She arrived at Devonport, England, on 16 June and shifted to Harwich two days later before subsequently calling at Heligoland, Germany; Copenhagen, Denmark; and the free city of Danzig.

Assigned to the Pacific Fleet soon thereafter, Upshur transited the Panama Canal, bound for San Diego, her base of operations until the spring of the following year.

At Hankou when the incident occurred, Upshur, acting under urgent orders, got underway for the trouble spot on 22 June—departing with such great haste that four of her complement (one officer and three enlisted men) were left behind.

Upshur conducted exercises in the Philippine Islands in the winter and in Chinese waters, off Yantai, in the summer, with more training and "showing the flag" cruises in between.

Recommissioned on 2 June 1930, Upshur operated with the Battle Fleet and Scouting Force, first on the west coast and later on the east, until decommissioned on 22 December 1936 at Philadelphia.

In the event of such an invasion, Upshur and her sisters in Destroyer Squadron 30 were slated to screen the counter-battery and gunfire support group built around Texas, Vincennes, and Chester.

On 23 December 1940, the heavy cruiser Tuscaloosa departed Norfolk with William D. Leahy, Ambassador to Vichy France, and his wife, embarked, bound for Lisbon, Portugal.

Over the ensuing months, Upshur operated alternately out of Naval Station Argentia, Newfoundland; Newport, Rhode Island; Philadelphia; Narragansett Bay; Boston; and Reykjavík, Iceland, after its occupation by the United States that summer.

Five days later HX 150, a convoy of 50 merchantmen of British and Allied nationalities put to sea from Halifax, Nova Scotia, escorted locally by Canadian units.

On 17 September, about 150 miles (240 km) out of Argentia, the American escort group under Captain Morton L. Deyo, which included Upshur, met up with the British convoy.

In the period following full-scale American entry into the war with the Japanese attack on Pearl Harbor on 7 December 1941 and until the middle of February 1942, Support Force destroyers escorted a dozen convoys in each direction across the Atlantic—750 ships—in comparative safety.

On the night of 4 February 1942, Upshur departed Londonderry Port, Northern Ireland, in company with Gleaves, Dallas, Roper, and the United States Coast Guard Treasury-class cutter USCGC Ingham.

Her duties took her from the eastern seaboard of the United States to the mouth of the Mediterranean Sea, from the inhospitable climes of the North Atlantic to the tropical Caribbean.

As the Allies slowly gained the upper hand in the Battle of the Atlantic, newer and more modern destroyers replaced the aging flush-deckers as front line convoy escorts.

Throughout 1944, Upshur operated between Norfolk, Virginia, and Quonset Point, Rhode Island, serving as plane guard and target vessel during qualification trials for aircraft carriers.

Reclassified as a miscellaneous auxiliary, AG-103 on 3 June 1945, Upshur was plane-guarding for Lake Champlain when Japan capitulated on 15 August, ending the war in the Pacific.