Cape Girardeau County is located in the southeastern part of the U.S. state of Missouri; its eastern border is formed by the Mississippi River. At the 2020 census, the population was 81,710. The county seat is Jackson, the first city in the US to be named in honor of President Andrew Jackson. Officially organized on October 1, 1812, the county is named after Ensign Sieur Jean Baptiste de Girardot, an official of the French colonial years. The "cape" in the county's name is named after a former promontory rock overlooking the Mississippi River; this feature was demolished during railroad construction. Cape Girardeau County is the hub of the Cape Girardeau–Jackson metropolitan area. Its largest city is Cape Girardeau.

Jackson is a city in and the county seat of Cape Girardeau County, Missouri, United States. It is a principal city of the Cape Girardeau–Jackson, MO-IL Metropolitan Statistical Area. The population of Jackson was 15,481 at the 2020 census.