PA 372 begins at an intersection with PA 74 in Lower Chanceford Township, York County, heading northeast as two-lane undivided Holtwood Road. The route heads through wooded areas with some farmland and comes to the Norman Wood Bridge over the Susquehanna River, located to the south of Holtwood Dam. Upon crossing the river, PA 372 enters Martic Township in Lancaster County and passes over Norfolk Southern's Port Road Branch as it continues into forested areas. The road turns north as it passes to the west of the Muddy Run Pumped Storage Facility and to the east of the community of Holtwood. The route curves northeast into a mix of farmland and woodland with some homes near the community of Bethesda. PA 372 crosses Muddy Run into Drumore Township and continues through rural areas. The route reaches the community of Buck, where it comes to an intersection with PA 272.