After shakedown between Newport and Hampton Roads, she was assigned to Division Five, Torpedo Flotilla, Atlantic Fleet in December 1915. From early 1916 through the spring of 1917 she operated with the Fleet along the East Coast and in Cuban waters.
Returning from winter maneuvers off Cuba in March 1917, the ship was lying in Virginia’s York River when the United States entered World War I on 6 April. After fitting out at Brooklyn Navy Yard, she got underway from New York on 15 May and joined a convoy at Halifax, Nova Scotia, en route to Ireland. Upon arrival at Queenstown on 24 May, she was assigned to Destroyer Division 6, which cooperated with the British Forces. She patrolled off the Irish coast in company with other destroyers answering distress calls and meeting eastbound convoys to escort them through the war zone.
While escorting SS Elysia 12 miles off Queenstown 16 June 1917, O’Brien sighted a periscope. Heading toward the submarine for an attack, a lookout in the foretop saw the submerged boat pass close along the starboard side. A depth charge was dropped but no immediate evidence of damage was found. Nearly three hours later, the British vessel Jessamine reported a large patch of oil in approximately the same position. The next morning Cushing also reported and confirmed Jessamine’s report. The British Admiralty believed the submarine was probably seriously damaged. However, later investigation has shown that the contact, German submarine U-16, continued to operate and completed her cruise.
In the summer of 1918, O’Brien was transferred to the French coast where she continued her antisubmarine patrol.
After the Armistice, she transported mail and passengers between Brest, France, and Plymouth, England. She returned to New York on 8 January 1919, and decommissioned in Philadelphia 9 June 1922. O’Brien was struck from the Navy List on 8 March 1935. She was scrapped at Philadelphia Navy Yard and her materials were sold on 23 April.