Greensboro Road, William F. Stone Highway, Virginia Avenue, Virgil H. Goode Highway, Franklin Road, Roanoke Road, Botetourt Road, Market Avenue, Grafton Street, East Madison Street, North Alleghany Avenue, Hot Springs Road, Ingalls Boulevard, Stuart Highway, Jackson River Road, Potomac River Road

Southern Terminus:
North Carolina-Virginia state line
Northern Terminus:
Virginia-West Virginia state line
186.87 miles
Henry, Franklin, Roanoke, Botetourt, Alleghany, Bath, Highland
Independent Cities:
Roanoke, Covington

US 220 is a north/south route extending from Rockingham, North Carolina, to South Waverly, Pennsylvania, along the border with New York. It enters Virginia from North Carolina south of Martinsville and is at first known as Greensboro Road. After a few miles, it has an interchange with the William F. Stone Highway (US 58), a semicircular highway around Martinsville. The two routes are multiplexed for a few miles. Then, US 58 splits off while US 220 continues to follow the highway north to where it ends in Bassett Forks. The highway peters out, and US 220 continues north as a surface road to Roanoke.

In Roanoke, US 220 becomes a highway again. It is multiplexed with I-581 for its entire length to where it ends at I-81. It then follows I-81 for a couple of exits north and then splits off to become a surface road again. It runs north to Clifton Forge, where it follows Grafton Street (Business US 60) north for a few blocks to I-64. US 220 is multiplexed with I-64 to the west from Clifton Forge to Covington. From there, it heads north into the mountains and then up to Monterey. A few miles north of Monterey, it crosses the border into West Virginia.

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