During her first year of service, Bristol operated as a patrol and convoy escort ship in the North Atlantic, making several trans-Atlantic voyages to Ireland. On 24 October 1942 she made her first voyage to North Africa to take part in the landings at Fedhala, French Morocco (8–17 November). Returning to the United States in late November, she operated out of Norfolk until 14 January 1943, when she again steamed to the Mediterranean where, with the exception of one trip to the Canal Zone in April 1943, she served exclusively until 13 October 1943.
While on duty in that area, she took part in the Sicilian invasion (9 July-17 August 1943) and the Salerno landings (9–21 September). On 11 September 1943 Bristol rescued 70 survivors from the torpedoed Rowan (DD 405).
At 0430 on 13 October 1943, while escorting a convoy to Oran, Algeria, Bristol was struck by an enemy torpedo on the port side at the forward engine room, causing the ship to break in half. Only one explosion occurred. No fires resulted but steam, electrical power and communications were lost and the ship had to be abandoned. Eight minutes after the explosion, the after section sank and four minutes later, the bow section went down. Bristol suffered the loss of 52 of her crew. The survivors were rescued by Trippe (DD 403) and Wainwright (DD 419).
Bristol earned three battle stars for her World War II service.