 1 | 121.2 | 0.058 |
| 3 | Lauren Delaney | So | Helias Catholic | 2003 | | 2 | 168 | 0.083 |
| 4 | Jacquelyn Bishop | Sr | Kirksville | 2009 | | 2 | 164.1 | 0.085 |
| 5 | Lauren Delaney | Sr | Helias Catholic | 2005 | | 2 | 160 | 0.088 |
| 6 | Lauren Delaney | Jr | Helias Catholic | 2004 | | 2 | 137 | 0.102 |
| 7 | Jen Bruck | Sr | Ft. Zumwalt West | 2003 | | 2 | 136 | 0.103 |
| 8 | Jennifer Kempf | Sr | Bishop LeBlond | 2004 | | 3 | 191.2 | 0.110 |
| 9 | Chelsea Fuemmeler | Jr | Salisbury | 2004 | | 3 | 190 | 0.111 |
| 10 | Mac Morgan | Jr | Sherwood | 2019 | | 3 | 175.1 | 0.120 |
| 11 | Kenya Fuemmeler | Sr | Salisbury | 2002 | | 3 | 171 | 0.123 |
| 12 | Maddy Colin | Jr | College Heights Christian | 2022 | | 21 | 141.1 | 1.040 |
| 13 | Maddy Colin | So | College Heights Christian | 2021 | | 20 | 131 | 1.069 |
| 14 | Anna Grace Christ | Sr | Rock Bridge | 2022 | | 17 | 109 | 1.092 |
| 15 | Taylor Brown | Jr | Washington | 2022 | | 20 | 125 | 1.120 |
| 16 | Zoe Martin | Sr | Sacred Heart | 2023 | | 49 | 121 | 2.835 |