Cassin underwent alterations until March 1937, then cruised to the Caribbean and Brazil. In April 1938, she joined forces at Pearl Harbor for the annual fleet exercises in the Hawaiian Islands and the Panama Canal Zone. During 1939, she operated on the West Coast with torpedo and gunnery schools, and on 1 April 1940 was assigned to the Hawaiian Detachment. Cassin sailed on maneuvers and patrol in the Pacific, cruising from February to April 1941 to Samoa, Australia, and Fiji. Fall of 1941 found her calling at west coast ports.
Cassin was in dry dock with Downes (DD-375) and Pennsylvania (BB-35) at Pearl Harbor on 7 December 1941. In the Japanese attack, an incendiary bomb exploded Downes’ fuel tanks, causing uncontrollable fires on board both Downes and Cassin. Cassin slipped from her keel blocks and rested against Downes. Both ships were considered lost, and Cassin was decommissioned as of 7 December 1941. However, superb salvage saved Cassin, to play an outstanding role in World War II, and she was towed to Mare Island Navy Yard for rebuilding.
Recommissioned 6 February 1944, Cassin reported at Pearl Harbor 22 April, and was assigned escort duty from Majuro until August. By shooting out caves and bombarding Aguijan Island, she aided in the consolidation of Tinian from 15 to 25 August, and then assumed escort duties out of Saipan.
Her guns took revenge on the Japanese once more when she took part in the bombardment of Marcus Island on 9 October. This was part of the preparations for the Leyte assault, and was an attempt to convince the Japanese that the main attack they sensed was coming would be directed at the Bonins. With the same force that had struck at Marcus, Cassin sailed on to join TG 38.1 on 16 October, as the carriers of that group prepared the air strikes designed to neutralize the Japanese airfields in the Manila area prior to the assault landings on Leyte. Cassin steamed northeast of Luzon during the Leyte landings, and when the landings had been successfully launched, was dispatched with her group to refuel and replenish at Ulithi. However, when TF 38 made contact with the Japanese Center Force rounding the southern cape of Mindoro bound for its part in the decisive Battle for Leyte Gulf, Cassin‘s group was recalled to join the approaching action. In the afternoon of 26 October, her group at last reached position to launch aircraft, which attacked the Japanese ships in one of the longest-range carrier strikes of the war. These strikes continued as the Japanese fleet retired north, diminished and battered.
Cassin’s next assignment was to the preparations for the assault on Iwo Jima on the night of 11–12 November 1944, and again on 24 January 1945, she bombarded the island as part of the pre assault softening up and otherwise engaged in patrol, escort and radar picket duties around Saipan. On 23 February, she sailed from Saipan to escort an ammunition ship to newly invaded Iwo Jima, returning to Guam 28 February with a hospital ship laden with some of the many men wounded on the fiercely contested island. She returned to Iwo Jima in mid-March for radar picket and air-sea rescue duty. With periods at Guam and Saipan for replenishment and repairs, she continued on this duty through most of the remainder of the war.
As vivid proof that hazards of war come not only from the enemy, Cassin endured the violence of a typhoon on 6 June 1945, losing one of her men overboard, as well as a motor whaleboat. On 20 July, she bombarded Kita, Iwo Jima, and on 7 August, she boarded and searched a Japanese hospital ship to insure compliance with international law. Since there were no violations, she allowed the Japanese ship to proceed on its way. With the war over, she continued air-sea rescue off Iwo Jima, guarding the air evacuation of released prisoners of war from Japan. She returned to Norfolk, Va., 1 November 1945, and was decommissioned there 17 December 1945. Cassin was sold 25 November 1947.
Cassin received six battle stars for World War II.