PA 645 begins at an intersection with
US 422 at the north edge of the borough of
Myerstown in
Lebanon County, where North Locust Street heads south into Myerstown. From this intersection, the route heads north on two-lane undivided North Locust Street into
Jackson Township, passing near residential neighborhoods. PA 645 runs through agricultural areas with some homes, curving northwest briefly before turning north again onto Kutztown Road. The road passes through the residential community of Kutztown before it heads back into farmland. The route turns east onto East Rosebud Road before it heads north onto Hilltop Road, passing through a mix of farms and residential development and curving northwest. The route enters
Tulpehocken Township in
Berks County and becomes Camp Swatara Road, running north-northwest through agricultural areas with some homes and commercial development. PA 645 crosses the
Little Swatara Creek into
Bethel Township, where it turns north. The road passes through the residential community of
Frystown, where it intersects Frystown Road, before running through more farmland. The route passes near businesses and comes to an interchange with
I-78/
US 22. Past this interchange, the road heads through farmland and woodland with some homes. PA 645 turns to the west and enters forested areas, where it begins to ascend
Blue Mountain. The route turns to the north and continues to climb the mountain, heading to the northeast. At the summit of Blue Mountain, PA 645 crosses the
Appalachian Trail and heads into
Pine Grove Township in
Schuylkill County. At this point, the name becomes Geary Wolf Road and the road winds north to descend the forested mountain. At the bottom of the mountain, the route heads through a mix of farmland and woodland with some homes, passing through the community of Brookside. PA 645 passes near residences and an industrial park, crossing
Swatara Creek before it reaches its northern terminus at an intersection with
PA 443 south of the borough of
Pine Grove. ==History==