Codi Miller-McIntyre added 12 points for the Demon Deacons (11-3, 1-0), who took control with a 15-2 run midway through the second half to build a double-digit lead.
The Tar Heels (10-4, 0-1) made a late push to cut the deficit to 64-61 with about 2 minutes left, but got no closer as the Demon Deacons held on for their third win against a ranked opponent under fourth-year coach Jeff Bzdelik.
The win also snapped a four-game losing streak in the long-running series, giving Wake Forest its first win against North Carolina since 2010.
James Michael McAdoo had 13 points and eight rebounds to lead the Tar Heels, while J.P. Tokoto and Brice Johnson both added 12 points and nine rebounds.
But UNC leading scorer Marcus Paige finished with just eight points on 3-for-12 shooting, marking the first time he has failed to score in double figures all season. He and Leslie McDonald, UNC's only other reliable outside shooter, combined to miss 13 of 15 shots from behind the arc.
This one ended up fitting in with the Tar Heels' wildly unpredictable ways this season. They have beaten highly ranked Michigan State, Kentucky and reigning national champion Louisville, but have also lost to Belmont, UAB and Texas. Now they have a fourth loss against an unranked opponent.
As for Wake Forest, it marked the second straight season Bzdelik's Demon Deacons have beaten a ranked league opponent at home. Last season, it was North Carolina State and eventual ACC champion Miami.
The Demon Deacons took control with a 15-2 run, getting baskets from six players - including two off backdoor cuts - to break a 38-all tie and take a 53-40 lead on Madison Jones' shot that bounced off the back of the rim and dropped through the net at the 10:08 mark.
While the Demon Deacons didn't keep the pedal to the floor to stay in control, the Tar Heels just weren't able to string together enough defensive stops or baskets to rally, either.
They got as close as three points and had a chance to get closer, but Tokoto missed a short shot after a backcourt steal that could have cut the deficit to one with about a minute left.
Jones grabbed the rebound and the Demon Deacons pushed it ahead to McKie, who hit a layup while drawing a foul for a three-point play that made it 67-61 with 1:03 left. UNC never got the margin back to a single-possession game again, shooting just 39 percent in a loss that had Wake Forest students and fans running to midcourt to celebrate at the horn.