After a period at Norfolk, Virginia, as training ship for crews for escorts soon to be commissioned, Fessenden carried out an escort mission to the Panama Canal Zone, returning to Norfolk 5 November 1943. Between 23 November and 18 March 1944, she escorted convoys on two voyages to Casablanca, then on 3 April sailed again to guard a convoy to Bizerte. Off Bone 20 April the convoy came under heavy air attack, one guardian destroyer being sunk, and on the homeward bound passage, the convoy screen lost two more destroyers to submarine attack. Fessenden returned safely to New York 21 May. She sailed from Norfolk next on 12 June 1944, and escorted a convoy as far as Gibraltar, where she was detached to escort two captured Italiansubmarines to Bermuda. One developed engine trouble 2 July and was ordered back to Gibraltar, but Fessenden reached Bermuda with the other 16 July. Returning to New York 22 July, she was briefly overhauled, then sailed out of New London, Connecticut, training submarines from 3 August to 2 September. Next came special training off Maine, and her return to Norfolk to join the hunter-killer group formed around.
Operating with this group south of the Cape Verde Islands on 30 September 1944, Fessenden and two other ships investigated a contact, making a depth charge attack late in the afternoon, sinking U-1062 in. The group continued its antisubmarine patrols in the South Atlantic refueling at Dakar, French West Africa, Bahia and Recife, Brazil, and Cape Town, South Africa. Fessenden returned to New York 26 November, joined in training exercises in Long Island Sound, then off Guantánamo Bay, until 19 January 1945 when she reported to Miami, Florida, to serve as school ship for the Naval Training Center for a month. She returned to Guantanamo 12 February 1945 to rejoin the Mission Bay group as it provided air cover for a convoy northeast of Bermuda carrying President F. D. Roosevelt home from the Yalta Conference. After brief overhaul at New York, she sailed north to Argentia, Newfoundland, with her hunter-killer group to work with similar task organizations in setting up a barrier patrol in the North Atlantic, to prevent German submarines from approaching the United States during the last days of the European war.
Fessenden was converted for radar picket duty at Boston, Massachusetts, where she was recommissioned 4 March 1952. After antisubmarine training out of Key West, Florida, Fessenden returned to her home port, Newport, Rhode Island, 25 September 1952 to begin duty on the radar picket stations of the North Atlantic. She returned from her sea patrols only for necessary maintenance and refresher training. With her division, she sailed from Newport 15 July 1957 for Pearl Harbor, her home port for Pacific early warning radar picket duty from 18 August 1957 until 18 March 1960 when she left the Hawaiians for San Francisco, California.