The roadway is named for Francis Lewis, a Queens resident who was a signer of the United States Declaration of Independence.

[2] Francis Lewis Boulevard begins at an intersection with 148th Avenue and Hook Creek Boulevard in Rosedale, Queens, continues due northwest and encounters its first major intersection (with NY 27 (South Conduit Avenue and Sunrise Highway)) approximately 0.8 miles (1.3 km) later, where it also crosses under the Long Island Rail Road's Montauk Branch.

[2] After 223rd Street, Francis Lewis Boulevard leaves 121st Avenue and resumes roughly the same northwestern alignment that it had before the Laurelton Parkway.

Neighborhoods traversed north of Springfield Boulevard are Cambria Heights, Hollis and Queens Village the western edge of Cunningham Park in Fresh Meadows, Auburndale, Bayside, and Whitestone, passing under the LIRR Main Line at the boundary of Hollis and Queens Village, NY 25 (Hillside Avenue), the Grand Central Parkway and the Horace Harding Expressway at the south and north ends of Cunningham Park, respectively, and NY 25A (Northern Boulevard) in Bayside.

[2][4][3] The Cunningham Park stretch of Francis Lewis Boulevard is notorious for drag racing, which has resulted in several fatalities to drivers and pedestrians over the years.

[9][10][11][12] The street was renamed after Francis Lewis, a signer of the Declaration of Independence who owned a home in Whitestone, to avoid confusion with the Cross Island Parkway.

These roads appeared on late 18th Century maps created by British general Sir Henry Clinton.

[26] On November 11, 1938, construction began on an upgrade to the north end of the boulevard, in order to serve as a link between the Bronx–Whitestone Bridge and the 1939 New York World's Fair.

[32] The road was completed in June 1943, but did not open due to restrictions by the New York City Police Department, which required lights to be installed along the route.

[32] The link provided a direct route from Southeast Queens to the Whitestone Bridge for trucks and other commercial traffic, which could not use the Cross Island Parkway.

Every year the two schools play a football game in the beginning of the season called the "Battle of the Boulevard", in reference to the shared stretch of road.