In the years that preceded World War I, Fanning took part in the training schedule of the Atlantic Fleet, sailing to the Caribbean for winter maneuvers, and exercising off the coast of New England in the summers. Based at Norfolk during the major portion of each year, she joined in gunnery practice in this area.
As war raged in Europe, Fanning intensified her preparations for any eventuality. When two German auxiliary cruisers visited Norfolk in September 1916, Fanning acted as part of their escort while they sailed in United States territorial waters. On 8 October 1916 Fanning put out of Newport, Rhode Island to search for the crews of ships sunk not far from Nantucket Light Ship by the German submarine U-53. The destroyer recovered six survivors and landed them at Newport the next day. The presence of U-53 led to the speculation that a secret German submarine base might exist in the Long Island Sound–Block Island Sound area; Fanning searched from 12 to 14 October for evidence of such a base but found nothing and returned to her regular operating schedule.
During the latter half of October 1916, Fanning and the fuel ship Jason conducted experiments to develop methods of oiling at sea, a technique which has since given the United States Navy unbounded mobility and sea-keeping qualities. Torpedo and gunnery practices, and fleet maneuvers during the next 8 months sharpened Fanning’s war-readiness so that, true to Navy tradition, she was able to sail for distant service when called on in June 1917.
Based at Queenstown, Ireland, Fanning and her sister destroyers patrolled the eastern Atlantic, escorting convoys and rescuing survivors of sunken merchantmen. On the afternoon of 17 November 1917 an alert lookout on board Fanning sighted the periscope of U-58, and the destroyer quickly moved in on the attack. Fanning’s first depth charge pattern scored and as Nicholson (DD-52) joined the action, the submarine broke the surface, her crew pouring out on deck, hands raised in surrender. Fanning maneuvered to pick up the prisoners as the damaged submarine plunged to the bottom, the first of two U-boats to fall victim to United States Navy destroyers in World War I.
Fanning continued escort and patrol duty for the duration of the war. Though she made numerous submarine contacts, all of her attacks were inconclusive. On many occasions she went to the aid of torpedoed ships, rescuing survivors and carrying them into port. On 8 October 1918, she picked up a total of 103 survivors, 25 from a merchantman and 78 from the French cruiser Dupetit-Thouars.
Fanning passed in review before President Woodrow Wilson on board transport George Washington in Brest Harbor on 13 December 1918, then remained at Brest until March of the following year. After a quick voyage to Plymouth, England, Fanning departed Brest for the States by way of Lisbon, Portugal and Ponta Delgada, Azores in company with several other destroyers, and escorting a large group of submarine chasers. Fanning was placed out of commission at Philadelphia on 24 November 1919. On 7 June 1924 she was transferred to the Coast Guard with whom she served until 24 November 1930. Fanning was sold for scrap 2 May 1934.