Lansdale escorted seven troopships from New York City to Key West from 22 to 27 January 1942 before arriving Casco Bay, Maine on 1 February to serve as plane guard for the aircraft carrier Wasp.

For the next six months, anti-submarine warfare 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 the light cruisers Savannah and Juneau, after which she resumed convoy screening out of Norfolk, Virginia.

As the convoy steamed south of the Azores on the 23rd, a German wolf pack of six to 10 submarines made early morning and late night attacks that sank three tankers and damaged two others.

Continuing escort duty out of Norfolk, Virginia, Lansdale made a run to Casablanca and back from 3 November to 17 December before sailing again for north Africa on 13 January 1944.

After escorting the light cruiser Brooklyn to Algiers, she arrived Pozzuoli, Italy on 14 February for operations off the Anzio beachhead.

Until returning to Oran from 22 to 26 March, she searched for German submarines and screened the light cruiser Philadelphia during fire support and shore bombardment operations from Naples to Anzio.

Lansdale departed Oran on 10 April and joined convoy UGS 37, composed of 60 merchant ships and six LSTs, bound from Norfolk to Bizerte.

Although the destroyer escort Holder took a torpedo hit amidships, warning of an impending attack, an effective smokescreen, and massive, accurate anti-aircraft fire repulsed the enemy planes.

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.

Attacking as twilight faded on 20 April, the German planes, flying close to shore and low over the water, evaded radar detection until they were almost upon the convoy.

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.

Lt. William B. Neal Jr. was cited for distinguished heroism following the attack, receiving the Navy and Marine Corps Medal, Although injured, he continued to provide first aid after the order to abandon ship was given.