Born in Nyack, New York, Hopper studied commercial art and painting in New York City. One of his teachers, artist Robert Henri, encouraged his students to use their art to "make a stir in the world." Henri, an influence on Hopper, motivated students to render realistic depictions of urban life. Henri's students, many of whom developed into important artists, became known as the Ashcan School of American art.

Upon completing his formal education, Hopper made three trips to Europe to study the emerging art scene there, but unlike many of his contemporaries who imitated the abstract cubist experiments, the idealism of the realist painters enamored Hopper. His early projects reflect the realist influence.

While he worked for several years as a commercial artist, Hopper continued painting. In 1925 he produced House by the Railroad, a classic work that marks his artistic maturity. The piece is the first of a series of stark urban and rural scenes that uses sharp lines and large shapes, played upon by unusual lighting to capture the lonely mood of his subjects. He derived his subject matter from the common features of American life - gas stations, motels, the railroad, or an empty street.

The best known of these paintings, Nighthawks (1942), shows the lonely customers frequenting a downtown all-night diner. The diner's harsh electric lights set it off from the gentle night outside. The diners, seated at stools around the counter, are similarly isolated from one another, reflecting on themselves.

Other examples include Chop Suey, Rooms for Tourists , and Office in a Small City.

Hopper's rural New England scenes, such as Gas (1940), are no less wistful. In terms of subject matter, he can be compared to his contemporary, Norman Rockwell, but while Rockwell exalted in the rich imagery of small-town America, Hopper depicts it in the same sense of forlorn solitude that permeates his portrayal of city life. Here too, Hopper's work exploits vast empty spaces, represented by a lonely gas station astride an empty country road and the sharp contrast between the natural light of the sky, moderated by the lush forest, and glaring artificial light coming from inside the gas station.

Hopper continued to paint in his old age, dividing his time between New York City and Truro, Massachusetts. He died in 1967, in his studio near Washington Square, in New York City. His wife, painter Josephine Nivison, who died 10 months later, bequeathed his work to the Whitney Museum of American Art. Other significant paintings by Hopper are at the Museum of Modern Art in New York and the Art Institute of Chicago.

In 2004, a large selection of Hopper's paintings toured through Europe, visiting Cologne, Germany and Tate Modern in London. The Tate exhibition became the second most popular in the gallery's history, with 420,000 visitors in the three months it was open. Also in 2004 British guitarist John Squire (formerly of The Stone Roses fame) released a concept album based on Hopper's work entitled Marshall's House. Each song on the album inspired by, and sharing its title with, a painting by Hopper.