After scoring just six points in Saturday's loss to then-No. 11 Virginia, Lee lifted the Cardinals to a hard-fought victory over the first-place Tar Heels by making 8 of 12 shots, including consecutive 3-pointers that helped provide a 55-50 lead with 9:35 remaining.
Chinanu Onuaku added a three-point play, Ray Spalding scored and Trey Lewis followed with a big layup and then two free throws with 26 seconds left for a four-point lead.
Lee sealed the win by making two more at the free throw line as Louisville (18-4, 7-2 Atlantic Coast Conference) handed the Tar Heels (19-3, 8-1) their first conference loss.
Onuaku had 12 points and 10 rebounds and Donovan Mitchell added 10 points for the Cardinals.
Justin Jackson's 16 points led North Carolina.