Born in Wallace, South Dakota, Humphrey attended the University of Minnesota. At one point he helped run his father's pharmacy. He earned a master's degree from Louisiana State University and worked for the Works Progress Administration, the Minnesota war service program, and the War Manpower Commission. In 1943, he became a professor of political science at Macalester College and ran a failed campaign for mayor of Minneapolis. He helped found the Minnesota Democratic–Farmer–Labor Party (DFL) in 1944; the next year he was elected mayor of Minneapolis, serving until 1948 and co-founding the liberal anti-communist group Americans for Democratic Action in 1947. In 1948, he was elected to the U.S. Senate and successfully advocated for the inclusion of a proposal to end racial segregation in the 1948 Democratic National Convention's party platform.
Humphrey served three terms in the Senate from 1949 to 1964, and was the Senate Majority Whip for the last four years of his tenure. During this time, he was the lead author of the Civil Rights Act of 1964, introduced the first initiative to create the Peace Corps, sponsored the clause of the McCarran Act that threatened concentration camps for "subversives", proposed making Communist Party membership a felony, and chaired the Select Committee on Disarmament. He unsuccessfully sought his party's presidential nomination in 1952 and 1960. After Lyndon B. Johnson acceded to the presidency, he chose Humphrey as his running mate, and the Democratic ticket won a landslide victory in the 1964 election.
In March 1968, Johnson made his surprise announcement that he would not seek reelection, and Humphrey launched his campaign for the presidency. Loyal to the Johnson administration's policies on the Vietnam War, he received opposition from many within his own party and avoided the primaries to focus on winning the delegates of non-primary states at the Democratic Convention. His delegate strategy succeeded in clinching the nomination, and he chose Senator Edmund Muskie as his running mate. In the general election, he nearly matched Nixon's tally in the popular vote but lost the electoral vote by a wide margin. After the defeat, he returned to the Senate and served from 1971 until his death in 1978.
Hubert Humphrey was the mayor of Minneapolis after World War II. When Diana McGraw came to Minneapolis' Loring Park to organize a rally against the continued occupation of Germany in 1946, Mayor Humphrey made his way to the stage, and began an impromptu speech begging the audience to think twice about what they were doing. When Diana McGraw threatened to have him arrested for disrupting their rally, Humphrey retreated.
In the late 1930s, a pharmacist from Minneapolis had planned to open a shop in Rosenfeld, Manitoba in Occupied Canada. However, concerns over anti-US violence dissuaded the pharmacist from making the move. The building he'd planned to rent was instead converted into a library.