When Operation Barbarossa began on 22 June 1941, then-Major Seryugin commanded the regiment on the Southwestern Front, leading it in the Border Battles west of Stanislav and in the Vinnytsia sector south of Uman. In September he was assigned command of the 124th Rifle Division but did not actually take command due to the 124th being caught in encirclement. Seryugin was instead appointed chief of staff of the 212th Rifle Division, with which he fought in the Donbass Defensive and Barvenkovo–Lozovaya offensive as part of the 6th Army of the Southwestern Front. In May 1942 then-Colonel Seryugin was appointed deputy commander of the division, while continuing to serve as its chief of staff. He fought with it in the Second Battle of Kharkov, during which the division was surrounded. In early June Seryugin broke out of encirclement and crossed over to the eastern bank of the Seversky Donets with the remnants of the 212th.