She served for several months with the American Relief of Armenia and visited several ports in Turkey and the Middle East before sailing eastward late in 1921, to the Orient to commence her four-year tour of duty with the Asiatic Fleet.

Thereafter, she served a two-year tour with United States Naval Forces Europe, and carried out several goodwill visits to many European ports.

In the small hours of 11 December 1937 the ocean liner SS President Hoover ran aground in a typhoon on Kasho-to, east of Formosa.

[2] The two destroyers struggled through heavy seas at only 12 knots (22 km/h) and did not arrive until 1245 hrs the next day, by which time Hoover's 330 crew were most of the way through getting their 503 passengers and themselves ashore safely.

[2] On 7 December 1941, Barker was at Tarakan, Borneo, and upon receipt of the news of the Pearl Harbor attack, immediately commenced patrolling the surrounding area.

On 27 June, as a member of the hunter killer TG 21.12 (Core group), she departed New York to search for enemy submarines in the Atlantic.

The remainder of Barker's active service was performed as a convoy escort in the Caribbean, to Newfoundland, and along the eastern seaboard of the United States.