Numerous Best Games this weekend, 9 Upsets, and 3 Best Upsets (marked with an asterisks below).
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | St. Mary’s (MD) | #11 | 15 – 6 | #23 | Meredith | 04/11/2021 |
| 2 | Christopher Newport | #18 | 12 – 8 | #21 | Mary Washington | 04/10/2021 |
| 3 | St. Mary’s (MD) | #11 | 19 – 7 | #41 | Southern Virginia | 04/09/2021 |
| 4 | York | #13 | 17 – 7 | #56 | Lebanon Valley | 04/10/2021 |
| 5 | Messiah | #4 | 19 – 7 | #67 | Widener | 04/10/2021 |
| 6 | Roanoke | #9 | 17 – 14 | #65 | Shenandoah | 04/10/2021 |
| 7 | Misericordia | #24 | 17 – 14 | #51 | Stevens | 04/11/2021 |
| 8 | Carroll (WI) | #22 | 21 – 9 | #59 | UW-River Falls | 04/10/2021 |
| 9 | Marymount | #19 | 21 – 4 | #71 | Neumann | 04/10/2021 |
| 10* | Geneseo | #61 | 10 – 9 | #36 | St. John Fisher | 04/10/2021 |
| 11 | RIT | #6 | 13 – 12 | #106 | Rochester | 04/09/2021 |
| 12 | Western New England | #45 | 23 – 7 | #73 | Gordon | 04/10/2021 |
| 13 | TCNJ | #16 | 22 – 11 | #105 | Kean | 04/10/2021 |
| 14 | Hamilton | #62 | 17 – 9 | #72 | Wesleyan (CT) | 04/11/2021 |
| 15* | Wesleyan (CT) | #72 | 13 – 12 | #62 | Hamilton | 04/10/2021 |
| 16 | Tufts | #27 | 18 – 12 | #129 | Colby | 04/10/2021 |
| 17* | Transylvania | #117 | 18 – 15 | #40 | DePauw | 04/09/2021 |
| 18 | Rhodes | #37 | 24 – 3 | #123 | Berry | 04/11/2021 |
| 19 | Rhodes | #37 | 29 – 2 | #123 | Berry | 04/10/2021 |
| 20 | Nazareth | #39 | 23 – 3 | #124 | Sage | 04/10/2021 |
| 21 | Skidmore | #48 | 24 – 22 | #115 | Union | 04/09/2021 |
| 22 | Meredith | #23 | 20 – 5 | #143 | Averett | 04/10/2021 |
| 23 | Farmingdale State | #49 | 19 – 3 | #125 | Mount St. Mary | 04/09/2021 |
| 24 | FDU-Florham | #8 | 23 – 4 | #168 | Wilkes | 04/10/2021 |
| 25 | Hope | #34 | 16 – 11 | #146 | Trine | 04/10/2021 |
