During February and March 1914, Benham conducted a shakedown cruise to the West Indies and, in April, began operations out of Hampton Roads, Virginia. In July, the destroyer went into reserve at the New York Navy Yard. She came back into active service on 21 December 1914 and plied the waters along the East Coast until the United States entered World War I in the spring of 1917. During that time, in October 1916, Benham rescued the crew of the Dutch steamer SS Blommersdijk which had been torpedoed by U-53 off the New England coast.
After the United States entered World War I on 6 April 1917, Benham was one of the first group of destroyers chosen for antisubmarine duty in European waters. She departed Tompkinsville, New York on 17 May and arrived in Queenstown, Ireland, on 24 May. Four days later, the destroyer began the first of many tours of duty at sea hunting U-boats and shepherding convoys to their destinations.
Her first encounter with U-boats came on 13 July when she was apparently attacked by two submarines. They launched a total of three torpedoes at Benham, but she and her convoy evaded them. The destroyer then drove them away with a depth charge attack.
On 30 July, while she was on her way to Queenstown, the destroyer spied the wake of another torpedo some 1,500 yards from her. Immediately, she charged to the attack with guns and depth charges. Later, her crew sighted air bubbles and oil on the surface. The British Admiralty commended her for probable damage to a German U-boat. The destroyer continued her patrols out of Queenstown until June of 1918 when she moved to Brest, France, her base of operations through the end of World War I.
On 21 December 1918, Benham put to sea from Brest for the last time and began the voyage back to the United States. Rejoining the Atlantic Fleet at the beginning of 1919, the warship participated in the annual fleet maneuvers held in Cuban waters and then made a cruise to the Azores in May. Upon her return that summer, she was placed in ordinary at Norfolk on 28 June. Active again in 1921, she cruised the eastern seaboard until assigned duty as plane guard and tender to the Atlantic Fleet Air Squadrons. That duty terminated in May 1922, and she stood into Philadelphia on the 12th to prepare for inactivation.
Benham was placed out of commission there on 7 July 1922. Her name was struck from the Naval Vessel Register on 8 March 1935 and, after she had been scrapped by the Philadelphia Navy Yard, her materials were sold on 23 April 1935.