Indianapolis, IN – Kyle Kuric scored 17 points, Chris Smith 53, on Saturday.
Louisville (3-0) didn't take its first lead until the final seconds before halftime. It used an 11-2 run in the second half to pull away for the 16-point win.
Khyle Marshall scored 20 points to lead Butler (1-2) and Chase Stigall added 11.
The Cardinals were the highest-ranked team to play on Butler's home court since 1992, when No. 5 North Carolina raced past the Bulldogs, 103-56.