| Rank | INT | Student | School | Opponent | Date | |
| 1 | 10 | | Montgomery County | Lutheran (St. Peters) | 10/25/2003 | |
| 2 | 7 | | Chillicothe | Tarkio | 10/23/1998 | |
| 2 | 7 | | South Callaway | Montgomery County | 10/20/2023 | |
| 4 | 6 | | Chillicothe | Milan | 10/3/1969 | |
| 4 | 6 | | Lexington | Marshall | 9/10/1970 | |
| 4 | 6 | | Chillicothe | Kirksville | 11/8/1979 | |
| 4 | 6 | | O'Hara | St. Pius X (Kansas City) | 11/12/1980 | |
| 4 | 6 | | Vianney | St. Mary's (St. Louis) | 10/15/1982 | |
| 4 | 6 | | O'Hara | Paseo Academy | 10/8/1988 | |
| 4 | 6 | | O'Hara | Lincoln | 10/2/1999 | |
| 4 | 6 | | St. Louis University | Vianney | 9/22/2000 | |
| 4 | 6 | | St. Vincent | East Buchanan | 11/27/2004 | at Dome |
| 4 | 6 | | St. Vincent | East Buchanan | 11/27/2004 | |
| 4 | 6 | | Mound City | Stewartsville | 11/13/2005 | 8-Man |
| 4 | 6 | | Parkway North | Parkway West | 11/1/2013 | |
| 4 | 6 | | Westran | Paris | 10/23/2020 | |
| 4 | 6 | | Drexel | St. Paul Lutheran (Concordia) | 10/22/2021 | |
| 18 | 5 | | Mound City | St. Joseph Christian | 11/26/2010 | |
| 18 | 5 | | Lamar | Trinity Catholic | 11/25/2016 | |
| 18 | 5 | | Hayti | Lincoln | 12/1/2018 | Class 1 |