In the 1930s he served on aviation bases in Hawaii, Texas, and Louisiana and studied at various army schools.
From August 1940, Twining held assorted staff positions in Washington, D.C., transferring as a brigadier general to the South Pacific in July 1942 to become chief of staff of army ground and air forces. Promoted to major general in 1943, he commanded the new Thirteenth Air Force in the Solomon Islands campaign and, in 1944 and 1945, the Fifteenth Air Force, based in southern Italy, that mounted numerous raids against German and Balkan targets, especially oil refineries, and provided air support for ground campaigns in Italy and southern France. Promoted to temporary lieutenant general, at the end of the war Twining commanded the Twentieth Air Force in the final bombing of Japan.
After holding postwar commands in Ohio and Alaska, Twining was promoted to full general and became U.S. Air Force vice chief of staff in 1950, later succeeding Hoyt S. Vandenberg as chief of staff. Under Twining, the Strategic Air Command (SAC) expanded, acquiring B-52 and XB-70 bombers to become the keystone of the massive retaliation nuclear strategy favored by President Dwight D. Eisenhower. Twining also forcefully advocated developing assorted intercontinental ballistic missile (ICBM) programs, including Jupiter and Atlas missiles and Polaris submarine-launched weapons, as part of a full and coordinated American nuclear defense strategy.
A hard-liner, Twining opposed the decreases in conventional defense forces envisaged by Eisenhower's 1953 New Look defense strategy. In 1957, Twining's repeated assertions of a bomber gap between the United States and the Soviet Union persuaded Congress to increase air force appropriations by $1 billion. Like JCS Chairman Arthur W. Radford, whom he succeeded in 1957, Twining unsuccessfully advocated a nuclear strike against communist Viet Minh forces during the 1954 siege of Dien Bien Phu in Indochina and also supported an uncompromising American commitment to defend Taiwan. By the late 1950s, some critics questioned his reliance on nuclear weapons, preferring a more flexible response capacity.
Twining retired in 1960, subsequently supporting American involvement in Vietnam, advising Republican presidential candidate Barry Goldwater in the 1964 election, and in the book Neither Liberty nor Safety (1966) fiercely criticizing President Lyndon Johnson's reluctance to modernize American nuclear weaponry. In the 1970s he opposed the Strategic Arms Limitation (SALT) and Anti-Ballistic Missile (ABM) Treaties, arguing that they compromised American national security. Twining died at Lackland Air Force Base in San Antonio, Texas, on 29 March 1982.
Moody, Walton S. Building a Strategic Air Force. Washington, DC: Air Force Museums and History Program, 1996.; Mrozek, Donald J. "Nathan F. Twining: New Dimensions, a New Look." Pp. 257–280 in Makers of the United States Air Force. Edited by John L. Frisbee. Washington, DC: U.S. Government Printing Office, 1987.; Schnabel, James, et al. The History of the Joint Chiefs of Staff: The Joint Chiefs of Staff and National Policy. 7 vols. to date. Washington, DC: Historical Division, U.S. Joint Chiefs of Staff, 1986–2000.; Webb, Willard J. The Chairmen of the Joint Chiefs of Staff. Washington, DC: Historical Division, U.S. Joint Chiefs of Staff, 1989.