Valued at $22m-28m, the work was created shortly after Hopper's fall 1933 retrospective at the Museum of Modern Art in New York - a pivotal moment in his career.
Hopper's studio was situated in New York City, and he would occasionally travel across the Hudson River to seek out new subject matter.
Weehawken, a sleepy suburb in New Jersey, became the subject of eight preparatory sketches for the present work, each of which is accompanied by extensive notes about the area.
Attempting to capture the melancholy and loneliness of Depression-era America, the work is painted from the perspective of one looking through a car window on a deserted intersection.
The current auction record for Hopper's work is held by Hotel Window, which sold for $26.8m in 2006.
Selling with a $1.8m-2.4m estimate is another of the auction's highlights, In the Key of Blue by Charles Demuth. Painted circa 1919-1920, the work is described by Christie's as "a tour-de-force that demonstrates Charles Demuth at the height of his abilities."
Executed in tempera, the work is part of a series of works that are much larger in scale than Demuth's previous watercolours. According to Christie's, it is a direct precursor to masterworks such as My Egypt (1927).
Paul Fraser Collectibles' free weekly newsletter brings you all the latest news direct to your inbox.