The new division was part of Operation Barbarossa which began in June 1941, suffering such heavy casualties in the first two months that one of its three tank battalions had to be disbanded by August.

The division took part in the advance in the central sector of the Eastern Front and participated in the Battle of Moscow.

The 19th Panzer Division remained in the central sector until late 1942, when it was sent south to support the Italian 8th Army.

The division took part in defensive battles after the collapse of the German southern front following the encirclement of the 6th Army at Stalingrad.

It participated in the unsuccessful German offensive during the Battle of Kursk, suffering heavy casualties while operating in the area of Belgorod.