The M1919 was first developed for infantry use and was later adapted to various other use. The M1919 was to be used on a tripod and was operated by a two or three man team.
M1919: First production model with heavy barrel to mimic characteristics of water cooled M1917.
M1919A1: M1919 with a light barrel that did not make the weapon that easier to carry but impaired the sustained fire ability significantly.
M1919A2: M1919 with a medium thickness barrel that was used between World War 1 and 2. The M1919A3 is similar with detailed differences.
M1919A4: Mass produced improved version of the M1919A2. The A4 model is the most common M1919 variant.

Besides infantry use the M1919 has also been widely employed on vehicles. The M1919 could serve as a pintle mounted weapon or as a bow or coaxial machine gun. The vehicle mounted models are very similar to the M1919A4.
M1919A5: Dedicated vehicle model of the M1919A4 with extended charging handle.
M1919A4E1: An original M1919A4 converted with extended charging handle similar to M1919A5.
M37: Coaxial machine gun model similar to M1919A5 but with ability to feed from both sides. Introduced in 1953.
AN/M2: M1919A4 for aircraft use with thinner barrel and receiver and higher rate of fire. There also is a AN/M2 in 12.7mm that was derived from the M2HB.

The M1919A6 is an infantry model with a bipod and shoulder stock. Therefore there is no need to carry a tripod. In order to keep it man portable it has a lighter barrel to compensate for the added weight of the wooden stock. The M1919A6 was used extensively at the end of World War 2 and the Korean War.

The South African MG4 is an improved M1919. Changes include the use of disintegrating belts, reliability upgrades, open bolt system, a safety system and a quick change barrel. It was available in .303 and .30-06 but the 7.62x51mm version is the one that was mass produced. The MG4 was not produced in an infantry versions. It is only available on flexible mounts as the MG4 AA and as a coaxial weapon on vehicles as the MG4 CA.