Known as Delancy Road, the state highway runs 1.01 miles (1.63 km) from U.S. Route 40 (US 40) north to MD 281 in Elkton close to the Delaware state line.

Delancy Road was brought into the state highway system as MD 781 in 1984.

MD 781 begins at an intersection with US 40 (Pulaski Highway) in the town of Elkton 0.23 miles (0.37 km) west of the U.S. Highway's crossing of the Delaware state line.

The highway heads north as a two-lane undivided road to the west of the state line and to the east of Grays Hill.

That terminus is at MD 281 (Red Hill Road) 0.34 miles (0.55 km) west of that highway's crossing of the state line.