Kyle Singler added 20 points for the Blue Devils (11-1), who took control of the game early en route to their fifth straight victory. Duke led by double figures in the first 5 minutes, then ran off a 23-3 run that blew the game open and turned the rest of the contest into a formality.
It was a good way for Duke to head into Sunday's ACC opener against Clemson, which hasn't won at Cameron Indoor Stadium since 1995. The Blue Devils shot 60 percent, hit 10 of 21 3-pointers and finished with a season-high scoring output to extend the Quakers' miserable start.
It was a record day for all the wrong reasons for Penn (0-9). Duke's 114 points were the most by an opponent, while the 59-point margin of defeat was also the worst in program history.
Jack Eggleston scored 13 points to lead Penn, which has lost both games since Glen Miller was fired and Jerome Allen took over as interim coach.
The Quakers opened the game with a 3-pointer and scored again a minute later, but little went right after that. They went 8½ minutes without a field goal — with several shots going halfway down before rattling out or rolling all the way around the cylinder before dropping harmlessly off the rim — while the Blue Devils had no such offensive troubles.
Smith buried a jumper from the left corner to make it 16-6 early in the Quakers' drought. A few minutes later, Miles Plumlee's dunk started a run of 11 straight scoring possessions for the Blue Devils, who got 3s from Jon Scheyer and Andre Dawkins before Brian Zoubek's inside score pushed the lead to 40-11 with 8:30 left before halftime.
Penn played the Blue Devils even the rest of the half and trailed 58-29 at the break, though Allen — frustrated by several borderline calls that went against the Quakers — picked up a technical foul for arguing with officials.
Things were no better in the second half, with Duke steadily increasing the margin and cracking the 100-point mark on a free throw from freshman Mason Plumlee with 5:42 to play.
Scheyer finished with 19 points and a career-high 11 assists for the Blue Devils, while Plumlee finished with a season-high 18 points. It was Duke's national-best 76th straight nonconference home win and its 36th consecutive home victory against an unranked opponent.
The game drew Oscar-winning actor Denzel Washington, whose son, Malcolm, is a freshman walk-on for the Quakers. Washington kept a low profile in college basketball's notoriously hostile arena, wearing a dark blue Penn hat and sitting a couple of rows behind the scorer's table near the Penn bench.
He did, however, acknowledge the Cameron Crazies by tipping his hat after they started chanting his name during a second-half timeout with the Blue Devils leading by 40 points.