The comeback was the program's second-biggest in school history, second only to a 31-point comeback against Tulane in 1950.
In addition to showing off his Monstar strength, Williamson went off for a game-high 27 points to go along with 12 rebounds as the Blue Devils overcame a 59-36 deficit with under 10 minutes to play.
Louisville led 38-29 at halftime despite Williamson's 13 first-half points.
The Blue Devils caught fire late down the stretch as they outscored the Cardinals 35-10 to stun the KFC Yum!
Louisville (17-8, 8-4) would get one last shot to send things to overtime, but a Christen Cunningham jumper rimmed out just before the final buzzer.
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Apprentice next will play Tuesday, Feb. 19, at home in an Eastern Metro Athletic Conference tournament quarterfinal against an opponent to be announced.
At times, the game seemed like a contest between the two heavyweights as Winston seemed to answer every Happ hook shot with a floater or 3-pointer.
Clemson had the No. 1 team in the nation on the ropes in Littlejohn Coliseum, and Coach K was so angry he benched his entire starting lineup midway through the second half. Barrett leads the team now in terms of scoring, averaging 23.1 points per game along with 7.2 rebounds and 3.7 assists.
Duke made 13 shots from 3-point range Saturday night at Virginia but missed its first five long-range shots against Louisville. They also knocked down just 33.3 percent of their 3-point attempts.
Roach committed three turnovers in the first six minutes of the game, but he eventually made a star turn, scoring 14 points in the first half, primarily with hard drives to the basket that resulted in layups and free throws.
Cam Reddish converted on a pair of free throws with 14 seconds remaining to earn the Blue Devils their 10th ACC win and 22nd overall win. It's going to be a tall task for the home team to keep pace with Zion, Barrett, Reddish and the rest of the Blue Devils in this game. The Cardinals stretched the margin to 48-32 early in the second half as Williamson picked up his third foul. I mean, not just outplayed, they outcompeted us.
Williamson's rebound finished yet another impressive night for the freshman.