Roanoke is served by a comprehensive network of State and Federal roads, placing half of the U.S. population within a 12-hour drive of the City. Major routes through Roanoke include:
- I-581/I-81 – Dandridge, Tennessee to the Canadian border at Wellesley Island, New York.
- U.S. 460 – Norfolk, Virginia to Frankfort, Kentucky.
- U.S. 221 – Lynchburg, Virginia to Perry, Florida.
- U.S. 220 – Rockingham, North Carolina to Waverly, New York.
- U.S. 11 – New Orleans, Louisiana to the Canadian Border at Rouses Point, New York.
- FUTURE I-73 – proposed to connect Sault St. Marie, Michigan to Myrtle Beach, South Carolina.