After service as a pilot in World War II, for which he was awarded the Distinguished Flying Cross, McGovern earned a Ph.D. in history at Northwestern University, Evanston, Ill., and later taught at Dakota Wesleyan University, Mitchell, S.D. He was active in Democratic politics, beginning in 1948, and served in the House of Representatives (1957–60). After losing an election for a Senate seat in South Dakota in 1960, he served for two years as the director of the Food for Peace Program under President John F. Kennedy. Stressing farm-support programs, McGovern won election to the U.S. Senate in 1962 and was reelected in 1968. By then he had emerged as one of the leading opponents to the United States' continued military involvement in Indochina.

As chairman of a Commission on Party Structure and Delegate Selection prior to the Democratic National Convention in 1972, McGovern helped enact party reforms that gave increased representation to minority groups at the convention. Supported by these groups, he won the presidential nomination but alienated many of the more traditional elements in the Democratic Party. McGovern was unable to unify the party sufficiently to offer an effective challenge to the incumbent Republican president, Richard M. Nixon (Nixon, Richard M.), who defeated him by an overwhelming margin.

McGovern was reelected to the Senate in 1974, but lost his seat in 1980 to a Republican opponent supported by right-wing groups. After lecturing as a visiting professor in foreign policy at several universities, including Northwestern University, McGovern declared himself a candidate for the 1984 Democratic presidential nomination, but decided to drop out of the race after a third-place finish in the Massachusetts primary—the only state that he had carried in the 1972 election. Although unsuccessful, his 1984 bid for the nomination did serve to reassert his status as a noted American spokesman for liberal causes.

McGovern's autobiography, entitled Grassroots, was published in 1978.