Pennsylvania Route 645 is a state highway in the Commonwealth of Pennsylvania. The route runs from U.S. Route 422 in Myerstown, Lebanon County north to Pennsylvania Route 443 in Pine Grove Township, Schuylkill County.

Pennsylvania Route 645 heads north from US 422 on North Locust Street into Jackson Township. The name changes to Kutztown Road a short distance north of US 422. Pennsylvania Route 645 then heads east for a short distance on East Rosebud Road before turning north on Hilltop Road. It crosses into Bethel Township in Berks County where the name changes to Camp Swatara Road. It features an interchange with Interstate 78/U.S. Route 22 near Frystown and then crosses the Blue Mountain range into Pine Grove Township, Schuylkill County and the road name becomes Geary Wolf Road. Pennsylvania Route 645 then continues north to Pennsylvania Route 443 just south of the borough of Pine Grove.