Duke put together two overwhelming runs in the first half and needed fewer than 18 minutes to build a 30-point lead.
Richard Howell had a career-high 18 points for the Wolfpack (12-11, 2-7), who had 16 turnovers and didn't get closer than 21 in the second half. They lost their fourth straight and seventh in eight games, and dropped into 11th place in the league standings.
Seth Curry had 13 points for the Blue Devils, who tuned up for the latest renewal of college basketball's fiercest rivalry - Wednesday night's showdown with No. 23 North Carolina - and extended their winning streak at Cameron Indoor Stadium to an NCAA-best 32 by making quick work of another neighboring rival.
Smith, who's on pace to become the first player in ACC history to lead the league in scoring and assists, finished with seven assists for Duke and had his league-best 13th 20-point game.
In essentially sealing this one by halftime, the Blue Devils shot 64.5 percent in the half and made nearly as many shots (20) as the Wolfpack attempted (25).
The reigning national champions broke it open with a 21-2 burst midway through the half in which they scored 14 consecutive points - including a personal 6-0 run by Plumlee - and took their first 20-point lead on Curry's jumper that made it 31-10 with 8 1/2 minutes left.
And they weren't finished. Duke assembled a 16-2 run a few minutes later keyed by 3s from Smith, Curry and Singler, who also hit a free throw to make it 51-21 with 2:11 before the break.
Lorenzo Brown had 15 points and DeShawn Painter added 10 for the Wolfpack. They've lost 13 straight against Duke at Cameron - with 11 of those decided by double digits - and haven't won a game on an opponent's regular home court this season.
N.C. State played without freshman big man C.J. Leslie, the team's leading rebounder and third-leading scorer who was suspended for violating an unspecified team rule.
Howell picked up some extra minutes in his absence and scored 10 of the Wolfpack's first 12 points, but that wasn't nearly enough to keep them in it. With roughly 8 minutes left in the half, the rest of the team was 1 for 10 and N.C. State trailed by 19 with more turnovers (seven) than field goals (six).