From 21 April-3 October 1938, and from 4 January 1939 – 27 June 1940, she returned to the Caribbean to conduct off-shore patrols and good will visits, and on the second trip she served as flagship.

Along with her escort and patrol duties, she carried out such missions as landing reconnaissance parties, aiding stricken ships, and taking part in the operations at Attu Island, which was assaulted on 11 May 1943.

Two days later, Charleston arrived to bring her firepower to support Army troops ashore, bombarding Chichagof Harbor, Alaska, and screening the transports lying off the island.

During the attack of Japanese bombers on 22 May, she evaded aerial torpedoes by radical maneuvering, while splashing one enemy plane and helping to drive off the others.

Charleston was anchored nearby a US Army barge at Tanaga Bay, Andreanof Islands, Aleutian Islands, US Territory of Alaska, when on the evening of 16 August 1944 her crew observed the crash of a US Army Air Force North American B-25D Mitchell bomber (serial number 41-29753) aircraft into the bay, about four miles west from the ship.