The son of the railroad magnate E.H. Harriman, W. Averell Harriman began his employment with the Union Pacific Railroad Company in 1915; he served as chairman of the board (1932–46). During the Franklin D. Roosevelt administration he was an officer of the National Recovery Administration and during 1940–41 served with the National Defense Advisory Commission and its successor agency, the Office of Production Management. In 1941 President Roosevelt (Roosevelt, Franklin D.) sent him to Britain and the Soviet Union to expedite U.S. lend-lease aid. He then served as U.S. ambassador to the Soviet Union (1943–46), ambassador to Great Britain (April to October 1946), and secretary of commerce (1947–48).

From 1948 to 1950 he was special U.S. representative in Europe to supervise administration of the European Recovery program; in 1950 he was named special assistant to the president and in 1951 director of the Mutual Security Agency. He was twice unsuccessful in his attempt to win the Democratic nomination for the presidency (1952 and 1956). Governor of New York from 1954 to 1958, Harriman lost the position to Nelson A. Rockefeller. He served as Pres. John F. Kennedy's (Kennedy, John F.) assistant secretary of state for Far Eastern affairs from 1961 to 1963. During that period he advocated U.S. support of a neutral government in Laos and helped to negotiate the Nuclear Test-Ban Treaty. Under Pres. Lyndon B. Johnson (Johnson, Lyndon B.) Harriman served as ambassador-at-large and headed the U.S. delegation to the Paris peace talks between the United States and North Vietnam (1968–69). He retired in 1969 (though he remained active in foreign affairs in an unofficial capacity) and was replaced by Henry Cabot Lodge.

Harriman's reflections on his relations with the Soviet Union, America and Russia in a Changing World, appeared in 1971 and his Special Envoy to Churchill and Stalin, 1941–1946 (with Elie Abel) in 1975.