The concept of joining two aircraft together to provide more power or space was not new when development of the North American Twin Mustang began in 1944. It had already been used with some success by the five-engined Heinkel He 111Z and by the General Aircraft Twin Hotspur glider.

The Mustang development came as a result of the USAAF requirement for a very long-range escort fighter for Pacific operation. The purpose of having two pilots was as a relief against fatigue on the long overwater missions. To help combat such fatigue, adjustable seats were fitted and there was also provision for uncoupling the rudder pedals. A complete control system was available in each cockpit, although full flight instruments were only fitted in the port fuselage.

The first two prototype XP-82s flown in 1945 had two Packard Merlin V-1650 engines with counter-rotating propellers, while the third XP-82 had two Allison V-1710s with common rotation. It was a variant of the latter engine that was chosen for production aircraft.

A large USAAF order for 500 P-82Bs was placed, but only 20 had been built when the end of World War II resulted in large-scale cancellations of contracts. The tenth and eleventh production aircraft were converted to night fighters as the P-82C (SCR-720 radar) and P-82D (APS-4 radar) respectively, the radar being carried in a large nacelle beneath the centre section, while the radar operator was carried in a modified starboard cockpit.

The P-82 was reinstated in 1946 USAAF order books with a batch of 250, comprising 100 P-82E escort fighters, 100 P-82F night fighters (APS-4 radar) and 50 P-52Gs (SCR-720 radar). A change of USAF designations in 1948 led to the models B to G becoming F-82s, and by December of that year the type had completely replaced the Northrop P-61 Black Widow. Following deployment to Japan, F-82s of the US 5th Air Force were among the first USAF aircraft to operate over Korea, and a pilot from the 68th Fighter (All-Weather) Squadron based at Itazuke shot down the first enemy aircraft in the Korean War.