On commencement of Operation Barbarossa, the group was a part of Army Group North, and consisted of the XLI and LVI Army Corps (mot.) with three panzer and two motorised infantry divisions equipped with 631 tanks. It spearheaded the advance towards Leningrad, until it was transferred to Army Group Center to help its drive to Moscow.
The 4th Panzer Army, with Heinz Guderian's 2nd Panzer Army, destroyed countless Soviet units until it came to a stand still just outside Moscow.
In 1942 it became part of Army Group B, and some of its divisions, notably, the 24th Panzer Division, were encircled and destroyed at Stalingrad. Under General Hoth, what remained of the army failed in breaking the encirclement of Stalingrad in Operation Wintergewitter, and withdrew, forcing the surrender of the encircled troops.
The army was the southern spearhead in the Battle of Kursk, 5 july 1943. Following this failed offensive, it was pushed back, taking part in the defensive campaign to counter the Red Army's Lower Dnieper Strategic Offensive Operation, before ending the war in Slovakia as part of Army Group Centre.