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.

Perry County is a county located in the southeastern portion of the U.S. state of Missouri. As of the 2020 census, the population was 18,956. Its county seat is Perryville. The county was officially organized on November 16, 1820 from Ste. Genevieve County and was named after Oliver Hazard Perry, a naval hero of the War of 1812.