Kefauver was born in Madisonville, Tennessee and attended the University of Tennessee and Yale University. He was a member of the United States House of Representatives from 1939 to 1949. He served in the United States Senate from 1949 to his death in 1963. He led a U.S. Senate committee investigating organized crime in 1950, that brought him national attention. He was the Democratic Party Vice Presidental nominee in 1956.

Although a Southerner, Kefauver was hated by his fellow Southerners for his liberal position on civil rights and his independence (the Southern Senators usually voted in a block).