Montrezl Harrell scored 17 points to lead the Cardinals (10-1), who have not lost since Nov. 24 and shot 51.5 percent as a team on Tuesday.
Harrell hit 6-of-8 shots from the field and nabbed eight rebounds. Russ Smith, Terry Rozier and Wayne Blackshear each scored 11 points.
Jamar Gulley scored 14 for Missouri State (8-2) and was the only member of the Bears to reach double figures. Missouri State shot a modest 37.9 percent from the field and went 4-for-15 from 3-point range.
Louisville led 47-24 at halftime and won the rebounding battle 50-31.