The state highway heads northeast as Perryman Road, a two-lane undivided road that closely parallels Amtrak's Northeast Corridor railroad line, which also serves MARC's Penn Line.

MD 159 serves the Perryman Peninsula, an area of land between the Bush River estuary and Aberdeen Proving Ground.

A small portion of this area is on the south side of the railroad and is accessed via Chelsea Road, at which northbound MD 159 has a stop sign in the village of Perryman, where the highway veers away from the Amtrak line and passes St. George's Parish Vestry House.

North of Perryman, the state highway passes several distribution centers before reaching Old Philadelphia Road at a roundabout, onto which MD 159 turns west.

The state highway crosses over Cranberry Run and passes south of the Griffith House and north of a trailer park before reaching its northern terminus at an oblique intersection with US 40 (Philadelphia Boulevard) just south of the city limits of Aberdeen.