| Rank | Student | School | Years | | SO | IP | Total |
| 1 | Bryce D Taylor | Northeast (Cairo) | 2017-2020 | | 229 | 102 | 15.716 |
| 2 | Jon Barratt | Hillcrest | 2001-2003 | | 328 | 171 | 13.427 |
| 3 | Sam LeCure | Helias Catholic | 1999-2002 | | 445 | 232 | 13.427 |
| 4 | Joe Kassanavoid | Lawson | 2005-2008 | | 345 | 183.1 | 13.173 |
| 5 | Cody Burkhardt | Hermitage | 2006-2009 | | 431 | 235.1 | 12.820 |
| 6 | Derrick Morris | Walnut Grove | 2005-2008 | | 391 | 217 | 12.613 |
| 7 | Jacob Turner | Westminster Christian Academy | 2006-2009 | | 305 | 171.1 | 12.461 |
| 8 | Matt Gilmer | Central (New Madrid County) | 1990-1993 | | 395 | 222 | 12.455 |
| 9 | Casen Grant Murphy | Central (Park Hills) | 2020-2023 | | 337 | 191.1 | 12.329 |
| 10 | Owen Reid | Moberly | 2002-2005 | | 255 | 149.2 | 11.927 |
| 11 | Matt Skyles | Mansfield | 1993-1996 | | 344 | 203.2 | 11.823 |
| 12 | Wyatt Baker Sparks | Aurora | 2014-2017 | | 385 | 228.1 | 11.803 |
| 13 | Logan Agan | Vienna | 2015-2018 | | 338 | 211 | 11.213 |
| 14 | Jacob Daniel Weirich | Jefferson City | 2014-2017 | | 277 | 207 | 9.367 |