She started her service in the Atlantic, but soon she was transferred to the Pacific Fleet, where she cruised all along the West Coast, and took part in most of the pre-war US battle-exercises.

At the time when Pearl Harbor was attacked, she was in the dry dock, missing the action. In the following month she left on numerous sorties, but most of them had been called of, and she did not have too much contact with the enemy. However she got plenty of it in the Battle of the Coral Sea.

She was escorting the Lexington (CV-2), bringing down several attacking Japanese aircraft, but she could not save the carrier, only 112 of her survivors. After the battle she was attached to the destroyer screen of USS Enterprise, but she arrived late to the Midway Islands, and missed the battle. She participated in the landings and the following fierce naval battles around the Solomon Islands.

Later she served in the Northern Pacific, in the invasions of the Aleut-Islands, and as war went on, USS Dewey happened to be present at almost every major American landings, like Kwajalein, Tinian, Saipan, Guam, and performed brilliantly. As a result, she was awarded 13 Battle Stars for her services. She was decommissioned on 19 October 1945, stricken on 1 November 1945 and sold for scrap on 20 December 1946.