From May 1942 onwards, it was employed in battles on the Eastern Front as a part of the 6th Army under the command of General der Panzertruppe Friedrich Paulus.

The German troops could repel the attack and conducted a successful counter-offensive, during which they encircled the Soviet formations.

The 389th Infantry Division also participated in the German summer offensive Operation Blau, which had the aim to capture the Caucasus and Stalingrad.

During the Battle of Stalingrad, the 389th Infantry Division was the main force of the failed attack on the tractor factory.

During the Soviet counter-offensive beginning under the codename Operation Uranus on 19 November 1942, the division's remnants were captured after the Axis capitulation on 2 February 1943.

ID was reformed in Hungary in March 1944 and employed as part of Army Group North in the Kurland Pocket, where it fought until February 1945.