She was sponsored by Miss Sarah Babbitt, a descendant of Commodore of the Continental Navy Esek Hopkins; and commissioned 21 March 1921 at Philadelphia.

For the next seven years, Hopkins operated out of New England ports in the summer, Charleston, South Carolina, in the winter, and the Caribbean Sea in the spring.

Hopkins returned to Norfolk, Virginia in April 1939, and performed Neutrality Patrol from September 1939 until sailing for San Diego 37 May, and from there to Pearl Harbor.

When the Japanese attacked Pearl Harbor, Hopkins was at Johnston Island for war maneuvers, but immediately headed back to Hawaii.

She continued patrol of the Hawaiian Sea Frontier, with a short break for overhaul in the States, until late summer 1942, when she joined the invasion fleet bound for Guadalcanal.

As America's first offensive of the Pacific war began 7 August, Hopkins swept the transport area and covered the landings on Tulagi.

As the Navy moved farther across the Pacific in the island-hopping campaign, Hopkins arrived off Saipan 13 June 1944 to sweep the invasion approaches.

Hopkins departed the Philippines 15 January 1945 for a brief rest at Eniwetok, then swept the transport areas and channels off Iwo Jima to prepare for invasion 19 February 1945.

Hopkins rode out two typhoons with winds raging to 125 knots before her departure from Tokyo Bay 10 October 1945 for the Eastern Seaboard of the United States.