| away Saturday, February 08 | Davidson | Davidson, N.C. | 5:00 PM | W, 14 - 6 | |
| away Wednesday, February 12 | Vanderbilt | Nashville, Tenn. | 3:00 PM | W, 20 - 12 | |
| home Sunday, February 16 | Stetson | Clemson, S.C. | Clemson Lacrosse Complex | 12:00 PM | W, 26 - 6 | |
| away Saturday, February 22 | No. 11/10 Notre Dame * | South Bend, Ind. | 8:00 PM | W, 12 - 11 | |
| away Saturday, March 01 | No. 6/5 Syracuse * | Syracuse, N.Y. | 12:00 PM | W, 9 - 8 | |
| home Tuesday, March 04 | Queens | Clemson, S.C. | Clemson Lacrosse Complex | 4:00 PM | W, 25 - 5 | |
| home Saturday, March 08 | No. 17/18 Duke * | Clemson, S.C. | Clemson Lacrosse Complex | 12:00 PM | L, 11 - 12 | |
| home Tuesday, March 11 | Mercer | Clemson, S.C. | Clemson Lacrosse Complex | 3:00 PM | L, 10 - 11 | |
| away Saturday, March 15 | No. 2/2 North Carolina * | Chapel Hill, N.C. | 12:00 PM | L, 5 - 18 | |
| home Thursday, March 20 | No. 9/8 Florida | Clemson, S.C. | Clemson Lacrosse Complex | 12:00 PM | L, 10 - 16 | |
| home Sunday, March 23 | Louisville * | Clemson, S.C. | Clemson Lacrosse Complex | 12:00 PM | W, 14 - 2 | |
| home Wednesday, March 26 | UAlbany | Clemson, S.C. | Clemson Lacrosse Complex | 6:00 PM | W, 21 - 8 | |
| home Saturday, March 29 | California * | Clemson, S.C. | Clemson Lacrosse Complex | 12:00 PM | W, 19 - 3 | |
| home Tuesday, April 01 | East Carolina | Clemson, S.C. | Clemson Lacrosse Complex | 5:00 PM | W, 15 - 4 | |
| away Saturday, April 05 | Virginia Tech * | Blacksburg, Va. | 12:00 PM | W, 18 - 6 | |
| away Thursday, April 10 | No. 10/9 Stanford * | Stanford, Calif. | 6:00 PM | L, 8 - 14 | |
| home Thursday, April 17 | Pittsburgh * | Clemson, S.C. | Clemson Lacrosse Complex | 5:00 PM | W, 14 - 6 | |
| neutral Wednesday, April 23 | No.10/9 [4] Duke | Charlotte, N.C. | American Legion Memorial Stadium | 2:00 PM | W, 15 - 7 | |
| neutral Friday, April 25 | No. 1/1 [1] North Carolina | Charlotte, N.C. | American Legion Memorial Stadium | 5:00 PM | L, 7 - 17 | |
| neutral Friday, May 09 | No. 16/15 Navy | Chapel Hill, N.C. | 5:00 PM | W, 11 - 8 | |
| away Sunday, May 11 | No. 1/1 [1] North Carolina | Chapel Hill, N.C. | 12:00 PM | L, 9 - 18 | |
No. 16/15 Navy ![No. 1/1 [1] North Carolina](https://clemsontigers.com/wp-content/uploads/2021/02/UNC-Logo_400x200.png){kind=logo}
No. 1/1 [1] North Carolina 
