After the beginning of Operation Barbarossa on 22 June 1941, the division as took up defensive positions on the eastern bank of the Shchara River in the Slonim area on the next day as part of the 13th Army. From 24 June it fought in heavy defensive battles, retreating to Baranovichi, Slutsk, Osipovichi, the village of Boyarshchina, and Starye Dorogi. The division was encircled in late June but broke out on 7 July and was withdrawn to Novozybkov for replenishment. The 121st soon returned to the front and fought in the Battle of Smolensk with the 13th Army of the Central Front, then fought in defensive battles on the Sozh, Sudost, and Desna, and from 30 September in the Battle of Bryansk following the commencement of Operation Typhoon, the German attack that began the Battle of Moscow. During this period, the 121st was encircled for the second time in area of Khutor Mikhailovsky and the Kinelsky forest, but broke out in the area of Pesochnaya and Lgov. The division went on to fight in the defense of Tim and the Yelets Offensive, and was withdrawn to the Southwestern Front reserve in the Yelets area on 15 December.