After shakedown training out of the Virginia Capes, Gamble sailed from New York City on 13 January 1919 to take part in maneuvers off Cuba; Key West, Florida; and the New England seaboard until June 1919.

In October 1920, she came out of reserve and assisted the flotilla in torpedo practice; maneuvered with the Battle Force; and cruised along the California coast as a training ship for reservists.

Recommissioning on 25 September 1939 as Europe was plunged into World War II, she joined Mine Division 5 in patrol and schoolship duties out of San Francisco.

On 7 December 1941, Gamble had returned from offshore patrol, when her peaceful routine was broken by the first of the Japanese carrier-based planes which attacked American ships in the harbor.

Returning to Pearl Harbor for heavier armament, Gamble helped safeguard convoys to Midway during the time of that crucial and historic battle, then headed south with Breese and Tracy to lay a defensive minefield off the entrance to Second Channel, Espiritu Santo, New Hebrides Islands.

Five minutes after midnight on 6 May 1943, Gamble, with Preble and Breese, turned simultaneously in rain squalls which broke at times to disclose each to the other in perfect formation.

The ships then sped north to join the protective screen of Rear Admiral Walden L. Ainsworth's cruiser-destroyer force before refueling at Tulagi.

Aircraft, alerted by a coastwatcher, intercepted the rescue operation, sinking the two destroyers and sending Michishio limping back to port, badly damaged.

After overhaul and refresher training, Gamble departed San Diego on 7 January 1945, en route via Hawaii and the Marshalls to Iwo Jima where she arrived on 17 February, to lend fire support to the various sweeping units, and to explode floating mines.

Both firerooms immediately flooded and she became dead in the water with two holes in her bottom as all hands fought raging fires, jettisoned topside weight and shored damaged bulkheads.