Main Street runs relatively north to south with two to three lanes in either direction, and serves as the major road for Flushing, Queens.

[4][5][6][7] The stretch of Main Street in Kew Gardens Hills south of the Long Island Expressway is home to a large Jewish community, including many Orthodox, Ashkenazi, and Bukharan Jews.

[2][8][9] At the south end of Kew Gardens Hills near Jamaica, Main Street intersects with Union Turnpike and the Grand Central Parkway service road.

Westbound Union Turnpike feeds into the Kew Gardens Interchange, connecting to the Grand Central, the Van Wyck Expressway, the Jackie Robinson Parkway, and Queens Boulevard.

[4][5][6][7] Near its southern end, two entrance ramps branch off from the center of Main Street, feeding into the southbound Van Wyck.

The two one-way spurs of Main Street run for three more blocks before ending in Briarwood, at adjacent intersections with Queens Boulevard.

The route, which ran between Kew Gardens – Union Turnpike station and Queens College, was eliminated in 2010 due to budget cuts within the MTA.

[18][19][20] The X51 express bus served a portion of the street between Elder Avenue near Kissena Park and Horace Harding Expressway, before being discontinued in the 2010 cuts due to low ridership.

[22] In October 2016, the New York City Department of Transportation announced that southbound traffic on Main Street between 37th Avenue and 40th Road would be converted to a busway restricted to buses and local delivery vehicles.

[29] In June 2020, mayor Bill de Blasio announced that the city would test out a northbound busway on Main Street in Downtown Flushing.

[30][31] Almost all Main Street business owners expressed opposition to the busway in a survey,[32] leading a New York Supreme Court judge to place an injunction in November 2020.

[5][7] The Downtown Flushing section of the route contains its busiest transit hub, revolving around the Flushing–Main Street terminal for the New York City Subway's 7 and <7>​ trains at Roosevelt Avenue.