The Potomac River flows into the Chesapeake Bay, located along the mid-Atlantic coast of the United States. The river is approximately 383 statute miles (616 km) long, with a drainage area of about 14,700 square miles (38,000 km²). In terms of area, this makes the Potomac River the fourth largest river along the Atlantic coast of the USA and the 21st largest in the USA. Over 5 million people live within the Potomac watershed, where precipitation provides the equivalent of over 8 m³ (more than 2,100 US gallons) of water per person per year.

The source of the North Branch Potomac River is at the Fairfax Stone located at the junction of Grant, Tucker and Preston counties in West Virginia.

From the Fairfax Stone, the North Branch Potomac River flows 27 miles (43 km) to the man-made Jennings Randolph Lake, an impoundment designed for flood control. Below the dam, the North Branch cuts a serpentine path through the eastern Allegheny Mountains. First, it flows northeast by the communities of Bloomington, Luke, and Westernport in Maryland and then on by Keyser, West Virginia to Cumberland, Maryland. At Cumberland, the river turns southeast. It is joined by the South Branch between Green Spring and South Branch Depot, West Virginia from whence it flows past Hancock, Maryland and turns southeast once more on its way toward Washington, D.C., and the Chesapeake Bay.