The Tigers (18-4, 7-3) were up 44-28 at the half and looked like they would cruise to their first win over the Tar Heels (16-7, 5-5) since January 2010. Instead, Cameron Johnson and Joel Berry II rallied UNC back, with Berry's jumper tying it at 74 with 2:03 to play.
That's when Reed struck with his 3 from the left side to put Clemson ahead for good. Reed rebounded Johnson's miss moments later, and Elijah Thomas made an inside shot to go up 79-74.
North Carolina has its first three-game losing streak since the 2013-14 season.
On three point defense Roy says he has no answers and has never seen something like this in his whole life— Mark Armstrong (@ArmstrongABC11) January 31, 2018
Clemson fans rushed the court after the school's second win over North Carolina since March 2004.
Gabe DeVoe had 17 points, including five of Clemson's season-high 15 3-pointers.
Johnson had a career-high 32 points while Berry had 27, 19 of those coming in the second half.
The Tar Heels played almost all of the game without starting forward Theo Pinson, who strained his left shoulder when he crashed hard to the court going for a rebound.
North Carolina: The Tar Heels have a serious problem at the point brewing if Pinson needs time to recover from a left shoulder strain. North Carolina is already without an injured Seventh Woods and suspended Jalek Felton. Pinson was the lone experienced, reliable option to run things when Berry needs a breather.
Woods has been sidelined since December with a foot injury. Pinson hurt himself early against Clemson when he took a hard foul trying to get a rebound. Andrew Platek, a freshman who's averaged eight minutes a game this season, played 11 minutes in the first half.
READ MORE: UNC suspends freshman guard Jalek Felton
Clemson: The Tigers also needs ways to overcome their sudden lack of depth at forward. Starter Donte Grantham was lost for the season with a torn ACL against Notre Dame on Jan. 20. This past Sunday, Mark Donnal suffered a concussion and missed the contest with North Carolina. If Donnal's symptoms continue, Clemson must get production from freshmen Amir Simms and Malik William.
North Carolina returns home to play Pitt on Saturday night.
Clemson travels to Wake Forest on Saturday.