New Madrid County is a county located in the Bootheel of the U.S. state of Missouri. As of the 2020 census, the population was 16,434. The largest city is Portageville and county seat is New Madrid, located on the northern side of the Kentucky Bend in the Mississippi River, where it has formed an oxbow around an exclave of Fulton County, Kentucky. This feature has also been known as New Madrid Bend or Madrid Bend, for the city.

The Missouri Bootheel is a salient (protrusion) located in the southeasternmost part of the U.S. state of Missouri, extending south of 36°30′ north latitude, so called because its shape in relation to the rest of the state resembles the heel of a boot. Strictly speaking, it is composed of some or all of the counties of Dunklin, New Madrid, and Pemiscot. However, the term is locally used to refer to the entire southeastern lowlands of Missouri located within the Mississippi Embayment, which includes parts of Butler, Mississippi, Ripley, Scott, Stoddard and extreme southern portions of Cape Girardeau and Bollinger counties. The largest city in the region is Kennett.