The major fault line located near the Appalachian Mountains is the New Madrid Fault.

The New Madrid Fault system is situated in the central United States, primarily in southeastern Missouri and northeastern Arkansas, but it extends into parts of the Appalachian region. This fault line is known for a series of significant earthquakes that occurred in the early 19th century, specifically from 1811 to 1812. While it is not directly within the Appalachian Mountains, its proximity means that seismic activity from the New Madrid Fault can potentially affect areas in and around the Appalachians.