The weapon was developed as a private venture by the company in 1940 and was submitted to the Reichsluftfahrtministerium (RLM - Reich Aviation Ministry) in response to a 1942 requirement for a heavy aircraft weapon for use against the Allied bombers appearing en masse in German skies. Testing verified that the cannon was well-suited to this role, requiring as little as five hits with high-explosive ammunition to bring down a heavy bomber such as a B-17 Flying Fortress or B-24 Liberator. The MK 108 was quickly ordered into production and was installed in a variety of Luftwaffe fighter aircraft, including the Messerschmitt Bf 109, Focke-Wulf Fw 190, Heinkel He 219, Messerschmitt Me 163, and Messerschmitt Me 262. Apart from the high-explosive (or "mine" round), incendiary rounds were also produced for it.
The cannon proved to be very effective and reliable, its main shortcoming only that its shells arced too much due to its low muzzle velocity, making aiming more difficult. Otherwise, it was simple to manufacture and maintain and its compact size and weight made it ideal for aircraft installation. The cannon's distinctive heavy pounding sound gave it the nickname pneumatic hammer amongst Allied aircrews.
The MK 108 was also fitted to night fighters in an unusual installation, called "Schräge Musik" (German: "Jazz Music", literally "slanting music" ). In this configuration, the cannons were mounted in the fuselage, aiming upwards at an almost vertical angle. This allowed the night fighter to attack a bomber by making a high-speed pass underneath the enemy aircraft.