Marca-Relli is credited with raising collage to the scale and complexity of monumental painting. He was the son of a journalist and he and his family traveled abroad often; he had his first art lessons as a child in Italy. From 1935-38, Marca-Relli worked for the WPA, through which he met de Kooning and Franz Kline, and after World War II moved to New York to study at Cooper Union. For the most part he was a self-taught artist, drawing insight from frequent trips to Italy and looking to artists such as de Chirico, Henri Rousseau and the Abstract Expressionists. Marca-Relli’s approach to collage was unique. He began by sketching forms onto a bare canvas, then arranging them on a new canvas, re-arranging shapes to gain his desired effect. His goal coincided with that of the Abstract Expressionists: to bring accident and gesture to the medium of collage. In the 1960s, he began adding new materials—vinyls, plastics, aluminums, and paper—to his large-scale works.
Marca-Relli was included in the 9th Street Show and all of the Stable Gallery Annuals. He joined Koontz Gallery in 1959 and maintained an active teaching career, which included positions at Yale University and the University of California, Berkeley. In 1967, Marca-Relli had a retrospective exhibition at the Whitney Museum of American Art and has been included in exhibitions at the Museum of Modern Art, the Smithsonian Institution, and the Art Institute of Chicago.