Best Upsets are marked with an asterisks*. Some teams are under-rated due to having limited quality wins.
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | Seton Hill | #2 | 12 – 5 | #5 | Mercy | 04/24/2021 |
| 2 | Lenoir-Rhyne | #3 | 19 – 14 | #6 | Wingate | 04/25/2021 |
| 3 | UIndy | #7 | 11 – 9 | #10 | Lindenwood | 04/24/2021 |
| 4 | Wingate | #6 | 14 – 10 | #14 | Limestone | 04/23/2021 |
| 5 | Rockhurst | #16 | 14 – 12 | #19 | Maryville | 04/24/2021 |
| 6* | Belmont Abbey | #23 | 12 – 7 | #12 | Mount Olive | 04/24/2021 |
| 7 | Lenoir-Rhyne | #3 | 20 – 8 | #34 | Tusculum | 04/23/2021 |
| 8 | Frostburg | #17 | 11 – 10 | #28 | Roberts Wesleyan | 04/24/2021 |
| 9 | Chestnut Hill | #13 | 22 – 11 | #41 | Dominican (NY) | 04/24/2021 |
| 10 | Adelphi | #4 | 15 – 6 | #51 | Assumption | 04/24/2021 |
| 11 | Bentley | #18 | 18 – 3 | #50 | Saint Rose | 04/24/2021 |
| 12 | Rollins | #21 | 17 – 14 | #53 | Florida Southern | 04/24/2021 |
| 13 | Pace | #20 | 20 – 1 | #61 | AIC | 04/24/2021 |
| 14 | Georgian Court | #25 | 15 – 9 | #57 | Caldwell | 04/24/2021 |
| 15 | Franklin Pierce | #36 | 9 – 5 | #47 | Saint Michael’s | 04/24/2021 |
| 16* | Saint Michael’s | #47 | 15 – 3 | #37 | Southern New Hampshire | 04/24/2021 |
| 17 | Colorado Mesa | #27 | 23 – 3 | #58 | Adams State | 04/25/2021 |
| 18 | Westminster | #29 | 21 – 2 | #58 | Adams State | 04/23/2021 |
| 19 | Walsh | #31 | 21 – 4 | #69 | Wheeling | 04/24/2021 |
| 20 | Wilmington | #49 | 15 – 1 | #68 | Felician | 04/24/2021 |
| 21 | Davis & Elkins | #54 | 18 – 15 | #66 | Alderson-Broaddus | 04/23/2021 |
| 22 | Alabama Huntsville | #59 | 19 – 2 | #65 | Shorter | 04/23/2021 |
