Virginia (29-2) led for 34 minutes and put five players in double figures while shooting 52.5 percent for the game. Guy's 19 points came on the heels of him spraining his MCL and being held scoreless in the Cavaliers' regular season finale last Saturday.
Devon Hall added 14 points for Virginia while freshman De'Andre Hunter chipped in with 12.
Virginia advances to the semifinals on Friday night, where it will meet No. 19 Clemson, a 90-82 winner over Boston College.
Louisville (20-13) cut Virginia's lead to four midway through the second half but got no closer than that as the Cavaliers padded their lead to coast to the 17-point win.
The Cardinals are now 1-8 against Virginia since joining the ACC and were held to 36.7 percent shooting. Junior Ray Spalding led the Cardinals with 16 points while Deng Adel added 13.
Virginia outrebounded Louisville 34-25 and had six players with at least three rebounds, including Guy, who led the Cavaliers with seven.
After taking a four-point lead two minutes into the game, Louisville was hit with a 20-5 Virginia run that put the Cavaliers in front by as many as 17 points during the first 20 minutes.
Louisville cut the Virginia lead to 38-27 at halftime after the Cardinals closed the half on a 6-0 run.
Virginia shot 48 percent in the half while Louisville was held to 36 percent but did make six of its 12 shots from beyond the arc.
--Field Level Media
Louisville | Virginia | |
Ray Spalding 16 | Scoring | Kyle Guy 19 |
Quentin Snider 3 | Assists | Devon Hall 5 |
Ray Spalding 6 | Rebounds | Kyle Guy 7 |
Ray Spalding 6 | Free Throws Made | De'Andre Hunter 3 |
Jordan Nwora 2 | Steals | Ty Jerome 2 |
Anas Mahmoud 2 | Blocks | Isaiah Wilkins 2 |
Team | Points | FG% | 3PM-3PA | FTM-FTA | Assists | Rebounds | Blocks | Steals | Turnovers |
Louisville | 58 | 36.7 | 9-21 | 13-14 | 11 | 22 | 2 | 5 | 8 |
Virginia | 75 | 52.5 | 7-18 | 6-7 | 13 | 29 | 2 | 5 | 7 |