Over twenty variants of the North American P-51 Mustang fighter were produced from 1940, when it first flew, to after World War II, some of which were employed also in the Korean War and in several other conflicts.

The prototype of the Mustang, designated NA-73X, was rolled out by North American Aviation on 9 September 1940, albeit without an engine, and was first flown the following 26 October. The Mustang was originally designed to use a low-altitude rated Allison V-1710 engine. Unlike later models, Allison-powered Mustangs were characterized by the carburetor air intake placed on the dorsal surface of the nose, immediately behind the propeller.

The first production contract was awarded by the British for 320 NA-73 fighters, named Mustang Mk I by the British Purchasing Commission; a second British contract soon followed, which called for 300 more (NA-83) Mustang Mk I fighters. Contractual arrangements were also made for two aircraft from the first order to be delivered to the USAAC for evaluation; these two airframes, 41-038 and 41-039 respectively, were designated XP-51. The first RAF Mustang Mk Is were delivered to 26 Squadron at RAF Gatwick in February 1942 and made their combat debut on 10 May 1942. With their long range and excellent low-altitude performance, they were employed effectively for tactical reconnaissance and ground-attack duties over the English Channel, but were thought to be of limited value as fighters due to their poor performance above 15,000 ft (4,600 m).

RAF Mustangs (Mk Is, which were not drop tank capable) made history on October 22, 1942, when they escorted 22 Vickers Wellington medium bombers on a daylight raid to Germany, thus becoming the first RAF single-seat fighters to fly over the country during World War II.

The first American order for 150 P-51s, designated NA-91 by North American, was placed by the US Army on 7 July 1940. This was on behalf of the RAF in a Lend-Lease deal. All but the last 57 went to the British. After the attack on Pearl Harbor, the USAAF 'held back' these Mustang Mk IAs for their own use. Fifty-five of these P-51-1s were outfitted with a pair of K.24 cameras in the rear fuselage for tactical low-level reconnaissance and re-designated F-6A (the "F" for photographic, although confusingly also still referred to as the P-51 or P-51-1). Two kept their P-51-1 designation and were used for testing by the USAAF.^{[clarification needed]}

Two XP-51s (serials 41-038 and 41-039) set aside for testing arrived at Wright Field on 24 August and 16 December 1941 respectively. The small size of this first order reflected the fact that what had been known as the USAAC up until late June 1941 was still a relatively small, underfunded peacetime organization. After the late-June 1941 reorganization of the USAAC into the United States Army Air Forces, roughly six months before the attack on Pearl Harbor changed the outlook for the United States regarding involvement in global hostilities against the Axis overnight, priority had to be given to building as many existing fighters – P-38s, P-39s, and P-40s – as possible while simultaneously training pilots and other personnel, which meant evaluation of the XP-51 did not begin immediately. However, this did not mean it was neglected, or testing and evaluation mishandled.

The 150 NA-91s were designated P-51 by the newly formed USAAF and were initially named Apache, although this was soon dropped and the RAF name, Mustang, adopted instead. The USAAF did not like the mixed armament of the British Mustang Is and instead adopted an armament of four long-barrelled 20 mm (.79 in) Hispano Mk II cannon, removing the .50 cal (12.7 mm) "nostril"-mounted weapons. The British designated this model as Mustang Mk IA, and would fit a number with similar equipment.

It was quickly evident the Mustang's performance, although exceptional up to 15,000 ft (4,600 m) (the supercharger's critical altitude rating), was markedly reduced at higher altitudes. This was because the single-speed single-stage supercharger fitted to the V-1710 had been designed to produce maximum power at low altitude; above that, power dropped off rapidly. Prior to the Mustang project, the USAAC had Allison concentrate primarily on turbochargers in concert with General Electric; the turbochargers proved to be reliable and capable of providing significant power increases in the Lockheed P-38 Lightning and other high-altitude aircraft, in particular in the Air Corps' four-engine bombers. Most of the other uses for the Allison were for low-altitude designs, where a simpler supercharger would suffice. Fitting a turbocharger into the Mustang proved impractical, and Allison was forced to use the only supercharger available. In spite of this, the Mustang's advanced aerodynamics showed to advantage, as the Mk I was about 30 mph (48 km/h) faster than contemporary Curtiss P-40 Warhawks using the same V-1710-39 (producing 1,220 hp (910 kW; 1,240 PS) at 10,500 ft (3,200 m), driving a 10 ft 6 in (3.20 m) diameter, three-blade Curtiss-Electric propeller). The Mk I was 30 mph (48 km/h) faster than the Supermarine Spitfire Mk Vc at 5,000 ft (1,500 m) and 35 mph (56 km/h) faster at 15,000 ft (4,600 m), despite the British aircraft's more powerful engine (the Rolls-Royce Merlin 45, producing 1,470 hp (1,100 kW; 1,490 PS) at 9,250 ft (2,820 m).