U.S. Route 240

US 240 began at the intersection of Pennsylvania Avenue and 14th Street near the White House in Washington. US 1 followed 14th Street through the intersection. Pennsylvania Avenue east of US 1 was part of District of Columbia Routes 4 and 5, which ran concurrently along Pennsylvania Avenue southeast around the Capitol and across the Anacostia River, east of which they diverged toward the D.C. ends of MD 4 and MD 5, respectively. US 240 headed west on Pennsylvania Avenue to 15th Street, then entered the White House grounds, which are today known as President's Park and features streets closed to the public. The U.S. Highway headed straight west for a block, then curved around the south side of the South Lawn (White House) to E Street, then followed E Street west to 17th Street. US 240 followed 17th Street north to Farragut Square, where the highway intersected K Street, which carried US 50.

US 240 continued north along Connecticut Avenue to Dupont Circle, which did not yet have an underpass for Connecticut Avenue. At the circle, the U.S. Highway met US 29, which used New Hampshire Avenue on both sides of the circle, and US 240 Alternate, which headed north on Connecticut Avenue. US 240 continued northwest on Massachusetts Avenue. The highway passed through Sheridan Circle, crossed Rock Creek on what is now named the Charles C. Glover Memorial Bridge, and passed along part of Observatory Circle on the edge of the circular U.S. Naval Observatory grounds. US 240 followed Massachusetts Avenue to its intersection with Wisconsin Avenue next to Washington National Cathedral. There, the U.S. Highway turned north and followed Wisconsin Avenue through Tenleytown to the District of Columbia boundary at Western Avenue in Friendship Heights.

US 240 followed a divided highway north to its intersection with MD 191, which as today headed west as Bradley Boulevard, a divided highway, and east as Bradley Lane. The U.S. highway became undivided and intersected MD 82 (Leland Street) and crossed over the Georgetown Branch of the Baltimore & Ohio Railroad before meeting the southern and western ends of MD 187 (Old Georgetown Road) and MD 410 (East–West Highway), respectively, in the center of Bethesda. This intersection also served as the northern end of US 240 Alternate, which headed east along MD 410 to Connecticut Avenue, which was then MD 193 and is now MD 185. North of Bethesda, US 240 met the western end of MD 702 (Jones Bridge Road) just south of the National Naval Medical Center. The highway descended into the valley of Rock Creek then left the valley and met the western end of MD 547 (Strathmore Avenue).

US 240 intersected Montrose Road and then the northern end of MD 187 (Old Georgetown Road) at the village of Montrose. The highway began to parallel the Baltimore & Ohio Railroad (now CSX's Metropolitan Subdivision) as it approached the town of Rockville. US 240 entered the county seat at Dodge Street and had an acute intersection with MD 28 (Viers Mill Road). The two highways ran concurrently northwest along a street that no longer exists to Montgomery Avenue, then west on Montgomery Avenue to Washington Street. There, MD 28 continued west on Montgomery Avenue and US 240 continued out of town on Washington Street. The U.S. Highway paralleled the railroad to Derwood, where the highway intersected MD 688 (Redland Road) just north of Indianola Drive. US 240 intersected Shady Grove Road and entered the town of Gaithersburg at Summit Avenue. The highway crossed over the Baltimore & Ohio Railroad between a pair of oblique intersections with MD 124 (West and East Diamond Avenue), which ran concurrently with US 240 across the railroad.

US 240 continued north from Gaithersburg across Great Seneca Creek to the hamlets of Middlebrook and Neelsville. In the latter location, the highway met the northern end of MD 118 (Germantown Road) at what is now Boland Farm Road and the southern end of MD 27 (Ridge Road) at what is presently Henderson Corner Road. US 240 crossed Little Seneca Creek and had a pair of staggered intersections with MD 121 (Clarksburg Road); the latter highway followed what are now Spire Street and Redgrave Place north and south, respectively. The U.S. Highway crossed Little Bennett Creek just south of the village of Hyattstown, where the highway intersected Old Hundred Road; MD 109 did not yet extend to Hyattstown. Just north of Hyattstown, US 240 crossed the Montgomery–Frederick county line and met the southern end of MD 75 (Green Valley Road).

US 240 crossed Bennett Creek as it approached Urbana, through which the highway ran concurrently with MD 80 (Fingerboard Road). The U.S. Highway descended into the valley of the Monocacy River, which the highway crossed just south of its bridge across the Old Main Line of the Baltimore & Ohio Railroad at Frederick Junction. South of the city limits of Frederick, US 240 had an oblique intersection with US 15 (Buckeystown Pike) just south of the modern intersection of MD 355 and MD 85. US 15 and US 240 entered Frederick together along Market Street. The U.S. Highways crossed Carroll Creek before US 240 ended at US 40 (Patrick Street) in the center of downtown Frederick. US 15 continued north along Market Street toward Gettysburg.