The Wildcats (15-1 overall, 3-1 Big East) shot 53.6 percent from the field and 44.8 percent from 3-point range against the Blue Demons (9-8, 3-1), who came into the contest alone in first place in the conference after three surprising wins.
Villanova made a season-high 13 3-pointers on 29 attempts, with Hilliard and Arcidiacono leading the way with four apiece.
JayVaughn Pinkston added nine points and six rebounds for the Wildcats, who outscored DePaul 30-10 in the paint.
Tommy Hamilton led the Blue Demons with 12 points and Darrick Wood added 10.
The Wildcats, whose only loss of the season came last week at Seton Hall, quickly showed why they were the preseason choice to win the Big East while DePaul was picked last.
Villanova reeled off a 13-0 run to take a 16-5 lead with just under 12 minutes remaining in the first half. The spurt began with back-to-back 3-pointers from Hilliard and was capped by a ferocious one-handed slam from center Daniel Ochefu.
The Wildcats boosted their lead to 24-9 and surged to a 37-14 advantage with three minutes left on a quick 11-0 run spurred by consecutive Arcidiacono 3-pointers.
Villanova made its final eight shots of the first half, capped by Arcidiacono's buzzer-beating jumper after Ochefu tapped out a pass by Josh Hart from the opposite baseline.
The Wildcats led by as many as 34 points in the second half before emptying their bench at the final TV timeout.
TIP-INS
DePaul: The Blue Demons have lost 49 straight games to ranked opponents. Their last win over a ranked opponent came against Villanova on Jan. 3, 2008. . DePaul finished with 15 turnovers and seven assists.Villanova: The Wildcats have won nine straight meetings against DePaul and hold a 19-8 advantage in the series. . Villanova shot 62 percent from the floor in the first half and 58 percent from 3-point range.
UP NEXT
DePaul: hosts Georgetown on Tuesday.Villanova: hosts Xavier on Wednesday.