Numerous Best Games this weekend and 1 Best Upset (marked with an asterisks below).
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | Le Moyne | #1 | 6 – 4 | #23 | Pace | 04/10/2021 |
| 2 | Tampa | #8 | 7 – 6 | #16 | Lynn | 04/10/2021 |
| 3 | Limestone | #12 | 21 – 11 | #32 | Coker | 04/10/2021 |
| 4 | Mercyhurst | #7 | 19 – 7 | #38 | Walsh | 04/10/2021 |
| 5 | Belmont Abbey | #14 | 17 – 7 | #35 | North Greenville | 04/10/2021 |
| 6 | Chestnut Hill | #17 | 23 – 9 | #41 | Caldwell | 04/10/2021 |
| 7 | Mount Olive | #10 | 21 – 9 | #49 | Emmanuel (Ga.) | 04/10/2021 |
| 8 | Bentley | #21 | 15 – 6 | #42 | Saint Michael’s | 04/10/2021 |
| 9 | Queens | #20 | 20 – 11 | #44 | Anderson (SC) | 04/10/2021 |
| 10 | Newberry | #11 | 21 – 8 | #58 | Mars Hill | 04/10/2021 |
| 11 | Saint Anselm | #13 | 21 – 2 | #56 | Assumption | 04/10/2021 |
| 12 | Lenoir-Rhyne | #2 | 18 – 6 | #67 | Lincoln Memorial | 04/09/2021 |
| 13 | Colorado Mesa | #25 | 19 – 2 | #46 | CSU Pueblo | 04/11/2021 |
| 14 | Rollins | #24 | 13 – 12 | #48 | Florida Southern | 04/10/2021 |
| 15 | Westminster | #27 | 17 – 11 | #46 | CSU Pueblo | 04/09/2021 |
| 16 | Maryville | #15 | 15 – 6 | #62 | Quincy | 04/10/2021 |
| 17 | Rockhurst | #33 | 12 – 5 | #45 | Lewis | 04/10/2021 |
| 18 | Colorado Mesa | #25 | 12 – 6 | #54 | Adams State | 04/09/2021 |
| 19 | Westminster | #27 | 16 – 7 | #54 | Adams State | 04/11/2021 |
| 20 | Georgian Court | #22 | 15 – 5 | #68 | Felician | 04/10/2021 |
| 21 | Montevallo | #31 | 22 – 8 | #69 | Shorter | 04/10/2021 |
| 22 | Wilmington | #43 | 17 – 14 | #61 | Post | 04/10/2021 |
| 23* | Alabama Huntsville | #57 | 12 – 11 | #50 | Lander | 04/10/2021 |
| 24 | Lake Erie | #47 | 21 – 3 | #70 | Wheeling | 04/10/2021 |
| 25 | Molloy | #52 | 18 – 4 | #65 | St. Thomas Aquinas | 04/10/2021 |
