In August 1943, the Prime Minister of the United Kingdom, Winston Churchill, and the President of the United States, Franklin D. Roosevelt, signed the Quebec Agreement, which provided for cooperation between the two countries. The Quebec Agreement established the Combined Policy Committee and the Combined Development Trust to coordinate the efforts of the United States, the United Kingdom and Canada. The subsequent Hyde Park Agreement in September 1944 extended this cooperation to the postwar period. A British Mission led by Wallace Akers assisted in the development of gaseous diffusion technology in New York. Britain also produced the powdered nickel required by the gaseous diffusion process. Another mission, led by Oliphant who acted as deputy director at the Berkeley Radiation Laboratory, assisted with the electromagnetic separation process. As head of the British Mission to the Los Alamos Laboratory, James Chadwick led a multinational team of distinguished scientists that included Sir Geoffrey Taylor, James Tuck, Niels Bohr, Peierls, Frisch, and Klaus Fuchs, who was later revealed to be a Soviet atomic spy. Four members of the British Mission became group leaders at Los Alamos. William Penney observed the bombing of Nagasaki and participated in the Operation Crossroads nuclear tests in 1946.

Cooperation ended with the Atomic Energy Act of 1946, known as the McMahon Act, and Ernest Titterton, the last British government employee, left Los Alamos on 12 April 1947. Britain then proceeded with High Explosive Research, its own nuclear weapons programme, and became the third country to test an independently developed nuclear weapon in October 1952.