After her shakedown cruise, the new boat conducted training exercises out of New London, Connecticut until getting underway on 26 October 1937 and heading, via Guantánamo Bay, Cuba to transit the Panama Canal on 9 November.

Joining the Pacific Fleet, Pickerel operated out of San Diego, California, along the West Coast, and in Hawaiian waters.

She tracked a Japanese submarine and a destroyer but lost them in haze and rain squalls before they came in torpedo range.

During the refit, LCDR Bacon was detached and Pickerel's executive officer, Lieutenant Commander Augustus H. Alston, Jr., became her new CO. On her sixth war patrol (22 January–3 March 1943), she searched among the Kurile Islands on the Tokyo-Kiska traffic lanes.

Those records also describe an action off Shiramuka Lighthouse on northern Honshū on 3 April 1943[11] in which naval aircraft first bombed an unidentified submarine, then directed Shiragami and Bunzan Maru to the spot, where they dropped twenty-six depth charges.