With assistance from firearms engineers at Fabrique Nationale de Herstal  Belgium, the Model 1919 was completely re-engineered into the .30 calibre M2 AN (Army-Navy) aircraft machine gun . The .30 in M2 AN Browning was widely adopted as both a fixed (offensive) and flexible (defensive) weapon on aircraft. Aircraft machine guns required light weight, firepower, and reliability, and achieving all three goals proved a difficult challenge. The receiver walls and operating components of the M2 were made thinner and lighter, and with air cooling provided by the speed of the aircraft, designers were able to reduce the barrel's weight and profile. As a result, the M2 weighed two-thirds that of the 1919 A4, and the lightened mechanism gave it a rate of fire approaching 1,200 rpm (some variants could achieve 1,500 rpm), a necessity for engaging fast-moving aircraft. The M2's feed mechanism had to lift its own loaded belt out of the ammunition box and feed it into the gun, equivalent to a weight of 11 lb (5 kg). In Ordnance circles, the .30 M2 AN Browning had the reputation of being the most difficult-to-repair weapon in the entire US small arms inventory.

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The M2 also appeared in a twin-mount version which paired two M2 guns with opposing feed chutes in one unit for operation by a single gunner, with a combined rate of fire of 2,400 rpm. All of the various M2 models saw service in the early stages of World War II, but were phased out beginning in 1943, as hand-trained defensive machine guns became obsolete for air warfare (the .50 in/12.7 mm M2 Browning and 20 mm automatic cannon had replaced the .30 in as offensive air armament as well). The .30 in M2 aircraft gun was widely distributed to other US allies during and after World War II, and in British and Commonwealth service saw limited use as a vehicle-mounted anti-aircraft or anti-personnel machine gun.

The same basic weapon was also chambered for the British .303 round, and was used as aaircraft gun in fighters and bombers such as the Spitfire and Lancaster.