Upon crossing the Nanticoke River, US 50 heads into Wicomico County and runs through marshland before heading into forests and turning to the south. The route intersects Old Bradley Road (MD 731C), which provides access to an eastbound inspection station for buses and trucks. The road has an intersection with Marsh Road (MD 731A), a one-way road coming from the inspection station, and curves to the southeast. US 50 continues through a mix of farmland and woodland with some residential and commercial development, turning to the east as it passes north of a roadside picnic area. The route heads into Mardela Springs and passes to the north of the residential areas of the town. US 50 reaches an intersection with the southern terminus of MD 313, which heads east a short distance to the western terminus of MD 54 before turning north. From here, the road leaves Mardela Springs and runs through more rural land with some development. The route passes through open agricultural areas with some woodland and homes, curving to the southeast. US 50 intersects the northern terminus of MD 347, which heads southwest into Hebron. A short distance later, the route has a junction with the eastern terminus of MD 670, which leads west into Hebron. From here, the road runs through more rural areas with some residences and commercial establishments.