Most of its work was done with the strictest secrecy, and it began research of what would become some of the most important technology during World War II, including radar and the atomic bomb.

Vannevar Bush, the director of the Carnegie Institution, had pressed for the creation of the NDRC because he had experienced during World War I the lack of cooperation between civilian scientists and the military.

Government officials then complained that Bush was attempting to increase his authority and to bypass them—which he later admitted he was: In his June 15 letter which appointed Bush to the head of the committee, Roosevelt outlined that the NDRC was not meant to replace the research work done by the Army and Navy in their own laboratories or through industry contracts, but rather to "supplement this activity by extending the research base and enlisting the aid of the scientists who can effectively contribute to the more rapid improvement of important devices, and by study determine where new effort on new instrumentalities may be usefully employed."

An Advisory Committee on Uranium had been established to consider the feasibility of an atomic bomb as part of the National Bureau of Standards during 1939 as the result of the Einstein–Szilárd letter, but had not made significant progress.

It was instructed in Roosevelt's June 15 letter to report to the NDRC and Bush, establishing the chain of command which would later result in the full-scale bomb project.

The NDRC of the OSRD membership consisted of Conant (Chairman), Tolman (Vice-Chairman), Adams, Compton, and Jewett, along with the Commission of Patents (Coe until September 1945, and then Casper W. Ooms), and the representatives of the Army and Navy (which changed periodically).

During early June 1941, shortly before it was superseded by the OSRD, its organization was as follows: The Committee on Uranium, chaired by Lyman Briggs, reported directly to the Chairman of the NDRC and as such does not appear in the chart above.