Interstate 581 (I-581) is a spur of I-81 into Roanoke, Virginia, completely overlapping US Route 220 (US 220). It is planned to be connected to I-73. Future I-73 Corridor signs are marked on I-581 on the southbound side just after exit 2.

Interstate 81 (I-81) is an 855.02-mile-long (1,376.02 km) Interstate Highway. In the US state of Virginia, I-81 runs for 324.92 miles (522.91 km), making the portion in Virginia longer than any other state's portion of the route. It is also the longest Interstate Highway within the borders of Virginia. It stretches from the Tennessee state line near Bristol to the West Virginia state line near Winchester. It enters Virginia from Bristol, Tennessee, and leaves Virginia into Berkeley County, West Virginia. The route passes through the cities of Bristol, Roanoke, Lexington, Staunton, and Harrisonburg.