Clark's prewar service included operations on the Atlantic coast, in the Caribbean, and from Pearl Harbor, her home port from 1 April 1940.

Clark departed the west coast 27 December, escorted two convoys to Pearl Harbor, then took up antisubmarine patrol off Pago Pago, Samoa, and in February and March 1942 joined a carrier task force for air raids on New Guinea From April through May 1942, Clark escorted four convoys on their passage between Pearl Harbor and San Francisco, California, continuing to Midway on the last.

Between 12 August and 8 September, she sailed out of Nouméa, New Caledonia, screening oilers fueling carrier task forces, and then returned to Auckland for a month of duty escorting convoys from New Zealand to South Pacific island bases.

After a final month of local escort and patrol duty at Nouméa, Clark sailed 11 December 1942 to report at Balboa as flagship for Commander, Southeast Pacific Force.

Between 4 September 1944 and 11 April 1945, she guarded the passage of six transatlantic convoys to ports in the United Kingdom and France.