Departing Norfolk, Virginia, on 14 October 1922, she cruised primarily in the Eastern Mediterranean, putting in at ports in Turkey, Bulgaria, Russia, Egypt, Palestine, Syria, Greece, and Romania.

The presence of U.S. Navy warships amidst this tension assisted various relief agencies working to mitigate the damage from past and present wars as well as protect American lives, interests, and property.

This established pattern of coastwise exercises and fleet maneuvers was broken in the fall of 1926, as Goff and the light cruiser USS Milwaukee (CL-5) engaged in rescue work on the Isle of Pines off Cuba, which had been devastated by the 1926 Havana–Bermuda hurricane of 19–20 October 1926.

From Nicaragua, Goff returned to her regular routine along the U.S. East Coast, tactical exercises spiced by winter maneuvers in the Caribbean, a pattern to which she held for several years.

Departing Cuba on 2 April 1934, Goff resumed maneuvers along the U.S. East Coast until 9 November 1935, when she joined the United States Pacific Fleet at San Diego, California.

She remained in the Pacific, operating along the United States West Coast and taking part in exercises in Hawaii until 4 January 1939, when she departed San Diego for New York City.

Arriving there on 20 April 1939, Goff again cruised the U.S. East Coast training Naval Reserve personnel until 8 September 1939, when she entered New England waters to serve on the Neutrality Patrol.

She and Barry convoyed the seaplane tender USS Albemarle (AV-5), loaded with aeronautical supplies and personnel, from Norfolk to Casablanca and then on to Reykjavík, Iceland, returning to New York City on 31 December 1943.

Goff spent the first seven months of 1944 with Albemarle, shepherding the seaplane tender safely to San Juan, Trinidad; Casablanca; Recife, Brazil; and Avonmouth, England, before putting in at Boston, Massachusetts, on 13 July 1944 for overhaul.

At Key West, she was attached to the Fleet Sound School and served in a variety of duties, including antisubmarine work, harbor guard, and target vessel for ships and planes in training.