Best Upsets are marked with an asterisks*. Some teams are under-rated due to having limited quality wins.
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | Columbia (Mo.) | #2 | 16 – 6 | #4 | St. Ambrose (Iowa) | 04/24/2021 |
| 2 | Indiana Tech | #3 | 17 – 10 | #8 | Lourdes (Ohio) | 04/23/2021 |
| 3 | Indiana Tech | #3 | 13 – 4 | #12 | Concordia (Mich.) | 04/24/2021 |
| 4 | Cumberlands (Ky.) | #6 | 14 – 5 | #11 | Tennessee Wesleyan | 04/23/2021 |
| 5 | Reinhardt (Ga.) | #1 | 26 – 4 | #16 | St. Andrews (N.C.) | 04/23/2021 |
| 6* | Concordia (Mich.) | #12 | 17 – 13 | #9 | Aquinas (Mich.) | 04/23/2021 |
