After graduating from the University of California at Berkeley in 1937, McNamara earned a graduate degree at the Harvard Business School (1939) and later joined the Harvard faculty. Disqualified by poor vision from active duty during World War II, he developed logistical systems for bomber raids and statistical systems for monitoring troops and supplies.

After the war, McNamara was one of the “Whiz Kids” hired to revitalize the Ford Motor Company. His plans, including the institution of strict cost-accounting methods and the development of both compact and luxury models, met with success, and McNamara rose rapidly in the corporate ranks. In 1960 he became the first person outside the Ford family to assume presidency of the company.

After just one month as Ford's president, however, McNamara resigned to join the Kennedy (Kennedy, John F.) administration as secretary of defense. In his new post he successfully gained control of Pentagon operations and the military bureaucracy, encouraged the modernization of the armed forces, restructured budget procedures, and cut costs by refusing to spend money on what he believed were unnecessary or obsolete weapons systems. McNamara was also at the centre of a drive to alter U.S. military strategy from the “massive retaliation” of the Eisenhower years to a “flexible response,” emphasizing counterinsurgency techniques and second-strike nuclear-missile capability.

McNamara initially supported the deepening military involvement of the United States in Vietnam (Vietnam War). On visits to South Vietnam in 1962, 1964, and 1966, the secretary publicly expressed optimism that the National Liberation Front and its North Vietnamese allies would soon abandon their attempt to overthrow the U.S.-backed Saigon regime. He became the government's chief spokesman for the day-to-day operations of the war and acted as President Lyndon B. Johnson (Johnson, Lyndon B.)'s principal deputy in the war's prosecution.

As early as 1965, however, McNamara had begun to question the wisdom of U.S. military involvement in Vietnam, and by 1967 he was openly seeking a way to launch peace negotiations. He initiated a full-scale investigation of the American commitment to Vietnam (later published as The Pentagon Papers), came out in opposition to continued bombing of North Vietnam (for which he lost influence in the Johnson administration), and in February 1968 left the Pentagon to become president of the World Bank.

In his 13-year tenure as head of that institution, McNamara displayed what was generally regarded as great sensitivity to the needs of Third World nations. He retired from the World Bank in 1981 but remained active in many other organizations. He addressed issues such as world hunger, East-West relations, and other policy matters. His policy papers were published in two volumes, and his book Blundering into Disaster: Surviving the First Century in a Nuclear Age (1986) discusses nuclear war.

In 1995 McNamara published a memoir, In Retrospect: The Tragedy and Lessons of Vietnam, in which he describes the anticommunist political climate of the era, mistaken assumptions of foreign policy, and misjudgments on the part of the military that combined to create the Vietnam debacle. In the documentary film The Fog of War (2003), McNamara discusses his career in the Pentagon as well as U.S. failures in Vietnam.