Milton Resnick was born in Russia, and arrived in New York City in 1922 at age five. He settled in Brooklyn with his family and attended public school where a teacher re-named him from his birth name of Rachmiel and nickname of Milya to Milton. At age 14, he enrolled in the commercial art program at the Pratt Institute Evening School of Art in Brooklyn, but a teacher there suggested he switch to fine arts, so the next year he enrolled in the American Artists' School in New York. Ad Reinhardt, future Abstract Expressionist, was a classmate, and the two shared a budding interest in abstraction.
During the Depression Resnick was in the Easel and Mural Division of the WPA of the Works Progress Administration. By 1938, he had his own studio on West 21st Street, close to that of Willem de Kooning, with whom he formed a close friendship in the 1960s. Resnick's art career was interrupted by World War II, and he served five years in the Army, stationed in Iceland and Europe. After the War he lived for three years in Paris, where among others, he associated with modernist sculptors Alberto Giacometti and Constantin Brancusi.
In 1948, Milton Resnick returned to New York, and used his G.I. benefits to enroll in abstract expressionist painter Hans Hofmann's school. He also took a studio on East 8th Street, near Jackson Pollock, de Kooning, and Franz Kline, and in September met artist Pat Passlof, whom he married in 1961.
During the 1950s and 1960s, Resnick earned respect for his Abstract Expressionist paintings and also was unique for being one of the few New York artists to have a large working space for large-scale canvases. In 1976, he purchased the space that served him to the end of his active career, an abandoned synagogue on Eldridge Street on New York's lower east side. It was near his wife's studio, which was another abandoned synagogue and purchased by the couple in 1963.