During the war the ZIS-5 was used on all fronts, where it was greatly appreciated for its remarkably simple and reliable construction. Apart for cargo duties, the ZIS-5 was used as a light artillery tractor and for troops transportation (25 soldiers could seat in five benches placed in the rear body). ZIS-5 served also as base for many special trucks, like refuellers, field workshops, ambulances, portee guns or AA platforms.

After the GAZ-AA, the ZIS-5 was the 2nd most used Red Army truck of 1933-1943 period. The intensive growth of Lend Lease trucks shipping in 1943-1944 did not affected the first line use of the "Tryohtonka" (as soldiers called the ZIS-5 for its 3-ton payload), while GAZ-AA got somewhat phased out to secondary roles.

The ZIS-5 showed remarkable service on the "Road of Life", the only supply line to the besieged city of Leningrad, opened on the frozen surface of the Ladoga Lake in the winter months during 1941–1944.

Set bevat;