Known for most of its length as Oldtown Road, the state highway runs 25.53 miles (41.09 km) from an interchange with Interstate 68 (I-68) in Cumberland south to the West Virginia state line at the Potomac River, where the highway continues east as West Virginia Route 9 (WV 9) toward Paw Paw.

Around Cumberland, MD 51 is a major highway that provides a bypass of the South End neighborhood of that city and access to industrial areas along the North Branch Potomac River.

South of North Branch, MD 51 is a rural highway connecting small communities along the river in southeastern Allegany County, including Oldtown.

Just south of its terminus, the state highway intersects Winston Street and Queen City Drive and receives a ramp from eastbound I-68.

The state highway turns to a more eastward direction and gains a wide median with houses and businesses just before intersecting Virginia Avenue.

The state highway turns away from the North Branch Potomac River and passes through a hilly area south of Warrior Mountain before entering the valley of Mill Run.

Within Oldtown, the state highway intersects Opessa Street, which leads to a private, low-water toll bridge across the North Branch Potomac River to CR 1 (Green Spring Road) in Hampshire County, West Virginia.

[3] MD 51 separates from the C&O Canal again as it leaves Oldtown and enters the valley of Sawpit Run, which the road follows to its confluence with Town Creek.

[7] MD 51 was extended to Spring Gap between 1924 and 1926, including an underpass of the Western Maryland Railway at North Branch.

[11][12] In 1934, the highway was named for G. Clinton Uhl, a native of Mount Savage who was chairman of the Maryland State Roads Commission from 1929 until his death in 1934.