The highway serves as one of the main streets of Annapolis, including the state capital's historic core, and is the primary vehicular access to the U.S.

The MD 2 portion of the highway was constructed in the early to mid-1910s except for the first modern bridge across the Severn River, which was completed in the mid-1920s.

US 1 Alternate heads southwest as Bladensburg Road into Colmar Manor and north as Baltimore Avenue toward Hyattsville.

Adjacent to the center intersection of the junction is the Peace Cross, a memorial to World War I soldiers.

East of the railroad underpass, the highway has a partial cloverleaf interchange with MD 201 (Kenilworth Avenue).

MD 450 continues as a six-lane divided highway and leaves the town of Bladensburg at its partial cloverleaf interchange with the Baltimore–Washington Parkway.

The highway passes between the town of Landover Hills and the unincorporated area of Woodlawn and intersects MD 410 (Veterans Parkway).

[1][3] MD 450 meets the northern end of Whitfield Chapel Road just east of the railroad bridge.

It drops to two lanes as it leaves the city of Bowie east of Race Track Road and west of historic Sacred Heart Church.

MD 450 has an oblique four-ramp partial cloverleaf with US 50/US 301 (John Hanson Highway), which run concurrently with unsigned I-595.

The highway reduces to two lanes east of Chinquapin Round Road and meets the southern end of MD 435 (Taylor Avenue) and the northern end of MD 387 (Spa Road) at the Westgate Circle roundabout next to Annapolis National Cemetery.

The highway passes along the edge of St. John's College to King George Street, onto which the route turns northwest.

Naval Academy reservation to College Creek, where the highway becomes state maintained again and leaves the city of Annapolis.

After a diversion through the interchange, Governor Ritchie Highway continues north toward Baltimore carrying MD 2.

The highway through the Naval Academy reservation from College Creek to the south side of the Severn River was built as a 16-foot-wide (4.9 m) macadam road in 1916.

[8][9] The western portion was extended east through Lanham to the Washington, Baltimore and Annapolis Electric Railway (WB&A) at Buena Vista near what is now MD 704 by 1923.

[6][10] Other major structures along the route included a steel and concrete girder bridge across the Popes Creek Subdivision near Bowie in 1926 and reinforced concrete girder bridges across the North River and the South River completed in 1925.

The portion of MD 2 through the Naval Academy reservation was widened to 22 feet (6.7 m) with a pair of 3-foot-wide (0.91 m) concrete shoulders in 1927.

US 50's bridges across the Pennsylvania Railroad (now Amtrak's Northeast Corridor) at Lanham and the WB&A at Buena Vista were started in 1930.

[15] In addition, the present alignment of MD 450 from the Severn River north to Arnold was completed as the southernmost portion of Governor Ritchie Highway.

[28] In Prince George's County, the extension of John Hanson Highway west toward Washington began in 1953.

[25] US 50 remained signed along Defense Highway in Prince George's County; instead, the new freeway and MD 704 southwest into Washington were designated Temporary US 50 by 1958.

That same year, MD 450 was extended west along US 50's old route to its present western terminus at US 1 Alternate in Bladensburg.

[22][30] Starting in 1956, the Peace Cross intersection was raised to a higher elevation above the Anacostia River and reconstructed to reduce the risk of flooding.

[35] In 1985, the road was expanded to a divided highway on either side of its modern intersection with MD 193, which had been relocated onto Glenn Dale Boulevard that year.