PA 272 crosses the Octoraro Creek into Little Britain Township in Lancaster County and becomes Nottingham Road, curving northwest into agricultural areas with some trees and homes. The road reaches the community of Oak Hill and turns west, passing through more rural land. The route passes near residential development in the community of Little Britain before it continues through farmland and passes through Oakryn. PA 272 enters Fulton Township and runs through agricultural areas with occasional homes, reaching an intersection with US 222 in the community of Wakefield. At this point, the route turns north for a concurrency with US 222 along Robert Fulton Highway, running through a mix of farms and homes. PA 272 splits from US 222 in the community of Penn Hill by heading northwest along Lancaster Pike. The road heads through agricultural areas with some trees and homes, curving north and leaving Fulton Township, where it becomes the border between Drumore Township to the west and East Drumore Township to the east. The route continues through rural areas and turns northwest, passing through the communities of Hensell and Drumore Center. PA 272 curves north and runs through more farmland with some residential and commercial development before coming to an intersection with PA 372 in the community of Buck. At this intersection, PA 272 crosses westbound PA 372 while eastbound PA 372 turns north for a short concurrency with northbound PA 272 before it splits to the east.