The Rotterdam Academy of Fine Art accepted de Kooning as a student in 1916. In 1926 he stowed away on a British freighter, the SS Shelly, to Newport, Virginia. He then went by ship to Boston, and took a train from Boston to Rhode Island. From there, he took another ship to New Jersey.

De Kooning made his living for a time as a house painter. Later, he was a teacher at Black Mountain College with John Cage, Buckminster Fuller and Josef Albers.

In the post World War II era, de Kooning painted in the area of abstract expressionism, sometimes labeled an action painter. Others in this movement include Jackson Pollock, Mark Rothko and Clyfford Still. Later, de Kooning experimented with other art movements.

De Kooning's parents, Leendert de Kooning and Cornelia Nobel, were divorced when he was about five years old, and he was raised by his mother and a stepfather. In 1916 he was apprenticed to a firm of commercial artists and decorators, and, about the same time, he enrolled in night classes at the Rotterdam Academy of Fine Arts and Techniques, where he studied for eight years. In 1920 he went to work for the art director of a large department store.

In 1926 de Kooning entered the United States as a stowaway and eventually settled in Hoboken, New Jersey, where he supported himself as a house painter. In 1927 he moved to a studio in Manhattan and came under the influence of the artist, connoisseur, and art critic John D. Graham and the painter Arshile Gorky. Gorky became one of de Kooning's closest friends.

From about 1928 de Kooning began to paint still life and figure compositions reflecting schools of Paris and Mexican influences. By the early 1930s he was exploring abstraction, using biomorphic shapes and simple geometric compositions, an opposition of disparate formal elements that prevails in his work throughout his career. These early works have strong affinities with those of his friends Graham and Gorky and reflect the impact on these young artists of Pablo Picasso and the Surrealist Joan Miró, both of whom achieved powerfully expressive compositions through biomorphic forms.

In October 1935 de Kooning began to work on the WPA (Works Progress Administration) Federal Art Project. He was employed by this work-relief program until July 1937, when he resigned because of his alien status. This period of about two years provided the artist,who had been supporting himself during the early Depression by commercial jobs, with his first opportunity to devote full time to creative work. He worked on both the easel-painting and mural divisions of the project (the several murals he designed were never executed).

In 1938, probably under the influence of Gorky, de Kooning embarked on a series of male figures, including Two Men Standing, Man, and Seated Figure (Classic Male), while simultaneously embarking on a more purist series of lyrically colored abstractions, such as Pink Landscape and Elegy. As his work progressed, the heightened colors and elegant lines of the abstractions began to creep into the more figurative works, and the coincidence of figures and abstractions continued well into the 1940s. This period includes the representational but somewhat geometricized Woman and Standing Man, along with numerous untitled abstractions whose biomorphic forms increasingly suggest the presence of figures. By about 1945 the two tendencies seemed to fuse perfectly in Pink Angels. In 1946, too poor to buy artists' pigments, he turned to black and white household enamels to paint a series of large abstractions; of these works, Light in August (c. 1946) and Black Friday (1948) are essentially black with white elements, whereas Zurich (1947) and Mailbox (1947/48) are white with black. Developing out of these works in the period after his first show were complex, agitated abstractions such as Asheville (1948/49), Attic (1949), and Excavation (1950; Art Institute, Chicago), which reintroduced color and seem to sum up with taut decisiveness the problems of free-associative composition he had struggled with for many years.

In 1938 de Kooning met Elaine Marie Fried, later known as Elaine de Kooning, whom he married in 1943. She also became a significant artist. During the 1940s and thereafter he became increasingly identified with the Abstract Expressionist movement and was recognized as one of its leaders in the mid-1950s. He had his first one-man show, which consisted of his black-and-white enamel compositions, at the Charles Egan Gallery in New York in 1948 and taught at Black Mountain College in North Carolina in 1948 and at the Yale School of Art in 1950/51.