Mouth of Wilson is an unincorporated community, in Grayson County in the U.S. state of Virginia, just north of the North Carolina state line. The community lies in the Blue Ridge Highlands section of the Blue Ridge Mountains which are part of what is considered the 'Middle Appalachian Mountains' on the western banks of the New River, where the Big Wilson Creek empties its waters. The main road through the area is U.S. Route 58; other major roads include Virginia Route 16 and Virginia Route 93 (County Line Road).