Initially, she served on the Neutrality Patrol, established by President Franklin D. Roosevelt to keep the war in Europe from spreading to the western hemisphere.

The attack on Pearl Harbor and America's entry into World War II found the destroyer in Iceland completing the first leg of one such round-trip voyage.

For Operation Torch, the invasion of Vichy French-controlled North Africa, Woolsey was assigned to Destroyer Squadron 13 (DesRon 13) which served as antisubmarine screen for the Center Attack Group, the Fedhala landing force.

After a meandering and mercifully uneventful crossing, the ships reached the vicinity of the Moroccan coast, and each of the three task groups went their separate ways.

Resistance soon dissipated, and Woolsey seems not to have participated actively in this phase of the operation other than to conduct antisubmarine patrols against a menace which, at that juncture, failed to materialize.

Woolsey, still on antisubmarine patrol, at noon off the harbor mouth caught the submarine's reflection with her sonar and, joined by Swanson and Quick, charged to the attack.

After a series of training operations along the eastern seaboard primarily off the New England coast the destroyer began duty escorting transatlantic convoys in mid-January 1943.

The warship then plied the waters of the eastern seaboard until mid-May, conducting antisubmarine patrols and screening coastwise convoys between Norfolk and New York.

On 15 June, she departed Morocco, but, instead of returning to the United States as she had done in the past, she headed via Gibraltar to Algiers on the Mediterranean coast of North Africa.

Save for one brief round-trip voyage to Algiers in mid-July, Woolsey provided gunfire support for the troops operating ashore on Sicily and helped to defend Allied shipping from German air attacks.

That event occurred just after 16:30 when her shore fire control party called upon her to join Bristol in shooting up an enemy tank formation.

Late in January 1944, the destroyer returned to amphibious operations, this time as a unit of the Fire Support Group for the Anzio landings.

Completing her repairs at Boston in mid-March, she conducted refresher training at Casco Bay, Maine, before heading back to the Mediterranean at the end of the third week in April.

While operating with a hunting group composed of Benson, Ludlow, and Niblack in mid-May, Woolsey experienced her third and last encounter with a German U-boat.

A report of torpedo tracks from a newcomer to the Mediterranean, U-960, brought DesDiv 25 to the area between Oran and Cartagena early on 17 May to commence a two-day search and destroy mission.

Immediately, all five destroyers opened fire on the submarine while a British Wellington bomber dropped depth bombs from a low altitude near U-960.

Following that action, Woolsey continued relatively routine patrols until the end of July when she began preparations for the invasion of southern France.

After operating along the New England coast until late April and escorting a convoy to Great Britain in May, the warship returned home to receive a reinforced antiaircraft battery preparatory to her impending transfer to the war in the Pacific.

After stops at Pearl Harbor and San Diego, the destroyer ended her brief interlude with the Pacific Fleet on 29 November when she retransited the Panama Canal.