The first use of the term "weapon of mass destruction" on record is by Cosmo Gordon Lang, Archbishop of Canterbury, in 1937 in reference to the aerial bombardment of Guernica, Spain:

At that time, there were no nuclear weapons; biological weapons were already being researched by Japan (see Unit 731), and chemical weapons had seen wide use, most notably in World War I.

Following the atomic bombings of Hiroshima and Nagasaki, and progressing through the Cold War, the term came to refer more to non-conventional weapons. The application of the term to specifically nuclear and radiological weapons is traced by William Safire to the Russian phrase "Оружие массового поражения" - oruziye massovogo porazheniya.

He credits James Goodby (of the Brookings Institution) with tracing what he considers the earliest known English-language use soon after the nuclear bombing of Hiroshima and Nagasaki (although it is not quite verbatim): a communique from a November 15, 1945, meeting of Harry Truman, Clement Attlee and Mackenzie King (probably drafted by Vannevar Bush– or so Bush claimed in 1970) referred to "weapons adaptable to mass destruction".

That exact phrase, says Safire, was also used by Bernard Baruch in 1946 (in a speech at the United Nations probably written by Herbert Bayard Swope). The same phrase found its way into the UN resolution to create the Atomic Energy Commission (predecessor of the International Atomic Energy Agency (IAEA)), which used the wording "... atomic weapons and of all other weapons adaptable to mass destruction".

An exact use of this term was given in a lecture "Atomic Energy as an Atomic Problem" by J. Robert Oppenheimer. The lecture was delivered to the Foreign Service and the State Department, on September 17, 1947. The lecture is reprinted in The Open Mind (New York: Simon and Schuster, 1955).

"It is a very far reaching control which would eliminate the rivalry between nations in this field, which would prevent the surreptitious arming of one nation against another, which would provide some cushion of time before atomic attack, and presumably therefore before any attack with weapons of mass destruction, and which would go a long way toward removing atomic energy at least as a source of conflict between the powers".

The term was also used in the introduction to the hugely influential US Government Document known as NSC-68 written in April 1950.

During a televised presentation about the Cuban Missile Crisis on 22 October 1962, John F. Kennedy made reference to "offensive weapons of sudden mass destruction. "

An early use of the exact phrase in an international treaty was in the Outer Space Treaty of 1967, however no definition was provided.