Numerous Best Games this weekend. No upsets.
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | Benedictine (Kan.) | #7 | 14 – 4 | #8 | Missouri Baptist | 04/10/2021 |
| 2 | Reinhardt (Ga.) | #1 | 20 – 5 | #16 | St. Andrews (N.C.) | 04/10/2021 |
| 3 | Indiana Tech | #2 | 11 – 9 | #21 | Cleary (Mich.) (Mich.) | 04/10/2021 |
| 4 | Missouri Baptist | #8 | 12 – 10 | #17 | Ottawa (Kan.) | 04/09/2021 |
| 5 | St. Ambrose (Iowa) | #4 | 17 – 8 | #23 | Saint Mary (Kan.) | 04/11/2021 |
| 6 | St. Ambrose (Iowa) | #4 | 12 – 3 | #25 | Missouri Valley | 04/10/2021 |
| 7 | Tennessee Wesleyan | #12 | 11 – 8 | #24 | SCAD Savannah (Ga.) | 04/11/2021 |
| 8 | Keiser (Fla.) | #5 | 26 – 6 | #31 | Webber International (Fla.) | 04/10/2021 |
| 9 | William Penn (Iowa) | #13 | 15 – 3 | #33 | Midland (Neb.) | 04/10/2021 |
| 10 | Mount Vernon Nazarene (Ohio) | #18 | 12 – 1 | #28 | Saint Xavier (Ill.) | 04/09/2021 |
| 11 | Saint Mary (Kan.) | #23 | 11 – 6 | #34 | Clarke (Iowa) | 04/10/2021 |
| 12 | Missouri Valley | #25 | 13 – 1 | #34 | Clarke (Iowa) | 04/09/2021 |
