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 | Cumberlands (Ky.) | #1 | 16 – 9 | #4 | Life (Ga.) | 04/23/2021 |
| 2 | Keiser (Fla.) | #2 | 16 – 6 | #6 | Georgetown (Ky.) | 04/23/2021 |
| 3* | Lawrence Tech (Mich.) | #12 | 17 – 10 | #7 | Siena Heights (Mich.) | 04/24/2021 |
| 4 | Benedictine (Kan.) | #9 | 23 – 3 | #10 | Missouri Baptist | 04/24/2021 |
