Conrad Marca-Relli was born in Boston, Massachusetts. When he was thirteen, Marca-Relli and his parents moved to New York. In 1930 he studied at the Cooper Union for a year. He later supported himself by working for the Works Progress Administration, first as a teacher and then with mural painting divisions of the Federal Art Project during this period he won the Logan Medal of the arts. Conrad Marca-Relli served in the US Army military service during World War II (1941-1945).

After the war Marca-Relli joined the "Downtown Group" which represented group of artists who found studios in lower Manhattan in the area bounded by 8th and 12th street between First and Sixth Avenues during the late 1940s and early 1950s. During the late 1940s and early 1950s, he was actively involved in the avant-garde art world in Greenwich Village. These artists were called the "Downtown Group" as opposed to the "Uptown Group" established during the war at The Art of This Century Gallery.

In 1949 Conrad Marca-Relli was among the founders of the "Artists' Club" located at 39 East 8th Street.

He was chosen by his fellow artists to show in the Ninth Street Show held on May 21-June 10, 1951. The show was located at 60 East 9th Street on the first floor and the basement of a building which was about to be demolished.

"The artists celebrated not only the appearance of the dealers, collectors and museum people on the 9th Street, and the consequent exposure of their work but they celebrated the creation and the strength of a living community of significant dimensions."

Conrad Marca-Relli was among the 24 out of a total 256 New York School artists included in the Ninth Street Show and in all the following New York Painting and Sculpture Annuals from 1953 to 1957. These Annuals were important because the participants were chosen by the artists themselves.

Marca-Relli's early cityscapes, still lifes, circus themes and architectural motifs are reminiscent of Italian surrealist painter Giorgio de Chirico. The subdued palette and architectural starkness of these paintings create a sense of loneliness and emptiness typical of the surrealists.

Throughout his career Marca-Relli created monumental-scale collages. He combined oil painting and collage, employing intense colors, broken surfaces and expressionistic spattering. He also experimented with metal and vinyl materials. Over the years the collages developed an abstract simplicity, evidenced by black or somber colors and rectangular shapes isolated against a neutral backdrop.

Marca-Relli taught at Yale University from 1954 to 1955 and from 1959 to 1960, and at the University of California at Berkeley. His first one-man show was in New York City in 1948, and in 1967 the Whitney Museum of American Art gave him a retrospective show.

In 1953, he bought a house near Jackson Pollock’s home in Springs, East Hampton. As his career progressed, he increasingly distanced himself from the New York School.

He lived and worked in many countries around the world. In his final years, he lived in Parma, Italy with his wife, Anita Gibson, whom he married in 1951.

Conrad Marca-Relli died on August 29, 2000 in Parma.