Numerous Best Games this weekend (below), 4 Upsets, and 2 Best Upsets (which are marked with an asterisks).
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | West Chester | #2 | 12 – 10 | #13 | East Stroudsburg | 04/17/2021 |
| 2 | Seton Hill | #6 | 10 – 8 | #27 | Mercyhurst | 04/17/2021 |
| 3 | Grand Valley State | #11 | 18 – 6 | #28 | Northern Mich. | 04/18/2021 |
| 4 | Le Moyne | #1 | 8 – 7 | #38 | Adelphi | 04/17/2021 |
| 5 | Grand Valley State | #11 | 19 – 9 | #28 | Northern Mich. | 04/16/2021 |
| 6 | Mount Olive | #19 | 17 – 12 | #30 | Belmont Abbey | 04/17/2021 |
| 7 | Pace | #9 | 18 – 7 | #40 | New Haven | 04/17/2021 |
| 8* | Shippensburg | #26 | 12 – 11 | #25 | Bloomsburg | 04/17/2021 |
| 9 | Rollins | #5 | 14 – 8 | #51 | Palm Beach Atl. | 04/17/2021 |
| 10 | Mercy | #22 | 18 – 9 | #36 | Georgian Court | 04/16/2021 |
| 11 | Saint Leo | #14 | 23 – 14 | #54 | Lynn | 04/17/2021 |
| 12 | Roberts Wesleyan | #10 | 16 – 9 | #61 | Molloy | 04/17/2021 |
| 13 | Lindenwood | #7 | 18 – 9 | #76 | Rockhurst | 04/18/2021 |
| 14 | Jefferson | #15 | 21 – 0 | #74 | Caldwell | 04/17/2021 |
| 15 | Shepherd | #33 | 12 – 11 | #57 | Lock Haven | 04/16/2021 |
| 16 | Lindenwood | #7 | 19 – 13 | #84 | Missouri Western | 04/16/2021 |
| 17 | Franklin Pierce | #23 | 10 – 9 | #69 | Stonehill | 04/18/2021 |
| 18 | Assumption | #16 | 16 – 4 | #77 | Saint Michael’s | 04/17/2021 |
| 19 | Wingate | #20 | 23 – 7 | #86 | Tusculum | 04/17/2021 |
| 20 | Davenport | #12 | 16 – 7 | #96 | Concordia-St. Paul | 04/18/2021 |
| 21 | Davenport | #12 | 15 – 9 | #96 | Concordia-St. Paul | 04/16/2021 |
| 22 | Maryville | #91 | 0 – 27 | #17 | UIndy | 04/16/2021 |
| 23 | Wilmington | #47 | 21 – 1 | #68 | Nyack | 04/17/2021 |
| 24 | Millersville | #48 | 11 – 9 | #67 | Kutztown | 04/17/2021 |
| 25 | Colorado Mesa | #35 | 17 – 10 | #80 | Colorado St.-Pueblo | 04/16/2021 |
