Immediately past the New River, the freeway becomes the border between Montgomery County to the southeast and the independent city of Radford to the northwest, where it interchanges with SR 232/SR 605. From this point, I-81 fully enters Montgomery County, coming to rest areas in both directions prior to an interchange with SR 177/SR 600, which also provides access to Radford University.
Following its passage over the New River, the highway becomes a dividing line between two areas: Montgomery County to the southeast and the independent city of Radford to the northwest. It then merges with SR 232/SR 605 before entering Montgomery County in full, where it has rest stops on both sides before intersecting with SR 177/SR 600, which also serves Radford University.