The state highway runs 37.38 miles (60.16 km) from U.S. Route 15 (US 15) in Point of Rocks east to MD 182 in Norwood.

The state highway heads east as two-lane undivided Clay Street, which parallels CSX's Metropolitan Subdivision rail line and the linear Chesapeake and Ohio Canal National Historical Park through town.

The state highway parallels and then crosses at-grade to the south side of the Old Main Line Subdivision at the east end of town.

The highway passes through the hamlet of Tuscarora before reaching a three-way intersection with MD 85, which heads north as Buckeystown Pike.

[1][5] MD 28 heads southeast and crosses the Monocacy River at Furnace Ford shortly before entering Montgomery County.

Ephraim Road, MD 28 turns south and passes through a narrow underpass of the Metropolitan Subdivision rail line.

MD 28 crosses the Little Monocacy River before the intersection with Martinsburg Road, which heads southwest toward the Dickerson Generating Station and White's Ferry.

The highway crosses Muddy Branch parallel to a pair of spurs on the south designated MD 899 (American Way).

[1][5] MD 28 continues through the West Montgomery Avenue Historic District as a two-lane road with center turn lane.

At Great Falls Road, near the Beall-Dawson House, the state highway veers southeast onto four-lane Jefferson Street through the Montgomery County Courthouse Historic District along the southern edge of downtown Rockville.

The highway heads southeast of a park and ride lot that is accessed from MD 928 before it reduces to a two-lane road and runs along the northern edge of Leisure World.

The highway's original western terminus was at Tuscarora, from which US 15 headed west toward Point of Rocks and north toward Frederick.

[13][6] In 1981, MD 28 was made a divided highway between downtown Rockville and Baltimore Avenue west of Rock Creek.

[15] In the mid 1990s, Key West Avenue in the western part of Rockville was completed and expanded to a six-lane divided highway.