Dean Rusk combined academic work, wartime military service and diplomacy before becoming secretary of state. After teaching at Mills College, he served in the United States Army during the Second World War, including assignments concerned with operations in Asia. He entered the State Department after the war and rose through posts dealing with international organization and the Far East. During the Korean War he helped shape policy under Secretary of State Dean Acheson.

From 1952 to 1961 he headed the Rockefeller Foundation. John F. Kennedy then appointed him secretary of state, a position he held throughout both the Kennedy and Lyndon B. Johnson administrations. Rusk understood the office as one of advice and implementation under presidential direction. He favoured maintaining alliances, containing communist expansion and supporting newly independent states through diplomatic and economic assistance.

His tenure included the failed Bay of Pigs invasion, the Berlin confrontation, the Cuban Missile Crisis and negotiation of the Limited Nuclear Test Ban Treaty. He supported communication with the Soviet Union while remaining committed to the United States' security obligations.

Vietnam became the defining controversy of his career. Rusk supported the defence of South Vietnam and argued that retreat would weaken American commitments elsewhere. He remained a leading defender of Johnson's escalation despite mounting casualties, domestic opposition and doubts about the war's prospects. His loyalty made him a target for critics who regarded the policy as both ineffective and destructive. Leaving office in January 1969, he later taught international law at the University of Georgia and helped develop its international affairs programme. His memoir, As I Saw It, written with his son Richard, offered his account of the decisions and assumptions behind a long and disputed period of American diplomacy.