Trials, fitting out, shakedown, and minor repairs occupied Fanning until 22 April 1938 when she joined Philadelphia (CL-41) at Annapolis, Maryland, to escort the cruiser as she carried Franklin D. Roosevelt, President of the United States on a Caribbean cruise.

After returning to New York on 11 May, she underwent overhaul, escorted MS Kungsholm with Gustaf VI Adolf, the Crown Prince of Sweden, embarked, then sailed for the west coast to join the Battle Force in September.

This combined force, commanded by Vice Admiral William F. Halsey, Jr., and carrying the Doolittle raiders, was charged with launching the first American offensive against the Japanese homeland.

The destroyer made two voyages along the west coast and escorted three convoys to Pearl Harbor before 12 November when she joined TF 11 for duty in the Solomon Islands.

On 19 January 1944 Fanning sailed with TG-58.4 for operations in the Marshalls where planes from Saratoga (CV-3) struck at Wotje, Taroa, Utirik, and Rongelap with a 4-day uninterrupted bombardment of Eniwetok which precursed a later all-out attack.

For the remainder of the month Fanning and other units of the escort group shuttled between Kwajalein and Eniwetok, making 25 strikes in 19 days, and providing support for the amphibious landings on the latter island.

HMS Illustrious and Saratoga launched air strikes against Sabang, Sumatra, (19 April) to destroy refineries, storage and transportation facilities.

Fanning sortied with TG 38.1 on 16 October to screen a carrier group which launched two strikes against Luzon before moving in to support the Leyte landings.

22 October found the group underway for refueling and replenishment at Ulithi but word of an advancing Japanese fleet caused them to reverse course and the destroyer sped to participate in the action at San Bernardino Strait.

She then assumed station as radar picket and air rescue ship, operating also in local escort duty and in training exercises with a submarine wolfpack through 22 March.