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The Potomac Highlands of West Virginia are the root of the Eastern Panhandle, bordering Maryland and Virginia. They comprise the following counties: Grant Hampshire Hardy Mineral Pendleton Because of geographical proximity and shared culture and history, the Potomac Highlands region is often extended to include Pocahontas, Randolph, and Tucker Counties, even though they are not within the Potomac River watershed.

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The Potomac Highlands includes West Virginia's oldest town (1762) of Romney.

The Potomac Highlands also includes West Virginia's oldest county: Hampshire (1753).

West Virginia's highest elevation above sea level is located in the Potomac Highlands in Pendleton County: Spruce Knob, 4,863 feet (1,482 meters).

Shortly after West Virginia gained statehood, Mineral and Grant counties were created from Hampshire and Hardy in 1866.