The Cardinals remained unbeaten in eight games, but were not able to break away until a Smith-led surge early in the second period. Louisville had only a 50-45 lead with 14:07 remaining, and then went on a 22-4 run to crush the Jaguars.
Smith scored 12 of his 19 points during that stretch. Gorgui Dieng added 18 points and 12 rebounds for the Cardinals, who began the evening as one of 14 unbeaten teams remaining in major college basketball.
Dieng hit all eight of his field goal attempts and Louisville shot 55 percent as a team.
Stephen Thomas scored 14 points to lead IUPUI.
Celebrity Families of 2014 [PHOTOS]