The third Casco (AVP-12) was launched 15 November 1941 by Puget Sound Navy Yard sponsored by Mrs. W. J. Giles; and commissioned 27 December 1941, Commander T. S. Combs in command.

After a period patrolling and caring for seaplanes off the northwest coast, Casco arrived at Sitka, Alaska, 5 May 1942 for duty surveying Aleutian waters, laying moorings for seaplanes, and providing tender services. Based at Cold Bay, she operated to Dutch Harbor Chernofaki Harbor, Kodiak, and Nazan Bay. While lying at anchor in the latter on 30 August, she was torpedoed by RO-6l. The resulting explosion killed five of her men, and wounded 20, but prompt and clearheaded action brought flooding to a halt and got the ship underway so that she could be beached and later salvaged. Casco was floated on 12 September, and after emergency repairs at Dutch Harbor and Kodiak, she received a thorough overhaul at Puget Sound Navy Yard.

Casco returned to fog-bound Aleutian duty in March 1943, operating at Constantine Harbor, Amchitka, as tender to Fleet Air Wing Four. In May she steamed to Attu, to care for the seaplanes conducting antisubmarine patrol and search missions in support of the Army's invasion of Attu. Here she remained providing the essential base for flights which guarded against further Japanese reinforcement or penetration of the Aleutians. The tender's service in these waters where weather was often as formidable an enemy as the Japanese ended in November, when she sailed for overhaul at Bremerton, Wash.

Casco arrived in the Marshall Islands in February 1944 to tend seaplanes of patrol squadrons at Majuro and Kwajalein during their occupation, and later at Eniwetok until September. Temporarily assigned to carry cargo in the buildup for the Philippine operations, she shuttled between Saipan, Ulithi, and the Palaus until November, then returned to tender duty, in the Palaus until January 45, and at Ulithi until April. After overhaul at Saipan, she arrived in Kerama Retto 25 April to care not only for seaplanes, but also for a motor torpedo boat squadron, all engaged in the Okinawa invasion and occupation.

Returning to the west coast in July 1945, Casco sailed back to the Far East in the spring of 1946 for operations in the Philippines, then served in training duty off Galveston, Tex. She was decommissioned 10 April 1947, and transferred to the Coast Guard on 19 April 1949.

Casco received three battle stars for World War II service.