Senior guard Andre Young led the Tigers past Virginia.
Clemson outscored Virginia 8-0 over a 5:31 stretch late in the second half to break open a tight game, and defeat the turnover-plagued Cavaliers 60-48.
After a driving layup by Jontel Evans cut the Tigers' lead to 44-41, Clemson got baskets from Tanner Smith and Devon Booker to expand their margin to seven.
With Virginia teetering on the edge of a knockout, the Cavaliers turned the ball over on three of their next four possessions.
Two more baskets by Rod Hall and Booker made the lead 52-41 with under three minutes left to play. Virginia would get no closer than eight points in the remainder of the game.
The win by Clemson was the sixth straight by the home team in this series, and avenged a 65-61 loss to the Cavaliers earlier this year in Charlottesville.
Tanner Smith and Andre Young led a balanced Tigers' scoring attack with 13 points each.
Virginia was led by Jontel Evans, who matched his career high with 17 points. Mike Scott chipped in with 13 points and eight rebounds.
Freshman Malcolm Brogdon, making his first career start in place of Joe Harris, added nine points.
Harris, UVA's second-leading scorer and rebounder, fractured his left, non-shooting hand against North Carolina on Saturday. With the hand wrapped in a protective padding, Harris came off of the bench to play 21 minutes. He proved ineffective, shooting 1-5 for two points—while committing three turnovers.
The first half was played in a six-point range, and was tied at the break 24-24.
The game remained tight throughout the first half of the second stanza.
The key play came on what appeared to be a missed call by the officials.
With Clemson leading 44-41, Brogdon stole the ball from Smith and threw it ahead to Evans, who missed the driving layup. Harris grabbed the rebound and went up for the put back, but appeared to be hacked across both arms by Milton Jennings.
Jennings grabbed the loose ball, and then he threw a court-length pass to Smith for an easy layup on the other end.
Instead of the lead being one, it was five—and the Cavs never recovered.
Virginia was again dismal from beyond the arc, making just 3-16 attempts.
The Tigers' defense forced 18-Virginia turnovers. Also, it made it difficult to get the ball to Scott in the low post. The result: Scott failed to get to the free-throw line for the second game in a row.
In fact, Virginia matched a 30-year-old team mark by shooting just one free throw in the game.
The Cavaliers have now lost consecutive games for the first time this year. They fall to 19-6 overall and 6-5 in the ACC.
Clemson climbed over the .500 mark to 13-12 overall and 5-6 in conference play.
Both teams return to action on Saturday. Virginia will entertain Maryland, while the Tigers go to Chapel Hill to play North Carolina.