The Depression caused Hubert H. Humphrey to change his college plans and obtain a degree in pharmacy. He worked as a pharmacist for a few years before returning to the University of Minnesota for a political science degree. Following a stint as a college instructor, he headed the Minnesota branch of the Works Progress Administration. In 1943, as assistant regional director of the War Manpower Commission, he unsuccessfully ran for mayor of Minneapolis. He was successful in 1945.

Humphrey was heavily involved in founding the Americans for Democratic Action, a national, liberal, anti-Communist organization. In 1948, he became the first Minnesota Democrat elected to the U.S. Senate. He was re-elected in 1954 and 1960. He was vice president under President Lyndon B. Johnson. Humphrey lost his bid for the presidency in 1968.