Route 51 is a highway in southeastern Missouri.

Its northern terminus is the Illinois state line near Chester, Illinois; its southern terminus is at the Arkansas state line northwest of Piggott, Arkansas.

Route 51 is one of the original 1922 state highways and ran from the Mississippi River to Advance.

Route 51A would become part of the main highway when it was re-routed and extended.

This Missouri road-related article is a stub.