Jon Scheyer had 20 points and five steals for the Blue Devils (25-4, 12-2 ACC), who have won eight straight.
Duke visits Maryland on Wednesday in what will go a long way in deciding the ACC regular season crown.
Jerome Meyinsse had 21 points and seven rebounds for the Cavaliers (14-13, 5-9), who have dropped seven straight games.
The Blue Devils held the lead from the beginning as the team scored 10 of the first 12 points with Scheyer's three-ball making it a 10-2 game a bit over four minutes in.
After Meyinsse put in a jumper for Virginia, Duke scored the next 10 points for a 20-4 lead on a Singer three-point play.
The Blue Devils led by as many as 17 points in the first half and took a 35-21 lead into the break.
Virginia didn't get its first field goal until five minutes into the second half, and by that point Duke had an 18-point lead.
From that point Duke continued to hold onto a significant lead as it cruised to the finish line.
Virginia plays at Boston College on Wednesday...Duke owns a commanding 111-48 series lead over Virginia...Duke shot 48 percent in the game while Virginia made just 31.4 percent of its shots.