The game was part of the Battle 4 Atlantis Tournament, which will continue next week in the Bahamas.
Louisville limited Samford to only four field goals in the first half while racing to a 42-13 lead.
Smith saw plenty of playing time in the second period while making 7-of-14 shots from the field.
Wayne Blackshear scored 13 points while Chane Behanan had 12 points and 18 rebounds for the Cardinals (2-0).
Samford (1-2) committed 21 turnovers and was led in scoring by Tim Williams with 15 points.