MD 180 begins at a partial interchange with US 340 (Jefferson National Pike) just east of the southern end of South Mountain at the Potomac River. There is no access from westbound MD 180 to eastbound US 340 or from westbound US 340 to eastbound MD 180. The state highway heads east as two-lane undivided Jefferson Pike, which parallels the Chesapeake and Ohio Canal and CSX's Metropolitan Subdivision to the village of Knoxville. MD 180 makes a sharp curve to the northeast in which the highway intersects MD 478 (Knoxville Road), which parallels the railroad, canal, and river east to Brunswick.