Wisconsin Avenue is a major thoroughfare in Washington, D.C., and its Maryland suburbs. It starts in Georgetown just north of the Potomac River, at an intersection with K Street under the Whitehurst Freeway. The section of Wisconsin Avenue in Georgetown was called High Street before the street names in Georgetown were changed in 1895 to conform to those of the L'Enfant plan for the federal city (although Georgetown predates the planned capital by half a century).

From Georgetown, Wisconsin Avenue runs north through Northwest D.C. passing through the neighborhoods of Tenleytown and Friendship Heights. While in Friendship Heights, Wisconsin Avenue intersects with Western Avenue (which forms much of the Northwest border of Washington, D.C.) and then crosses into Montgomery County, Maryland. In Maryland, it is officially known as Maryland Route 355. The segment of Wisconsin Avenue through Friendship Heights, Maryland, is nicknamed "Rodeo Drive East" because of its high-end shopping. Wisconsin Avenue then passes through Bethesda, where it is one of the main streets of the downtown area. Southbound traffic on Wisconsin Avenue can bypass downtown Bethesda by taking Woodmont Avenue.

Just north of downtown Bethesda, at the intersection with Glenbrook Parkway, its name changes to Rockville Pike. Rockville Pike runs along the National Institutes of Health, the United States National Library of Medicine, and the National Naval Medical Center and has an incomplete interchange with the Capital Beltway at exit 34. The Pike then runs through North Bethesda into Rockville, which is the county seat of Montgomery County. This part of Rockville Pike is home to many strip malls and is notorious for its congestion.

One aspect of Rockville Pike that confuses many motorists is the system of assigning building numbers. In unincorporated areas of the county, building numbers are assigned according to the addressing system in use in Montgomery County, a Cartesian coordinate plane with its origin at the United States Capitol. Within the city limits of Rockville, however, the origin of the numbering system is at the center of Rockville. Thus, someone driving north on the Pike sees building numbers above 12000 and rising, which suddenly give way to building numbers below 2000 and falling.

Near the center of Rockville, the name changes to Hungerford Drive for a short while. In the outskirts of Rockville, the name changes to Frederick Road. However, in the city of Gaithersburg, the road is known as South Frederick Avenue south of Diamond Avenue in downtown, and North Frederick Road north of Diamond Avenue. Upon leaving Gaithersburg city limits, the name returns to Frederick Road, which continues through the unincorporated communities of Germantown and Clarksburg, both rapidly developing suburbs. Upon entering Frederick County and the unincorporated community of Urbana, the road is known as Urbana Pike. It ends at U.S. Highway 15, just north of the city of Frederick, which is the county seat. In downtown Frederick, the route is known as Market Street.

From the Tenleytown-AU station north, Wisconsin Avenue/Rockville Pike/Route 355 runs approximately parallel to the Red Line of the Washington Metro. North of the Capital Beltway until Frederick (at the Interstate 70 junction), the highway runs parallel to Interstate 270, which handles express traffic through Montgomery and southern Frederick counties.

Wisconsin Avenue was once U.S. Highway 240. Outside of the Beltway, U.S. Highway 240 was relocated to what is today Interstate 270. Eventually, the entire route designation was decommissioned.

Wisconsin Avenue/Rockville Pike is part of the National Highway System as an arterial route from M Street to the Beltway and as an intermodal connector from the Beltway to the Grosvenor Metro station.

Streets in Washington, D.C. | Montgomery County, Maryland | Maryland state highways