Prototypes were made in 1931, serial production started in 1933, lasted until October 1941 at the Moscow Zavod imeni Stalina factory and a total of 21,239 units were produced.

A reliable truck, it served as a base for the creation of a number of specialized military modifications -- searchlight truck, radio and radio repair station, mobile field workshop, supply delivering vehicle, troops moving vehicle, and as an artillery towing vehicle -- but is best known for its role as the first multiple rocket launcher (Katyusha) in July 1941.

It was built by the "Compressor" Plant's Design Office during World War II (1941–45).

During the early World War II, the ZIS-6 was used as the chassis of the original BM-13 Katyusha multiple rocket launcher by the Red Army, nicknamed "Stalin's Organ" by German soldiers.

Later though, the American-produced Studebaker took over as the predominant platform for Katyusha launchers.