After the United States entered World War I in April 1917, Winslow was sent overseas to patrol the Irish Sea out of Queenstown, Ireland.

Four oil-burning White-Forster boilers powered the engines, which could generate 17,000 shp (13,000 kW), moving the ship at up to 29 knots (33 mph; 54 km/h).

The General Board of the United States Navy had called for two anti-aircraft guns for the O'Brien-class ships, as well as provisions for laying up to 36 floating mines.

After trials off the upper east coast, Winslow joined the 6th Division, Atlantic Fleet Torpedo Flotilla.

The destroyer participated in maneuvers in Cuban waters during the winter of 1915 and 1916 and, in the spring, began operations along the eastern seaboard.

At 0530 on 8 October 1916, wireless reports came in of a German submarine stopping ships near the Lightship Nantucket, off the eastern end of Long Island.

After an SOS from the British steamer West Point was received at about 1230, Rear Admiral Albert Gleaves ordered Winslow and other destroyers at Newport to attend to survivors.

She had been there guarding the river mouth since February when American relations with Germany began to deteriorate as a result of the latter country's return to unrestricted submarine warfare.

Soon after US Congress declared war, Winslow moved north to the New York Navy Yard to prepare for duty overseas.

[1] On 30 July, Winslow picked up the master and 12 crewmen from SS Whitehall,[1] torpedoed the day before by U-95,[16] and brought them safely into Queenstown.

[1] She sighted another U-boat off Queenstown on 16 August, but heavy weather covered the submarine's tracks when it submerged and Winslow made no attack.

[1] Winslow dropped a depth charge barrage on what appeared to be the submarine's moving wake, but broke off the attack to assist the schooner's crew;[1] all were saved, but Henry Lippitt was sunk.

In neither case did she receive visible confirmation of a sinking; however, during the 3 January attack, one of her depth charges threw a large mass of dark liquid high in the air.

Depth charges dropped by Winslow, Conner, Nicholson, and Wainwright failed to sink the U-boat,[1] but, combined with defensive efforts from Mount Vernon herself, helped prevent the submarine from launching a coup de grâce against the former German liner.

When President Woodrow Wilson arrived at Brest on George Washington on 13 December, the destroyer served as part of that transport's escort into the harbor.

After that, the destroyer returned to normal operations along the east coast and annual winter maneuvers in Cuban waters until placed in reduced commission at Philadelphia on 10 December 1919.