Caleb Daniels and Collin Gillespie had 11 each for the Wildcats (23-7, 16-4 Big East), who already had clinched the #2 seed in the upcoming Big East conference tournament. Jordan Longino also scored 10 and reached double figures for the first time in his career.
Chuck Harris led Butler (13-18, 6-14) with 19 points and Bo Hodges added 12.
The Bulldogs, who shot just 5 of 25 from beyond the 3-point arc, finished the regular season with a five-game losing streak.
Longino dropped in consecutive 3-pointers and Villanova went ahead 23-4 with 10:51 left in the first half. The second trey capped a 20-1 run for the Wildcats.
Butler went more than six minutes without a field goal.
Samuels drove to the basket and threw down a one-handed dunk for a 25-9 advantage with 8:35 remaining.
Harris was 4 of 6 from the field, but the rest of the Bulldogs struggled mightily (6 of 23) and trailed 32-15 with less than four minutes to go in the first half. The frustration became evident as usually mild-mannered Butler head coach LaVall Jordan was whistled for a rare technical foul.
Villanova led 38-24 at halftime thanks in large part to Samuels' 11 points.
Butler shot just 10 of 29 in the opening half.
Brandon Slater and Moore hit consecutive shots on the Wildcats' first two possessions of the second half as they quickly extended their lead to 18.
Hodges finally snapped a cold shooting streak with a layup.
But Moore responded with a deep 3-pointer for a 45-26 advantage with 16:15 remaining.
Villanova tightened defensively and moved ahead 54-30 when Chris Arcidiacono dropped in two free throws with 12:09 left.
Butler continued to misfire while Slater and Gillespie knocked down 3-pointers and the Wildcats led 60-32.
Villanova breezed to the victory from there.