Numerous Best Games this weekend (below), 6 Upsets, and 1 Best Upset (which is marked with an asterisks).
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | Salisbury | #1 | 14 – 13 | #20 | St. Mary’s (MD) | 04/17/2021 |
| 2 | William Smith | #11 | 12 – 8 | #14 | RIT | 04/17/2021 |
| 3 | William Smith | #11 | 16 – 11 | #14 | RIT | 04/16/2021 |
| 4 | FDU-Florham | #7 | 19 – 7 | #42 | Misericordia | 04/17/2021 |
| 5* | Widener | #61 | 8 – 7 | #13 | Stevenson | 04/17/2021 |
| 6 | Christopher Newport | #26 | 17 – 13 | #53 | Moravian | 04/17/2021 |
| 7 | Hamilton | #35 | 11 – 10 | #44 | Trinity | 04/17/2021 |
| 8 | Wesleyan (CT) | #37 | 16 – 15 | #44 | Trinity | 04/18/2021 |
| 9 | Lynchburg | #33 | 23 – 13 | #51 | Southern Virginia | 04/17/2021 |
| 10 | Messiah | #2 | 17 – 5 | #85 | Lebanon Valley | 04/17/2021 |
| 11 | Farmingdale State | #36 | 16 – 9 | #67 | Maritime College | 04/16/2021 |
| 12 | Franklin & Marshall | #79 | 15 – 6 | #29 | Washington College | 04/17/2021 |
| 13 | Montclair State | #5 | 14 – 13 | #107 | Stockton | 04/17/2021 |
| 14 | Brockport | #19 | 22 – 9 | #93 | Oswego | 04/17/2021 |
| 15 | Western Connecticut | #10 | 9 – 4 | #108 | Plymouth State | 04/17/2021 |
| 16 | Nazareth | #38 | 15 – 9 | #84 | Utica | 04/17/2021 |
| 17 | Roanoke | #15 | 20 – 8 | #116 | Randolph-Macon | 04/17/2021 |
| 18 | Clarkson | #68 | 18 – 10 | #71 | St. Lawrence | 04/17/2021 |
| 19 | Clarkson | #68 | 13 – 9 | #71 | St. Lawrence | 04/16/2021 |
| 20 | Ithaca | #24 | 21 – 13 | #117 | Rochester | 04/17/2021 |
| 21 | Ithaca | #24 | 13 – 5 | #117 | Rochester | 04/16/2021 |
| 22 | Westfield State | #6 | 17 – 9 | #137 | Bridgewater State | 04/17/2021 |
| 23 | Tufts | #3 | 20 – 3 | #141 | Connecticut College | 04/17/2021 |
| 24 | Johnson & Wales (Providence) | #52 | 12 – 11 | #97 | St. Joseph’s College | 04/17/2021 |
| 25 | Roger Williams | #58 | 21 – 7 | #102 | U. of New England | 04/17/2021 |
