The Potomac Highlands include Grant, Hampshire, Hardy, Mineral, and Pendleton counties in West Virginia, and neighboring areas of Maryland and Virginia. The West Virginia counties are the mountainous uplands of the Eastern Panhandle, drained by the Potomac headwaters. The western edges of Grant and Mineral counties lie west of the Allegheny Front and are a part of the Allegheny Mountains. All the other territory is east of the Allegheny Front and a part of the Ridge and Valley system.

Within West Virginia's Potomac Highlands, a region of 2,722 square miles, are many of our state's most spectacular mountain features. They include Spruce Knob (4,861 feet), the state's highest point. Other features of renown include Seneca Rocks, the Trough, Lost River, and the Smoke Hole. The dominant vegetation of the Potomac Highlands is forest, with regrowth northern hardwoods at the lower levels and spruce and pine at the higher elevations.

Elevation has a direct effect on temperature and precipitation. Cool to cold winters and warm summers are normal throughout the Potomac Highlands, but the precipitation varies greatly. Annual snowfalls of 60 to 100 inches occur in some mountain areas. Some mountain areas and western slopes receive an annual rainfall of as much as 70 inches, but many parts of the Potomac Highlands lie within the "rain shadow" east of the Alleghenies. In the South Branch Valley rainfalls of 30 to 35 inches yearly are typical.

Archeological remains show that the Potomac Highlands region was inhabited in prehistoric times. The earliest known inhabitants occupied the Potomac Valley and subsisted on a livelihood of hunting and gathering. As their culture advanced, a more settled lifestyle based on agriculture evolved, but the Native population was never very large in the Highlands. Their legacy remains in names, mounds, village sites, and trails.

Terrain conditions influenced the colonial and post-colonial settlement and occupancy of the Potomac Highlands. Hampshire was the first county of present West Virginia, formed in 1753. Grant and Mineral counties were not organized until 1866. The 2020 population of the Potomac Highlands was 81,449. The people are mostly rural nonfarm residents, with Keyser (population 4,853 in 2020) the largest urban place in the region. Agriculture (especially poultry and livestock), tourism, forestry products, and manufacturing are the primary economic pursuits in the Potomac Highlands.