Numerous Best Games this weekend (below), 5 Upsets, and 3 Best Upsets (which are marked with an asterisks).
| – | Team | Rank | VS | Rank | Opp Team | Details |
| 1 | North Carolina | #1 | 15 – 4 | #6 | Virginia | 04/18/2021 |
| 2 | Boston College | #2 | 18 – 12 | #5 | Notre Dame | 04/17/2021 |
| 3 | North Carolina | #1 | 20 – 8 | #6 | Virginia | 04/16/2021 |
| 4 | Northwestern | #4 | 19 – 10 | #21 | Michigan | 04/18/2021 |
| 5 | Florida | #8 | 22 – 9 | #24 | Vanderbilt | 04/18/2021 |
| 6 | Florida | #8 | 17 – 7 | #24 | Vanderbilt | 04/16/2021 |
| 7 | Johns Hopkins | #14 | 13 – 11 | #19 | Penn State | 04/18/2021 |
| 8* | Rutgers | #17 | 16 – 14 | #16 | Maryland | 04/18/2021 |
| 9 | Drexel | #9 | 15 – 11 | #25 | Hofstra | 04/18/2021 |
| 10 | Syracuse | #3 | 19 – 7 | #31 | Louisville | 04/18/2021 |
| 11 | Syracuse | #3 | 19 – 5 | #31 | Louisville | 04/16/2021 |
| 12* | Ohio State | #22 | 12 – 9 | #21 | Michigan | 04/16/2021 |
| 13 | Stanford | #10 | 22 – 21 | #36 | Arizona State | 04/16/2021 |
| 14 | James Madison | #26 | 14 – 12 | #28 | Towson | 04/18/2021 |
| 15 | Stanford | #10 | 16 – 15 | #45 | USC | 04/18/2021 |
| 16 | Duke | #7 | 13 – 7 | #53 | Virginia Tech | 04/17/2021 |
| 17 | Denver | #15 | 12 – 11 | #51 | Marquette | 04/18/2021 |
| 18 | Denver | #15 | 16 – 6 | #51 | Marquette | 04/16/2021 |
| 19 | Loyola | #13 | 20 – 3 | #55 | Bucknell | 04/16/2021 |
| 20* | Villanova | #44 | 13 – 12 | #35 | UConn | 04/18/2021 |
| 21 | UConn | #35 | 14 – 7 | #44 | Villanova | 04/16/2021 |
| 22 | UMass | #23 | 21 – 10 | #63 | Duquesne | 04/18/2021 |
| 23 | Davidson | #29 | 20 – 13 | #65 | George Washington | 04/16/2021 |
| 24 | UMass | #23 | 17 – 7 | #73 | La Salle | 04/16/2021 |
| 25 | UC Davis | #38 | 19 – 9 | #62 | Oregon | 04/17/2021 |
