Sampson was assigned to Division 9 of the Atlantic Destroyer Force and conducted shakedown training out of Narragansett Bay. After war games off Provincetown, Massachusetts, she cleared Tompkinsville on 15 May 1917 to join the escort screen of a convoy which touched at Halifax and reached Queenstown, Ireland, on 25 May 1917. She reported for duty with the United States Naval Forces operating in European waters and was assigned to convoy escort duty in the approaches to the British Isles, basing her operations from Queenstown. Two British-type depth charge projectors were installed on her stern; and, on 29 May, she commenced escort duty and protected the troop transports and merchant convoys from hostile submarines throughout the remainder of World War I.
On 18 June 1917, Sampson rescued two small boatloads of survivors of the SS English Monarch and the captain and 13 sailors from the torpedoed SS Elele. The next morning, she picked up 17 other survivors of the Elele; and, on the 20th, she landed all at Queenstown. Sampson answered other distress calls before the end of the war, and she made several attacks to drive off submarines reported or seen near her convoys. She steamed from France with the Queenstown division of destroyers on 29 November 1918 and stood out from Brest Harbor on 12 Decemberto escort President Woodrow Wilson on board George Washington into the harbor. Returning to Queenstown on 14 December, she sailed for home on the 26th and arrived at the New York Navy Yard on 7 January 1919.
After repairs in the New York Navy Yard, Sampson was assigned to the 4th Division, 2d Flotilla, of the Destroyer Force and sailed on 22 March 1919 to base her operations from the Naval Torpedo Station at Newport, Rhode Island. She reported to the Inspector of Ordnance for experimental testing of torpedoes and mines, but interrupted this duty in May 1919 to assist in guarding the route of the NC-4 during that Navy seaplane’s crossing over the Atlantic, the world’s first successful trans-oceanic flight. She entered the New York Navy Yard on 1 December 1919 for deactivation overhaul, which was completed on 14 February 1921. Towed to the Philadelphia Navy Yard, Sampson was decommissioned on 15 June 1921. She remained inactive during the years that followed; and, on 17 July 1935, was ordered scrapped in accordance with the London Treaty for the reduction of naval armaments. Her name was struck from the Navy list on 7 January 1936, and she was sold for scrap on 8 September 1936 to Boston Iron and Metal Co., Inc., Baltimore.