East of the village of Glengary, the state highway crosses Back Creek then veers northeast to ascend North Mountain.

WV 45 descends into the Shenandoah Valley, passing the community of Union Corner and the historic homes Campbellton and Ar-Qua Springs.

[1] WV 45 intersects I-81 at a diamond interchange and continues east as Apple Harvest Drive, a four-lane undivided highway that passes through a commercial area south of the city limits of Martinsburg where the highway meets a Winchester and Western Railroad line at grade and intersects US 11 (Winchester Avenue).

US 11 joins the two state-numbered highways on Queen Street past the Apollo Theatre and near the Martinsburg station, which serves Amtrak's Capitol Limited and is the western terminus of MARC's Brunswick Line.

The state highway passes through the hamlet of Files Crossroad and enters Jefferson County at Rockymarsh Run just north of Wynkoop Spring.