The Spartans became the first No. 1 seed to exit the tournament, doing so in the semifinals of the West Region.
Louisville limited Michigan State to 28 percent shooting and just 14 field goals for the game. The Cardinals will meet Florida Saturday in the regional finals in a matchup of teams seeded fourth and seventh.
The Cardinals forced 15 turnovers and had nine steals, three of them coming from Behanan. He hit 6-of-10 from the floor, becoming one of only two players in the game to make at least half his shots.
Michigan State's starters went 12-of-40 from the field.
Louisville took control with a brief 8-2 run early in the second half that put the Cardinals in front by eight. Michigan State scored just three points over the final 3:30 of the contest.
Russ Smith added 11 points for the Cardinals (29-9). They lost their final two regular-season games, but have now won seven in a row -- four en route to the Big East Conference Tournament title and three more in the NCAA tourney.