Smith had 12 in the first half for the Cardinals (11-1), who never trailed and were rarely threatened, outside of a couple brief early stretches where the game was tight.
Tymell Murphy scored 16 points and former Louisville player Rakeen Buckles added 13 for FIU (8-5), which was coached last season by Richard Pitino, the son of Louisville coach Rick Pitino.
Rick Pitino decided to honor the contract and play FIU, offering to do so in Miami even after his son left the Panthers to take over at Minnesota after last season. When Richard Pitino left FIU, Louisville had the option of canceling the series.
"But they wanted to give us the game and we're very appreciative," FIU director of sports and entertainment Pete Garcia said.
There were plenty of potential pratfalls that could have grabbed at Louisville in this one.
First, it absolutely was the biggest game of FIU's season, considering the Panthers are ineligible for any postseason appearance because of academic sanctions.
The Cardinals had to avoid slipping into vacation mode, which likely wasn't easy since they checked into an upscale Miami Beach resort on Wednesday and aren't leaving until Monday.
Christmas is looming and when Louisville gets past that, the rivalry game against Kentucky awaits on Dec. 28.
There was no looking ahead, not to the holiday and not to Kentucky, either. From the outset, Louisville was all business.
Louisville opened the game on a 10-3 run, setting a tone where the Cardinals would only have to flex their muscle in short spurts to assert control. FIU scored the next six points, but the next Louisville run restored order in a hurry.
Montrezl Harrell, who finished with 10 points, had an alley-oop that left the basket shaking for a full 15 seconds afterward, a play that started a 12-0 run by the Cardinals and turned a 10-9 edge into a 22-9 gap.
FIU settled down and back-to-back 3-pointers by Buckles and Dennis Mavin got the Panthers within 30-25 late in the half. But the Cardinals had one last first-half flurry in them, ripping off the last nine points and capping that spurt with another alley-oop dunk by Harrell with just over a second remaining.
That sent Louisville into the locker room with a 39-25 lead, and there was no doubt from there.