Benton was born in Minneapolis, Minnesota. He was educated at Shattuck Military Academy, Faribault, Minnesota, and Carleton College in Northfield, Minnesota until 1918, at which point he matriculated at Yale University, where he was admitted to the Zeta Psi fraternity.
He graduated in 1921 and began work for advertising agencies in New York City and Chicago until 1929, after which he co-founded Benton & Bowles with Chester Bowles in New York. He moved to Norwalk, Connecticut in 1932, and served as the part-time vice president of the University of Chicago from 1937 to 1945.
He was appointed Assistant Secretary of State and held the position from 31 August 1945 to 30 September 1947, during which time he was active in organizing the United Nations. He was appointed to the United States Senate on 17 December 1949, and subsequently elected on 7 November 1950 as a Democrat to fill the vacancy caused by the resignation of Raymond E. Baldwin to the term ending 3 January 1953.
He defeated Prescott Sheldon Bush, father of U.S. President George Herbert Walker Bush and grandfather of current U.S. President George W. Bush. In 1951 he introduced a resolution to expel Joseph McCarthy from the Senate. However, he lost in an election for the full term in 1952. He was appointed United States Ambassador to UNESCO in Paris and served from 1963 to 1968.
For much of his life, from 1943 to his death, he was chairman of the board and publisher of the Encyclopædia Britannica, was a member of and delegate to numerous United Nations and international conferences and commissions, and trustee of several schools and colleges.
Benton established the Benton Foundation.