Rashad McCants scored 25 points and Raymond Felton 22 for the Tar Heels (6-1, 0-1), who have lost five straight games in the series.
Roy Williams lost for the first time since leaving Kansas for North Carolina after last season.
After each team scored only two points in the second overtime, the offenses came back in the third extra session.
North Carolina took a 111-107 lead on a dunk from Jawad Williams. But Taron Downey answered with a three-pointer, and Kyle Visser put the Demon Deacons ahead by 112-111 with a tip-in with 2:20 left.
After a bucket by Williams gave Wake Forest a three-point lead, Melvin Scott drained a three-pointer from the top of the key to tie the game at 114-114 with 1:03 left.
That's when Williams put the Demon Deacons ahead to stay. After his inside bucket, Williams hit two free throws to seal the victory with 2.4 seconds left.
Connecticut 104, Iona 54 - Ben Gordon recorded his first triple-double with 17 points, 16 rebounds and 11 assists, the last two of which were career highs, to lead top-ranked Connecticut (8-1) past Iona (2-5) in Hartford, Conn.
The game also marked the return of Emeka Okafor, who has been bothered by chronic back pain. He had 24 points and 10 rebounds against the Gaels, who were held to 29 percent shooting.
By halftime, Gordon had turned in one of his best stretches of defense. He pulled down 11 boards, all defensive, and had three of his five steals.
Gordon finished with 15 defensive rebounds. His teammate Denham Brown matched a career high with 22 points, which included a personal best of six three-pointers.
Kentucky 80, Indiana 41 - Chuck Hayes scored 22 points and Erik Daniels 19 to lead second-ranked Kentucky (6-0) in the rout of Indiana (4-4) in Indianapolis.
The Wildcats won their 26th straight regular-season game with a suffocating defense that rarely allowed the Hoosiers an open shot.
