The score was tied 79-79 when Arcidiacono drove the left side and banked home a go-ahead lay-in, drawing a foul from Kadeem Batts.
His subsequent foul shot gave him 21 points for the game and lifted the Wildcats (23-3, 11-2 Big East) to a hard-earned victory.
JayVaughn Pinkston supplied 20 points with six rebounds and James Bell chipped in 17 and nine for Villanova.
The Friars (17-10, 7-7) were led by Bryce Cotton with 22 points, nine assists and seven rebounds.
Batts finished with 21 points and 11 rebounds.