Jaron Blossomgame had a double-double of 14 points and 14 rebounds for the Tigers (11-4, 2-1 ACC) , who bested Duke for the first time since 2009.
Rod Hall (11 points) and Landry Nnoko (10, 13 rebounds) also played big roles for Clemson, which took a third win in four games.
The Blue Devils (12-4, 1-2 ACC), meanwhile, dropped a second in three contests despite 20 points from Rodney Hood.
Jabari Parker added 15 points and seven rebounds for Duke.
Celebrity Couples of 2014 [PHOTOS]