After shakedown in the Caribbean, Lansdale departed Boston 18 January 1941 for neutrality patrol duty in the Caribbean. She cruised off Cuba, the Virgin Islands, Martinique, and the British West Indies before returning to Boston 6 March. After escort training along the Atlantic coast, she screened transports from Charleston, S.C., to Argentia, Newfoundland, in late June, then departed Argentia 30 June on a neutrality-patrol run to Iceland. During the remainder of the year she made three escort runs between Newfoundland and Iceland. En route to Hvalfjordur, Iceland, when the United States entered the war against the Axis, she steamed to Boston 15 to 24 December.

Lansdale escorted seven troopships from New York to Key West. 22 to 27 January 1942 before arriving Casco Bay, Maine, 1 February to serve as plane guard for Wasp (CV 7). For the next 6 months ASW patrols and escort run carried her from the eastern seaboard to Iceland, the Caribbean, the Panama Canal, and the Gulf of Mexico. From 8 to 21 May she patrolled the Atlantic between Puerto Rico and Bermuda with Savannah (CL-42) and Juneau (CL-52), after which she resumed convoy screening out of Norfolk.

On 9 August Lansdale joined a convoy out of Halifax, Nova Scotia, bound for northern Ireland. Arriving Lisahally the 18th, she returned as escort from Greenock, Scotland, to New York 27 August to 5 September. After escorting another convoy from New York via Halifax to northern Ireland, she returned to New York 10 to 21 October as screen for Arkansas (BB-33), then departed 2 November with Task Force 38 to escort convoy UGF-2 to north Africa. Arriving Safi, French Morocco, 18 November, she patrolled approaches to Safi and Casablanca until 22 December when she sailed for New York in a convoy of 41 transports and six escorts.

Reaching New York 10 January 1943, she underwent overhaul until 30 January when she departed with a convoy for northern Ireland. She reached Londonderry 9 February, joined with units of the 42d British Escort Group, and departed 15 February to escort tankers from the United Kingdom to the West Indies. As the convoy steamed south of the Azores on the 23d, a German wolf pack of 6 to 10 submarines made early morning and late night attacks that sank three tankers and damaged two others. Lansdale made several ASW counterattacks without known results but two nights later she hit a submerging U-boat with 5-inch gunfire. Although scattered night attacks continued until the 27th, prompt, aggressive counterattacks by American escorts prevented further losses.

Lansdale arrived Port-au-Spain, Trinidad, 6 March as escort for SS Maasyerk before proceeding 8 to 9 March to Curaçao, Netherland West Indies, for more escort duty. From 20 March until 6 October she made eight escort runs between the Caribbean and the United Kingdom, three convoy runs between Curaçao and New York, and periodic escort and patrol runs to Puerto Rico and the Virgin Islands.

Continuing escort duty out of Norfolk, Lansdale made a run to Casablanca and back between 3 November and 17 December before sailing again for north Africa 13 January 1944. She reached Casablanca 1 February and continued the next day via Oran and Algiers to Tunis where she arrived the 10th. After escorting Brooklyn (CL-40) to Algiers, she arrived Pozzouli, Italy, 14 February for operations off the Anzio beachhead. Until returning to Oran 22 to 26 March, she searched for German submarines and screened Philadelphia (CL-41) during fire support and shore bombardment operations from Naples to Anzio.

Lansdale departed Oran 10 April and joined convoy UGS-37, composed of 60 merchant ships and six LSTs, bound from Norfolk to Bizerte. At 2330 on 11 April some 16 to 25 German Dornier and Junkers bombers attacked the convoy off Cape Bengut, Algeria. During the next hour the planes lit the night with flares and struck at the tightly formed convoy with torpedoes and radio-controlled bombs. Although Holder (DE-401) took a torpedo hit amidships, warning of an impending attack, an effective smokescreen, and massive, accurate antiaircraft fire repulsed the enemy planes. While losing four planes, the Germans failed to sink a single ship.

Leaving UGC-37 on 12 April, Lansdale escorted three merchant ships from Oran to westbound convoy UGS-36. Then she sailed from Oran 18 April to join UGS-38 the next day. Stationed off the port bow of the Bizerte-bound convoy, she served as a “jam ship” against radio-controlled bombs, in addition to screening against U-boats. As the ships hugged the Algerian coast during first watch 20 April, they approached approximately the same position off Cape Bengut where the Luftwaffe had attacked UGS-37 on 11 to 12 April. Though warned of possible attack during the afternoon and evening, the ships had little chance to avoid the strike unleashed by the Germans shortly after 2100.

Attacking as twilight faded, the enemy planes, flying close to shore and low over the water, evaded radar detection until they were almost upon the convoy. Some 18 to 24 Junkers and Heinkel bombers struck in three waves, minutes after Joseph E. Campbell (DE-70) of the outer screen reported, “they are all around me . . . they are enemy, they are enemy.”

The first wave of about nine JU-88s attacked from dead ahead. Their torpedoes damaged SS Samite and detonated high explosives on board SS Paul Hamilton, blowing her out of the water and killing all 580 men on board. The second wave of about seven Junkers hit the starboard flank of the convoy and damaged two more merchant ships, one fatally. And the third, consisting of about five HE-111s, bore down on the convoy’s port bow, Lansdale’s station.

Silhouetted by the explosion of Paul Hamilton at 2104, Lansdale was attacked from both port and starboard by planes from two and possibly three waves. As Heinkels approached on the port bow and launched two torpedoes that missed, Lansdale turned to starboard to repel five JU-88s which had veered seaward from the convoy. Her guns hit one as it passed down the starboard side; but, as it splashed well astern, another launched a torpedo 500 yards on the starboard beam before passing over the forecastle under heavy fire and splashing on the port quarter.

The torpedo struck the starboard side forward about 2106, wrecking the forward fireroom and opening both sides to the sea. Almost split in two, Lansdale immediately took a 12° list to port. Her rudder jammed 22° right, and she steamed at 13 knots in a clockwise circle.

At 2112 she again came under attack. Two bombers launched torpedoes on the beam and broad on the bow to port but both missed the still-turning ship. Despite the increasing list, her guns splashed one of the planes as it turned away from the ship.

At 2120 the course of the ship straightened out, but the list increased steadily. Within 2 minutes it reached 45° despite the valiant efforts of her crew to control the battle damage. Her skipper, Lt. Comdr. D. M. Swift, ordered her abandoned when he feared the stricken ship might roll “completely over.” By 2130 the list had increased to 80° and the destroyer began to break up. Five minutes later she broke in half, and the stern section quickly sank. The forward section sank 20 minutes later as Menges (DE-320) and Newell (DE-322) began rescue operations.

The two destroyer escorts swept the water from 2155 until 0330 the next morning searching for survivors. Menges picked up 115 men, including two German fliers who were shot down either by Lansdale or Newell. Newell rescued 119 survivors, including Lieutenant Commander Swift. Forty-seven officers and men were carried down with Lansdale.

Lansdale earned four service stars during World War II.