Muskie was born in Rumford, Maine and graduated from Bates College, Lewiston, Maine, in 1936, and Cornell University Law School, in 1939. He served in the United States Navy during World War II.
He served in the Maine state house of representatives before serving as Governor of Maine 1955-1959. He was elected to the U.S. Senate in 1958 and served there from January 3, 1959, until his resignation May 7, 1980. He was the Democratic Party's Vice President nominee in 1968, and ran for President in 1972, though he withdrew after losing the Democratic nomination to George McGovern. He served as United States Secretary of State from 1980 to 1981 during the Jimmy Carter administration, following the resignation of Cyrus Vance. Muskie was succeeded in the senate by George Mitchell.