Upon reaching Millersville, the route heads into developed areas and turns northeast, crossing PA 741.

PA 999 continues through rural areas and becomes Blue Rock Road before it runs through the communities of Central Manor and Windom.

Farther east, the road passes to the north of a residential neighborhood and crosses Little Conestoga Creek in a wooded area.

At the intersection with North George Street, which heads south to the Millersville University of Pennsylvania campus, the route turns northeast and becomes Manor Avenue.

PA 999 enters the city of Lancaster and becomes Manor Street, passing through urban areas of homes and businesses.