Route 22 is a highway in central Missouri. Its eastern terminus is at Route 15 in Mexico; its western terminus is at U.S. Route 63 south of Clark on the Randolph/Boone county line. Route 22 was one of the original 1922 state highways and originally had an eastern terminus at Route 9 (now U.S. Route 61) in Louisiana. This section was replaced by U.S. Route 54 in 1926.