Numerous Best Games this weekend (below), 0 Upsets, and 0 Best Upsets (which are marked with an asterisks).
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | Indiana Tech | #2 | 13 – 6 | #12 | Concordia (Mich.) | 04/17/2021 |
| 2 | Benedictine (Kan.) | #5 | 19 – 11 | #18 | Ottawa (Kan.) | 04/17/2021 |
| 3 | William Penn (Iowa) | #11 | 9 – 6 | #14 | Missouri Baptist | 04/17/2021 |
| 4 | Columbia (Mo.) | #3 | 19 – 2 | #23 | Saint Mary (Kan.) | 04/17/2021 |
| 5 | Lourdes (Ohio) | #8 | 19 – 10 | #20 | Taylor (Ind.) | 04/17/2021 |
| 6 | St. Ambrose (Iowa) | #4 | 21 – 9 | #24 | Missouri Valley | 04/17/2021 |
| 7 | Aquinas (Mich.) | #9 | 18 – 13 | #34 | Michigan-Dearborn | 04/17/2021 |
| 8 | Tennessee Wesleyan | #13 | 13 – 9 | #31 | Webber International (Fla.) | 04/16/2021 |
| 9 | St. Andrews (N.C.) | #16 | 9 – 8 | #30 | SCAD Savannah (Ga.) | 04/16/2021 |
