Lansdowne first operated along the Atlantic seaboard on shakedown, antisubmarine, and escort duty, and attacked an enemy submarine off Cape Hatteras on 3 July.

Arriving Nukuʻalofa Bay on 6 September, the destroyer joined Task Force 18 (TF 18), under Rear Admiral Leigh Noyes aboard the aircraft carrier Wasp.

The first torpedo was fired at a range of 1,000 yards (910 m) and set to run 15 feet (4.6 m) under Wasp's keel for maximum damage with the magnetic influence exploder.

[3] Lansdowne, with Task Group 64.1 (TG 64.1), took part in the occupation of Funafuti, Ellice Islands, 2 October, then escorted aircraft ferry Hammondsport to Espiritu Santo.

On 30 November, Lansdowne made three attacks against a submerged target west of Koli Point, bringing diesel oil, slabs of cork, and air bubbling to the surface.

She headed back to Espiritu Santo from Pearl Harbor 30 July, and joined an antishipping force off Vella Lavella on 2 September.

While covering landing operations at Empress Augusta Bay 28 November, the ship repelled an enemy air attack and, two days later, bombarded Bougainville, which she hit again late in December.

During January and February 1944, Lansdowne covered the landings at Torokina, Bougainville, and Green Island, and conducted antishipping sweeps between Buka and Rabaul.

After operating northwest of the Admiralties, Lansdowne joined TFs 77 and 78 for the initial landings in the Aitape–Hollandia–Tanahmerah area of northern New Guinea and launched air attacks on Palau, Yap, Ulithi, and other enemy bases in the Central Pacific on 3 March through 1 April.

Lansdowne next operated with the 3rd Fleet off Japan screening logistics groups and fast carriers launching strikes against the enemy homeland.

She operated out of Yokohama until sailing on 15 October from Wakanoura for the United States via Singapore, Colombo, and Cape Town, arriving at the Brooklyn Navy Yard on 6 December 1945.