During World War II, chemists focused on the actinide series, a group name for elements with atomic numbers between 89 and 104 in the periodic table. Glenn Seaborg, Edwin McMillan, and colleagues at the University of California at Berkeley had discovered the elements 93, neptunium; 94, plutonium; 95, americium; and 96, curium. At Clinton Laboratories in Oak Ridge, chemists investigated these elements and the lanthanide series (elements with atomic numbers between 57 and 71), long known as the rare earth elements.

The existence of one rare earth, element 61, was predicted by the 1930s, but it had never been produced and identified before Charles Coryell's chemistry group at Clinton Laboratories did so in 1944. Larry Glendenin and Jacob Marinsky, using ion-exchange chromatography applied by Waldo Cohn for separating fission products, separated element 61 from other rare earth elements produced by uranium fission in the Graphite Reactor.

Too busy with defense-related chemistry during the war, Glendenin and Marinsky did not claim their discovery until 1946 after Coryell had moved to the Massachusetts Institute of Technology. Having established their claim as the discoverers of element 61, they were accorded the privilege of naming it. After considering "clintonium" in tribute to the Laboratories, they instead chose the name "promethium," suggested by Coryell's wife, in recognition of Prometheus of Greek mythology, who stole fire from heaven for human benefit.