The southern portion of the route from the Washington, D.C., border to Germantown is a suburban four- to six-lane divided highway lined with many businesses.

North of Germantown, the route is predominantly a two-lane rural road until it reaches Frederick, where it passes through commercial areas in the southern part of the city.

The same year, the portion of MD 355 north of I-70 was transferred to the city of Frederick and is no longer considered part of the route.

MD 355 is a part of the main National Highway System from the District of Columbia line to I-495, in Bethesda.

North of Friendship Heights, the route continues into the wooded residential area of Somerset, before passing the Chevy Chase Country Club on the east side of the road, and the residential areas of the town of Chevy Chase, and its associated villages, to the west.

[1] Past this intersection, MD 355 enters downtown Bethesda, where it heads back into commercial areas with high-rise buildings.

It leaves the downtown area of Bethesda and becomes Rockville Pike at the intersection with Glenbrook Parkway / Woodmont Avenue.

[1][4] Past this interchange, the road skirts the edge of Rock Creek Park, coming to an intersection with Grosvenor Lane that features a northbound jughandle.

MD 355 continues into residential areas of North Bethesda, where the Red Line parallels the route to the east to the Grosvenor–Strathmore station before returning to running under the road.

Farther north, the route comes to the intersection with MD 547 (Strathmore Avenue) east of Georgetown Preparatory School.

MD 355 passes to the west of the Nuclear Regulatory Commission headquarters and heads past the North Bethesda station along the Red Line.

[4] MD 355 heads into more commercial areas and passes the Rockville Campus of Montgomery College before intersecting Gude Drive.

Past this intersection, MD 355 becomes Frederick Road and heads northwest into a mix of commercial and residential areas in Derwood, drawing further away from the railroad tracks.

[4] It heads into business areas again and passes northeast of Gaithersburg High School as it approaches downtown Gaithersburg, where the route has an interchange with MD 117 (Diamond Avenue) and passes over CSX's Metropolitan Subdivision before continuing northwest past more businesses.

MD 355 passes more strip malls past this intersection before crossing over Great Seneca Creek and leaving Gaithersburg.

[1][4] The route continues northwest into Germantown through residential areas before passing businesses again and intersecting Middlebrook Road.

[1][4] The route eventually draws farther east of I-270 and heads through residential neighborhoods and woodland before reaching Hyattstown.

[1][4] Past this intersection, the road continues into a more rural setting consisting of farmland, woods, and some residential areas and businesses.

[1][4] In a short distance, MD 355 heads from rural areas into a commercial district on the outskirts of Frederick.

[12] The state road was completed between Germantown and Clarksburg and through Urbana to a point southeast of the community by 1923.

[29] In 2006, the northern terminus of MD 355 at the interchange with US 15 in Frederick was truncated to a dead end a short distance south of that route.

[33][34] Its June 2016 NBI report noted that this bridge is possibly eligible to be listed on the National Register of Historic Places.

[35] This bridge's NBI report, from September 2016, determined that its deck was in poor condition, with advanced section loss or deterioration.

[35] The 2016 inspection reports for both bridges concluded that both of these MD 355 carriers' deck geometries were "[b]asically intolerable requiring high priority of replacement.

[7] The first portion of the road opened in late 2005 from MD 355 south to a roundabout at Sugarloaf Parkway.

[42] In 2014, all of MD 355C except for a 0.376-mile (0.605 km) portion between a point south of Urbana Church Road and Sprigg Street was turned over to county maintenance.