Route 72 is a highway in southern Missouri. Its eastern terminus is at Route 34 west of Jackson; its western terminus is at I-44 on the exit with U.S. Route 63 in Rolla.

Route 72 is one of the original 1922 state highways. Its eastern terminus was at Centerville, and its western terminus was at the junction with Route 32. The part between Arcadia and Fredericktown was Route 70 from 1922 to 1959, when it became part of Route 72 because of I-70.