Numerous Best Games this weekend (below) and 2 Best Upsets (which are marked with an asterisks below).
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | Le Moyne | #1 | 11 – 10 | #16 | Bentley | 04/17/2021 |
| 2 | Adelphi | #4 | 14 – 9 | #17 | Pace | 04/17/2021 |
| 3* | Rockhurst | #21 | 9 – 5 | #11 | UIndy | 04/17/2021 |
| 4 | Limestone | #13 | 13 – 7 | #23 | Belmont Abbey | 04/17/2021 |
| 5 | Lynn | #14 | 11 – 10 | #33 | Saint Leo | 04/17/2021 |
| 6 | Lindenwood | #5 | 11 – 8 | #47 | Lewis | 04/17/2021 |
| 7 | Seton Hill | #10 | 17 – 7 | #44 | Lake Erie | 04/17/2021 |
| 8 | Saint Anselm | #12 | 15 – 6 | #42 | Franklin Pierce | 04/17/2021 |
| 9 | Lenoir-Rhyne | #3 | 27 – 8 | #59 | Mars Hill | 04/17/2021 |
| 10 | Mercyhurst | #8 | 25 – 5 | #60 | Alderson-Broaddus | 04/17/2021 |
| 11 | Maryville | #15 | 11 – 4 | #55 | Davenport | 04/17/2021 |
| 12 | Mount Olive | #9 | 17 – 7 | #64 | Lees-McRae | 04/17/2021 |
| 13 | Rollins | #25 | 10 – 5 | #54 | Palm Beach Atlantic | 04/17/2021 |
| 14 | Coker | #34 | 18 – 15 | #46 | Anderson (SC) | 04/17/2021 |
| 15 | Walsh | #31 | 12 – 9 | #52 | Molloy | 04/17/2021 |
| 16 | Montevallo | #27 | 13 – 11 | #58 | Alabama Huntsville | 04/17/2021 |
| 17 | Newberry | #19 | 21 – 3 | #68 | Lincoln Memorial | 04/17/2021 |
| 18 | Roberts Wesleyan | #26 | 26 – 4 | #61 | St. Thomas Aquinas | 04/17/2021 |
| 19 | Georgian Court | #22 | 17 – 8 | #70 | Post | 04/17/2021 |
| 20* | Assumption | #51 | 16 – 13 | #49 | Saint Michael’s | 04/17/2021 |
| 21 | Southern New Hampshire | #38 | 15 – 5 | #62 | AIC | 04/17/2021 |
| 22 | Emmanuel (Ga.) | #50 | 19 – 13 | #66 | Chowan | 04/17/2021 |
| 23 | Davis & Elkins | #56 | 19 – 11 | #69 | Wheeling | 04/17/2021 |
