Kerwin Walton had a career-high 19 points on 7-of-10 shooting, Armando Bacot scored 14, Garrison Brooks 12 and Walker Kessler added 10 for UNC (14-7, 8-5 ACC).
Louisville (11-5, 6-4) played for the first time in 19 days due to issues related to the coronavirus pandemic.
And it looked like it.
Carlik Jones hit a jumper to give the Cardinals a 2-0 lead but Walton answered with a 3-pointer 59 seconds into the game and UNC never again trailed.
Louisville shot just 33% from the field and made just 1 of 16 from 3-point range.
North Carolina outrebounded the Cardinals 45-34, blocked eight shots and outscored Louisville 58-32 in the paint.
Sharpe stole a pass from Charles Mineland, passed to RJ Davis and filled the right side of the lane for an alley-oop layup to make it 91-50 with 3:31 to play. Creighton Lebo's layup two minutes later capped a 22-0 run and gave UNC a 49-point lead.
Jones, the lone Louisville player to score in double figures, finished with 13 points.
The Tar Heels set season highs for points and field-goal percentage (60.9).
For more AP college basketball coverage: https://apnews.com/Collegebasketball and https://twitter.com/AP--Top25
Sharpe caps off UNC's win with big jam on a Louisville defender
R.J. Davis lobs up an alley-oop to Day'Ron Sharpe, who stuffs it down over a Louisville defender.