Wytheville sits precisely at the junction of I-77 and I-81, which makes it one of the most easily reached small towns in Virginia — and explains why so many interstate travelers stop here. By car from Roanoke it's about 90 minutes southwest on I-81; from Charlotte, North Carolina it's 2.5 hours north on I-77; from Washington DC it's approximately 4 hours southwest, again on I-81. The town is a natural midpoint on several common routes through the southern Appalachians.
There is no Amtrak service to Wytheville, and the nearest commercial airport of any size is Roanoke-Blacksburg Regional (ROA), about 90 minutes away. This is, straightforwardly, a road-trip destination. The interstate access is so direct that the town functions partly as a rest and fuel stop for long-distance drivers — but there's enough to see for an overnight or a focused half-day if you plan it. The downtown is compact enough that you can park once and cover everything on foot.