State Route 65, formerly State Route 66, is a primary state highway in the U.S. state of Virginia. The state highway runs 34.06 miles (54.81 km) from U.S. Route 23, US 58, and US 421 in Clinchport north to US 58 Alternate in Castlewood.

U.S. Route 23 (US 23) is a part of the United States Numbered Highway System that runs from Jacksonville, Florida, to Mackinaw City, Michigan. In Virginia, the U.S. Highway runs 60.80 miles (97.85 km) from the Tennessee state line near Weber City north to the Kentucky state line near Pound. US 23, which is known as Orby Cantrell Highway for most of its course, is a four-lane divided highway that follows Corridor B of the Appalachian Development Highway System through Southwest Virginia. The U.S. Highway serves as the main east–west highway of Scott County and the primary north–south highway of Wise County. US 23 runs concurrently with US 58 from Weber City to Duffield and with US 58 Alternate between Big Stone Gap and the independent city of Norton.