Behanan matched his career best in the first half with 13, outrebounding the Bulldogs (12) by himself.
Gorgui Dieng had 10 points and 13 rebounds while Wayne Blackshear added 13 points with five rebounds as the Cardinals (2-0) won the opener of the Battle 4 Atlantis tournament that continues next week in the Bahamas.
Louisville never trailed in its first meeting against Samford (1-2), which was playing its highest ranked opponent since losing 79-54 to No. 1 and defending champion Florida in 2006.
Tim Williams' 15 points and six rebounds led Samford. Raijon Kelly added 11 for the Bulldogs, who committed 21 turnovers and were outrebounded 53-28.
"The first half, I thought we had a little stage fright," Samford coach Benny Seltzer said.
Smith led the Cardinals in scoring for the second straight game. He scored a game-high 23 in Sunday's season-opening 79-51 victory over Manhattan, including four 3-pointers.
Louisville, which concludes its homestand Sunday against Miami (Ohio), needs these kinds of tuneups to prepare for tougher competition when it resumes the Battle 4 Atlantis on Thursday against Northern Iowa.
The Panthers are part of a field that includes No. 9 Duke, No. 14 Missouri and No. 17 Memphis.
Coach Rick Pitino said he wanted to use these games to try different things to prepare his team. He started with Thursday night's starting lineup.
Louisville's initial set included sophomores Behanan and Blackshear at forward along with Peyton Siva, Luke Hancock and Dieng. On Sunday, those two came off the bench for Montrezl Harrell while Smith began at guard.
The Cardinals also tried a smaller lineup with Dieng surrounded by three guards and Hancock.
All the combinations were effective as the Cardinals built a 24-6 lead after 11-plus minutes, helped by a 13-0 run. They had outrebounded the Bulldogs 11-4 at that point and made it hard for Samford to get anything inside.
Louisville closed the half even better, holding Samford without a field goal for the final 7:08 to lead 42-13 at intermission.
In fact, the Bulldogs didn't crack double digits until 4:38 remained in the half when Clide Geffrard Jr. made two free throws.
Samford had as many free throws (four) as field goals during a half in which it shot 22 percent.
Louisville enjoyed a solid start, spreading the ball around on offense while dominating the boards.
The Bulldogs were more effective in the second half, hitting eight 3-pointers but couldn't get closer than 24 points.
"I'm proud of our second half, but we must become a tougher team," Seltzer said.