Goldsborough was reactivated for World War II and was used as an aircraft tender, destroyer and high speed transport in both Atlantic and Pacific theaters.

Goldsborough joined Division 25, Squadron 3, U.S. Atlantic Fleet, departing Norfolk 25 February 1920 for training at Guantanamo Bay, Cuba, and returning to New York City on 1 May 1920 for maneuvers and tactics off the New England Coast.

She stood out of Hampton Roads on 1 September 1920 on a practice cruise in the Gulf of Mexico, returning to Norfolk on 10 October for operations along the seaboard to New York until 5 January 1921 when she sailed to join the combined Battle Fleet off Cuba; thence she steamed through the Panama Canal to Callao, Peru, and back to Guantanamo Bay for further battle practice before return to Norfolk on 27 April.

Goldsborough departed New York on 12 August 1940, to tend amphibious planes on Neutrality Patrol in waters ranging from Puerto Rico, Cuba, and the United States Virgin Islands, to Trinidad, British West Indies.

Near midnight of 2 January 1944, she made visual contact with a surfaced U-boat off the Azores, fought through heavy seas in an attempt to ram amidships.

Goldsborough departed Charleston on 10 April and reached Pearl Harbor, via the Panama Canal and San Diego on 9 May for amphibious assault training in Hanalei and Kawaihae Bay.

She departed Saipan on 28 July to train Underwater Demolition Team 4 in Hawaiian waters, then joined a Beach Demolition Task Group that sailed from Manus, Admiralty Islands, on 12 October to destroy enemy facilities and installations in the vicinity of the proposed invasion beaches of eastern Leyte as well as on the entrance islands of Leyte Gulf.

She again arrived off Noemfoor on 19 December for transport of troops to Mios Woendi, Padiados Islands, and thence via Morotai with six merchant ships escorted into Leyte Gulf 6 January 1945.

She dispatched a medical team to damaged destroyer escort Gilligan on 12 January, picked up two survivors, and then defended against a kamikaze which just missed the stern of Seusens before crashing into the sea.

Her name was struck from the Navy List 24 October 1945 and she was sold for scrapping 21 November 1946 to Hugo Nuef Corporation, New York City.