| Rank | HR | Student | School | Opponent | Date | |
| 1 | 4 | Laura Marie Ashlock | Oak Park | Park Hill | 9/19/2009 | |
| 1 | 4 | Eileen Bridget Mcginnis | Marquette | Fox | 8/28/2017 | |
| 1 | 4 | Jaden LaBarge | Kickapoo | Rolla | 9/22/2020 | |
| 1 | 4 | Amelia Safiya Raziq | Francis Howell Central | Holt | 9/9/2024 | |
| 5 | 3 | Carolyn Adams | Osage | Versailles | 9/5/1996 | |
| 5 | 3 | Autumn Walker | Central (New Madrid County) | Blytheville (Ark.) | 4/2/2003 | |
| 5 | 3 | Kelsey Schulte | Eugene | Tuscumbia | 9/8/2006 | |
| 5 | 3 | Kirstain Burger | Notre Dame (Cape Girardeau) | Goreville (Ill.) | 9/17/2006 | |
| 5 | 3 | Hannah Hummel | Festus | Fox | 9/27/2008 | |
| 5 | 3 | Casey Kern | Kelly | Hillsboro | 9/27/2008 | |
| 5 | 3 | Carlie Anne Rose | Nixa | Neosho | 9/8/2009 | |
| 5 | 3 | Kelsey M Harrington | Rock Bridge | Lebanon | 9/27/2011 | |
| 5 | 3 | Jordan Shewmaker | Buffalo | Marshfield | 9/17/2013 | |
| 5 | 3 | Molly Carter | Hickman | Jefferson City | 10/10/2013 | |
| 5 | 3 | Maci Marshall | Dixon | Camdenton | 10/4/2014 | |
| 5 | 3 | Nicole Duncan | Centralia | Boonville | 10/5/2015 | |
| 5 | 3 | Kelsey Claire Lenox | Marquette | Webster Groves | 9/7/2016 | |
| 5 | 3 | Haylie Marie Mathes | Seckman | | 9/24/2016 | vs. Festus |
| 5 | 3 | Kaileigh Marie Dirden | Scott City | Advance | 3/29/2016 | |
| 5 | 3 | Carlie Sanders | Hillsboro | Fort Zumwalt North | 8/18/2017 | |
| 5 | 3 | Carlie Sanders | Hillsboro | Jefferson (Festus) | 9/18/2017 | |
| 5 | 3 | Abigail King | Christian | Trinity Catholic | 9/18/2017 | |
| 5 | 3 | Shelby Ann-Renee Webster | Camdenton | | 10/5/2018 | Vs Dixon |
| 5 | 3 | Alyson Marcum | Bernie | | 4/24/2018 | |
| 5 | 3 | Lanae Flowers | Van Buren | | 8/30/2018 | |
| 5 | 3 | Lea Moose | West Platte | | 9/4/2018 | |
| 5 | 3 | Maren Jones | Rock Bridge | Francis Howell Central | 10/28/2019 | |
| 5 | 3 | Catryn Nicole Cattoor | Jefferson (Festus) | | 10/8/2019 | |
| 5 | 3 | Brooklynn Fischer | Montgomery County | New Haven | 10/8/2020 | |
| 5 | 3 | Katerina L Wilds | Lee's Summit West | Parkway South | 10/29/2021 | |
| 5 | 3 | Kinzey Lea Woody | Fatima | Tuscumbia | 9/14/2021 | |
| 5 | 3 | Olyvia Lee Williams | Buffalo | Seymour | 4/18/2022 | |
| 5 | 3 | Kameryn Renee Tucker | Jackson | Marquette | 9/15/2022 | |
| 5 | 3 | Reese Van Pelt | Chaffee | Neelyville | 9/26/2022 | |
| 5 | 3 | Hailey Presley | Marion C. Early | Halfway | 9/10/2022 | |
| 5 | 3 | Grazia Marie Mazzola | Eureka | Eureka | 9/28/2023 | |
| 5 | 3 | Kylie Walker | Senath-Hornersville | Doniphan | 4/11/2023 | |
| 38 | 2 | Bailey Baird | Lee's Summit | | 1/1/2013 | Class 4 |
| 38 | 2 | Megan Ann Green | Jefferson City | | 9/4/2018 | 2 3run HRs |
| 38 | 2 | Kara Kaye Daly | Jefferson City | | 10/3/2018 | |
| 38 | 2 | Ashton Elizabeth Willis | Maysville | Gallatin | 10/19/2019 | |
| 38 | 2 | Ashley Lynn Brown | Maysville | South Harrison | 9/8/2020 | |
| 38 | 2 | Laney Halley | Iberia | Tuscumbia | 10/4/2021 | |
| 38 | 2 | Ireland Bloss | Marceline | Sherwood | 10/30/2021 | |
| 38 | 2 | Kinzey Lea Woody | Fatima | Fatima | 10/29/2022 | |
| 38 | 2 | Kinzey Lea Woody | Fatima | Chillicothe | 10/29/2022 | |
| 38 | 2 | Elysia Hand | Kearney | Helias Catholic | 10/28/2022 | |
| 38 | 2 | Elysia Hand | Kearney | Helias Catholic | 10/28/2022 | |
| 38 | 2 | Maleigh Lemings | Holcomb | Kennett | 5/3/2023 | |
| 38 | 2 | Kinlee Cochran | Iberia | Vienna | 10/5/2023 | |
| 38 | 2 | Kinlee Cochran | Iberia | Tuscumbia | 9/28/2023 | |
| 38 | 2 | Kya Yoakum | Iberia | Rolla | 10/9/2023 | |
| 38 | 2 | Kinlee Cochran | Iberia | Dixon | 9/26/2024 | |
| 38 | 2 | Kya Yoakum | Iberia | Capital City | 10/8/2024 | |
| 55 | 1 | Tracy Shad | Wheaton | | 1/1/1996 | Class 1 |
| 55 | 1 | Lily Dohogne | Notre Dame (Cape Girardeau) | | 1/1/2001 | Class 3 |
| 55 | 1 | Lindsey Barnhart | Silex | | 1/1/2012 | Class 1 |
| 55 | 1 | Madison Preston | Centralia | | 1/1/2016 | Class 2 |
| 55 | 1 | Ashton Elizabeth Willis | Maysville | Salisbury | 10/27/2018 | |
| 55 | 1 | Kimberly Anne Seabaugh | Kelly | DeSoto | 9/4/2020 | |
| 55 | 1 | Alaney Moore | Kelly | Chaffee | 10/5/2020 | |
| 55 | 1 | Alaney Moore | Kelly | Iberia | 10/22/2020 | |
| 55 | 1 | Kendyl Stuckey | Kelly | Iberia | 10/22/2020 | |