Following her shakedown cruise, Biscayne joined the Atlantic Fleet and operated out of Boston, Massachusetts, on patrol and plane guard missions from 7 December 1941 until 27 May 1942.

Biscayne departed Norfolk, Virginia, on 17 October 1942 and, after a short stop at Guantanamo Bay, Cuba, moved to Freetown, Sierra Leone, with Patrol Squadron 92 (VP-92), arriving on 2 November 1942.

Biscayne moved to Casablanca, French Morocco, on 18 November 1942 and remained there until 25 April 1943 supporting patrol squadrons.

Biscayne arrived at Mers-el-Kebir, Algeria, on 26 April 1943 and became the flagship of Rear Admiral Richard Lansing Conolly, Commander, Landing Craft and Bases, Northwest African Waters.

While at Mers-el-Kebir she was fitted out as an amphibious force flagship by repair ship USS Delta (AR-9) between 2 and 31 May 1943, although she retained her seaplane tender classification and AVP-11 designation for the time being.

Departing Bizerte on 10 July 1943, Biscayne served as flagship of the Joss (Licata) Force in Operation Husky, the Allied invasion of Sicily.

One time the admiral wanted to get a closer look at the beach at night and search lights lit them up "like a Christmas tree", according to Avery.

Sailing for Italy once again, she served as flagship during Operation Shingle, the Allied landings at Anzio, from 22 January 1944 to 2 February 1944.

She arrived at Pearl Harbor, Hawaii, on 9 January 1945 and became flagship of Captain Frederick Moosbrugger, Commander, Destroyer Squadron 63.

she carried out similar duties during Operation Iceberg, the landings on Kerama Retto on 26 March 1945 and on Okinawa on 1 April 1945.

Biscayne the Navy Unit Commendation for meritorious service in action against enemy aircraft, shore batteries, surface forces and mines in both the European and Pacific Theaters of Operation.

Barnegat-class ships were very reliable and seaworthy and had good habitability, and the United States Coast Guard viewed them as ideal for ocean station duty, in which they would perform weather reporting and search-and-rescue tasks, once they were modified by having a balloon shelter added aft and having oceanographic equipment, an oceanographic winch, and a hydrographic winch installed.

Dexter transferred a life raft and damage control timbers to Louisburg and escorted her safely to St. John's, Newfoundland.

On 4 November 1948, while underway from Ocean Station Alfa, Dexter assisted the fishing vessel Pan Pades Andros, which was disabled about 30 nautical miles (56 km) southeast of Sable Island.

On 19 February 1952, Dexter left Ocean Station Hotel to assist the merchant ship SS Helen Stevenson, which had cracked across the main deck port and starboard at the hatch.

She escorted Helen Stevenson to a point less than 10 nautical miles (18.5 kilometers) east of St. George's, Bermuda, and then returned to station.

Recruits spent approximately three months aboard Dexter for indoctrination and one extended cruise beyond the waters of San Francisco Bay.

Dexter also made cruises to various ports on the U.S. West Coast, as well as to British Columbia in Canada, Hawaii, Alaska, and Mexico, in connection with training activities.

On 18 July 1959, she towed the disabled fishing vessel Cloud Nine until relieved by the Coast Guard buoy tender USCGC Blackhaw (WLB-390).

In early February 1966, she towed the disabled sloop Allegro from 360 nautical miles (670 km) south-southwest of San Diego, California, to Asuncion Bay.