Devin Ebanks added 16 for West Virginia, which led 52-34 at halftime.
Corey Fisher had 17 points to lead Villanova (20-5, 8-4), which had its six-game winning streak snapped. Corey Stokes and Scottie Reynolds added 12 each.
Stokes hit a 3-pointer with 3:53 to play to pull the Wildcats within 13. The Mountaineers responded with a 7-0 run, capped by Butler's sixth 3 to extend the lead to 20 points and seal the win.
Butler became the first West Virginia player to score 40 points in a game since Lowes Moore in a win over Notre Dame in 1978.
The Mountaineers, who beat a team in the top half of the conference standings for the first time this season, topped their previous high of 92 points in wins over Elon. and Seton Hall. West Virginia also ended Villanova's streak of three consecutive games with at least 90 points.
Former WVU star Joe Alexander, who led the Mountaineers to the regional semifinals of the NCAA tournament last year, was seated behind the Mountaineer bench. Alexander was drafted eighth overall by the Milwaukee Bucks in last June's NBA draft.
