Case was berthed at Pearl Harbor when the Japanese struck on 7 December 1941, then served in the United States Pacific Fleet until the end of World War II.

Returning to Pearl Harbor in late November 1942, Case cleared to escort a convoy to the Fiji Islands, arriving 20 December.

From Fiji she sailed to Guadalcanal to screen a convoy during its unloading period, and on 1 January 1943, arrived at Espiritu Santo, her base for escort, patrol, and training duty through 23 September.

Palau and the western Carolines were the targets 30 March-1 April, and Case next sailed from Majuro for the late-April air raids on Hollandia, Truk, Satawan, and Ponape.

A month of local screening and escort duty at Majuro preceded Case's assignment to TG 58.4 for the strikes on Japanese airfields in the Bonins, designed to neutralize these bases during the invasion of the Marianas.

After a repair period at Eniwetok, Case resumed her operations with TG 58.4, screening for air strikes preparing for the landings on Guam late in July 1944, and the attacks on the Bonins on 4 and 5 August.

Resuming escort duty from Ulithi, Case was screening cruisers bound for Saipan on 20 November, when she rammed and sank a Japanese midget submarine at the entrance to Mugai Channel.

[1] At 19:51, she sighted a submarine on the surface in the Philippine Sea 425 nautical miles (787 km; 489 mi) southeast of Kagoshima, Kyushu, Japan at 29°14′N 137°18′E / 29.233°N 137.300°E / 29.233; 137.300 which did not respond to recognition signals.