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

In October 1917, Nicholson steamed to the rescue of J. L. Luckenbach, driving off German submarine U-62, which had shelled the American cargo ship for over three hours.

In September 1918, Nicholson helped drive off U-82 after that U-boat had torpedoed the American troopship Mount Vernon off the coast of France.

Construction of the vessel was awarded to William Cramp & Sons of Philadelphia which laid down her keel on 8 September 1913, the same date as of sister ship O'Brien.

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 kn (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.

[16][Note 2] Nicholson trained her 4 in (100 mm) guns on the U-boat and, by the time her gunners had fired a second round, U-62 submerged and disappeared.

The periscope belonged to U-58 under the command of Kapitänleutnant Gustav Amberger,[19] who was lining up a torpedo shot on the British steamer SS Welshman.

These three knocked out all electrical power and the manual diving plane controls, which caused the submarine to descend through a depth of 164 ft (50 m).

In early September 1918, Nicholson was one of six destroyers escorting a westbound pair of US Navy transports, Agamemnon and Mount Vernon.

[23][24] On the morning of 5 September, about 250 nmi (290 mi; 460 km) west of Brest,[24] German submarine U-82 torpedoed Mount Vernon, knocking out half of the troopship's boilers.

[25] Nicholson, Conner, Winslow, and Wainwright, all depth charged the U-boat without success,[23] but, combined with defensive efforts from Mount Vernon herself, helped prevent the submarine from launching a coup de grâce against the former German liner.

After arriving at New York on 10 January 1919, Nicholson resumed operations along the east coast until placed in reserve at Philadelphia on 27 November.