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Cape Girardeau County was organized on October 1, 1812, as one of five original counties in the Missouri Territory after the US made the Louisiana Purchase of 1803. It is named after Ensign Sieur Jean Baptiste de Girardot (also spelled Girardeau or Girardat), a French officer stationed 1704–1720 at Kaskaskia in the Illinois Country of New France. In 1733 he founded a trading post on the Mississippi River, which developed as the present-day city of Cape Girardeau. The "cape" in the county name was a rock promontory overlooking the Mississippi River and Claire's house; the original cape rock was destroyed by railroad construction.
Jackson, Missouri is the county seat. The first Cape Girardeau County Courthouse was constructed in 1818 by John Davis. This courthouse burned in 1870. The present courthouse in Jackson was completed in 1908 and was designed by P.H. Weathers.
The county is the site of one of the oldest cold cases in the state of Missouri. Bonnie Huffman, a 20-year-old schoolteacher, was found murdered in a ditch just outside Delta on July 2, 1954. Her case was never solved.
Cape Girardeau is referenced in Dave Van Ronk's song "Hang Me, Oh Hang Me," which has found a place in the folk canon since its release in 1962. The song was featured prominently in the 2013 film Inside Llewyn Davis. In the second verse, the singer refers to having "been all around Cape Girardeau and parts of Arkansas...poor boy, I've been all around this world."
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