- I-81 runs through the Roanoke Region with direct connections to I-64 to the north and I-77 to the south, providing convenient access to major markets.
- I-40, a major east-west interstate running through the south-central portion of the United States, is 47 miles from the region.
- Freight rail service is provided by CSX Transportation and Norfolk Southern.
- Passenger rail service is provided by Amtrak from downtown Roanoke, providing daily trains to and from Washington, D.C., New York, and beyond.
- The Virginia TradePort, located at the New River Valley Airport in Dublin, is 44 miles south, and The Port of Virginia in Hampton Roads is 182 miles east of the region.
- Roanoke-Blacksburg Regional Airport (ROA) offers commercial air service, served by four airlines with approximately 40 arriving and departing flights per day and nonstop service to eight cities, as well as frequent connecting service.