Madison County is a county located in the Lead Belt region of the U.S. state of Missouri. As of the 2020 census, the population was 12,626. Its county seat and largest city is Fredericktown. The county was officially organized on December 14, 1818, and was named after President James Madison.

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 in Rolla.