The New Madrid Seismic Zone (NMSZ), sometimes called the New Madrid Fault Line, is a major seismic zone and a prolific source of intraplate earthquakes in the Southern and Midwestern United States, stretching to the southwest from New Madrid, Missouri.

New Madrid is a city in New Madrid County, Missouri, United States. The population was 2,787 at the 2020 census. New Madrid is the county seat of New Madrid County. The city is located 42 miles (68 km) southwest of Cairo, Illinois, and north of an exclave of Fulton County, Kentucky, across the Mississippi River.