Andre Young, Devin Booker and Demontez Stitt each scored 11 points during the loss, which put an end to this season's eight-game winning streak.
Bryan Narcisse provided a spark off the bench when Tanner Smith went down with a sprained knee at the end of the first half.
On a 4-of-6 shooting effort, Narcisse scored 10 and had a pair of steals.
Coming off an 85 percent second half shooting performance against Georgia Tech, Clemson struggled to make shots.
Jerai Grant, who entered the night as the school's all-time leader in field goal percentage, hit 1-of-12 from the field. Young and Stitt combined for a 4-of-17 performance behind the 3-point line.
As a team, Clemson shot 35 percent (25-of-71) from the field and from long range (10-of-29).
John Henson and Tyler Zeller patrolled the lane, combining for eight blocked shots.
North Carolina's spark off the bench came from Reggie Bullock, who scored 18.
Henson, Zeller and Harrison Barnes all scored in double-digits for the Tar Heels.
North Carolina also won the battle on the boards, 39-37.
Each team committed 14 turnovers.
The Tar Heels made more foul shots (17) than Clemson attempted (10).