Some sources and regional associations only identify the eastern panhandle as being composed of Morgan, Berkeley, and Jefferson Counties.

Berkeley, Hampshire, Hardy, Jefferson, and Morgan Counties were part of the Unionist state of West Virginia created in 1863.

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

The eastern panhandle includes West Virginia's oldest chartered towns (1762) of Romney and Shepherdstown.

Until 1861 Harpers Ferry was the site of a U.S. armory (weapons factory), briefly captured by John Brown during his famous raid.

There has been talk about certain counties in the eastern panhandle rejoining Virginia, due primarily to poor economic conditions and perceived neglect from the state government.

In July 2005, the United States Census Bureau released a list of the top 100 counties according to housing growth.