Hanscom AFB was created as Bedford Airport, a local civil field for mid-Massachusetts service in 1941, partly as part of a federal program to increase air capacity in the USA. The entry of the US into World War Two created a demand for airports for many services, and Hanscom was quickly acquired by the Army Air Force for fighter training and renamed Bedford Army Air Field. The 85th and 318th Fighter Squadrons trained at Hanscom before being deployed to combat in North Africa and Europe. In 1943 Bedford was renamed Hanscom to honor one of the local citizens killed in an aircraft crash on the trip to the Massachusetts State House to lobby for funds for that very airport.

Late in the war Hanscom was used for testing radar sets developed at MIT. This duty turned out to be the primary function of the base for many years; Hanscom's proximity to MIT and Cambridge made an excellent arrangement for technical support. Radar's importance in modern combat was clear by the end of the war, and Hanscom was not inactivated at the close of the war. Instead, the base expanded, and in the 1950s Hanscom developed critical skills for the creation of the national early detection radar network, SAGE. Increased need for electronic systems fuelled development at Hanscom, and the base's technical staff grew to accommodate increasingly common electronics aviation systems, beginning with the Electronic Systems Division in 1961. This increase in technical support diminished the operational role of Hanscom, and by the mid-1970s the field was reverted to civilian air service; the base was thereafter a non-flying facility.

Aviation's need for electronics system testing has only increased over the last 40 years, and the end of the Cold War did little to check the demand for Hanscom's services. Base realignment has led to administration adjustments, mainly in reassignment to Air Force Materiel Command, but the base continues to play a crucial role, and now houses the 66th Air Base Group, part of the Air Force Life Cycle Management Center, overseeing Air Force weapons systems from inception to retirement. Other notable units at Hanscom include the USAF Band of Liberty, the 66th Medical Squadron, and the 66th Air Base Group Public Affairs.