MD 180 was assigned to the highway bypassed by the US 340 freeway between Sandy Hook in far southern Washington County and Jefferson in the mid-1960s.

The state highway was extended east to Frederick and south along Ballenger Creek Pike (former MD 351) after the US 340 freeway was completed in the late 1960s.

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.

The state highway heads east as two-lane undivided Jefferson Pike, which parallels the Chesapeake and Ohio Canal and CSX's Metropolitan Subdivision railroad line to the village of Knoxville.

[1][2] MD 180 heads northeast and temporarily gains an eastbound climbing lane as it leaves the narrow Potomac River valley.

The state highway passes through farmland and meets MD 17 (Burkittsville Road) at a roundabout west of Rosemont.

MD 180 descends into the narrow valley of Catoctin Creek; the westbound direction has a short climbing lane.

[1][2] MD 180 parallels US 340 through a wide gap in Catoctin Mountain and continues northeast to the hamlet of Feagaville, where the highway intersects Mt.

MD 180 crosses over I-70 (Eisenhower Memorial Highway) and intersects Butterfly Lane near Saint John's Catholic Prep before beginning a sweeping curve to the south.

That same year, Keep Tryst Road was removed from the state highway system, leaving behind the stub that is current MD 180A.