Numerous Best Games this weekend, 3 upsets, and 1 Best Upset (marked with an asterisks below).
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | Lynchburg | #3 | 20 – 10 | #13 | Roanoke | 04/10/2021 |
| 2 | Hampden-Sydney | #5 | 22 – 13 | #26 | Randolph-Macon | 04/10/2021 |
| 3 | Stevenson | #12 | 10 – 9 | #19 | Eastern | 04/10/2021 |
| 4 | Southern Virginia | #14 | 15 – 12 | #34 | Saint Mary’s (Md) | 04/10/2021 |
| 5 | York | #7 | 15 – 3 | #47 | Lebanon Valley | 04/10/2021 |
| 6 | Ithaca | #10 | 12 – 11 | #45 | Clarkson | 04/10/2021 |
| 7 | Illinois Wesleyan | #20 | 17 – 11 | #46 | Carthage | 04/10/2021 |
| 8 | Misericordia | #29 | 30 – 9 | #37 | Delaware Valley | 04/10/2021 |
| 9* | Union | #57 | 10 – 6 | #15 | St. Lawrence | 04/10/2021 |
| 10 | Catholic | #40 | 28 – 10 | #50 | Moravian | 04/10/2021 |
| 11 | Gettysburg | #24 | 10 – 9 | #70 | Ursinus | 04/10/2021 |
| 12 | Christopher Newport | #4 | 16 – 7 | #97 | Mary Washington | 04/10/2021 |
| 13 | Centre | #27 | 8 – 5 | #79 | Rhodes | 04/11/2021 |
| 14 | Massachusetts Maritime | #53 | 18 – 5 | #64 | Bridgewater | 04/09/2021 |
| 15 | Endicott | #25 | 9 – 8 | #93 | Western New England | 04/10/2021 |
| 16 | Alfred | #42 | 12 – 8 | #81 | Utica | 04/10/2021 |
| 17 | Lasell | #51 | 12 – 11 | #72 | Norwich | 04/10/2021 |
| 18 | Otterbein | #41 | 13 – 3 | #86 | Capital | 04/10/2021 |
| 19 | Scranton | #23 | 10 – 9 | #107 | Elizabethtown | 04/10/2021 |
| 20 | Saint Mary’s (Md) | #34 | 13 – 12 | #97 | Mary Washington | 04/11/2021 |
| 21 | Geneseo | #39 | 16 – 7 | #102 | Brockport | 04/09/2021 |
| 22 | Keene State | #65 | 19 – 6 | #77 | Eastern Connecticut | 04/10/2021 |
| 23 | Salve Regina | #55 | 19 – 17 | #88 | Roger Williams | 04/10/2021 |
| 24 | Williams | #69 | 14 – 9 | #76 | Connecticut College | 04/10/2021 |
| 25 | Ohio Wesleyan | #18 | 10 – 4 | #128 | Wittenberg | 04/10/2021 |
