Interstate 81 (I-81) in the US state of West Virginia crosses the Eastern Panhandle region, linking Virginia to Maryland. The Interstate Highway, completed in 1966, spans 26 miles (42 km) through Berkeley County, paralleling U.S. Route 11 (US 11) for its entire length. I-81 enters the state near Ridgeway, travels northeast, bypassing the city of Martinsburg, and leaves the state at the Potomac River, which serves as the state line. The first solicitations for the construction of I-81 were published in 1959, with the first six miles (9.7 km) of freeway being opened in 1963, and the full length was completed by 1966. On average, between 45,000 and 60,000 vehicles use the freeway through the panhandle per day.

Berkeley County is located in the Shenandoah Valley in the eastern panhandle region of West Virginia in the United States. The county is part of the Hagerstown–Martinsburg metropolitan area. As of the 2020 census, the county population was 122,076, making it the second-most populous of West Virginia's 55 counties, behind Kanawha County. The City of Martinsburg is the county seat.