The river that forms part of the eastern boundary of the Appalachian region is the Potomac River.

The Potomac River flows along the eastern edge of the Appalachian Mountains, serving as a natural boundary between several states, including West Virginia, Virginia, and Maryland. This river is significant not only for its geographical importance but also for its historical and cultural value, as it has played a vital role in the development of the surrounding regions. The Potomac River provides recreational opportunities and serves as an important waterway for transportation and commerce, linking various communities within the Appalachian area.