"Dzerzhinsky" was part of the 1st Destroyer Division of the fleet at Batumi along with "Frunze" by 22 June 1941, when the Germans invaded of the Soviet Union. Between 22 and 25 June she laid 240 mines off the Batumi Naval Base in four night sorties. With her sisters, she was sent to support the defenders during the Siege of Odessa due to a fleet prohibition on using large ships after the Raid on Constanța that was in effect until August, forcing the elderly "Novik"s to be employed. "Dzerzhinsky" arrived in Odessa on 20 August with a cargo of ammunition, and on the next day bombarded Dofinovka, firing 88 102 mm shells. On the thirteenth volley the elevator of one turret failed and it had to be reloaded by hand. She was attacked without result by three Heinkel He 111 bombers, one of many air attacks on the Soviet ships supporting Odessa. The destroyer escorted three transports out of Odessa on 23 August, and departed Sevastopol on 29 August escorting three transports, together with two minesweepers and three torpedo boats. Arriving at Odessa on the next day, she bombarded Fontanka, expending 200 shells. While engaged in this duty, the destroyer was attacked several times by Axis aircraft without result. After maneuvering in the Gulf of Odessa during the night, "Dzerzhinsky" expanded another 118 shells against Fontanka and other Axis positions during the next day, and left Odessa that night with a tugboat that towed two barges. The slow speed of the latter forced the destroyer to travel at , delaying her return to Sevastopol until 2 September.