In San Francisco when the Japanese made their surprise Attack on Pearl Harbor, Kaskaskia immediately began preparations to join the Service Force in the Pacific.

As the Navy pushed relentlessly toward Japan, Kaskaskia departed Pearl Harbor 16 January 1944 to support operations in the Marshall Islands.

Throughout June and July Kaskaskia remained on hand, assisting the fleet to take Saipee, Guam, and Tinian – important supply areas in the future campaign for the Philippines.

As the Navy fought toward the Philippines, the decision was taken to assault the Palau Islands as a staging area for aircraft and ships during the invasion of Leyte.

She departed Ulithi 3 July to refuel units of the carrier task forces, launching raids on the Japanese Islands of Honshū and Hokkaidō.

She continued refueling operations in Japan, China, and Formosa for an entire year before arriving San Pedro 28 September 1946.

When North Korean troops invaded South Korea, the United States accepted the challenge and ordered its forces to defend the embattled peninsula.

Kaskaskia was transferred to Military Sealift Command 8 January 1957, and operated in that capacity with a Navy crew until 21 October 1957 when she decommissioned and was turned over to the Maritime Administration 10 December.

Throughout the summer she engaged in exercises off the Florida Coast, and sailed to the Azores to participate in Project Mercury, manned orbital flights.

She was in company with the aircraft carrier USS Kearsarge during the latter's recovery of Astronaut Walter Schirra 3 October, demonstrating the large role of the Navy in space operations.

President John F. Kennedy ordered the blockade when the Soviet Union tried to plant offensive missiles only 90 miles (140 km) from the United States.

During 1964 Kaskaskia engaged in fueling operations and exercises off Florida and in the Caribbean, constantly seeking improved methods to increase the mobility of the Fleet.

Highlights of this period were service to ships patrolling off the coast of riot-torn Santo Domingo in the summer of 1965, and participation in the recovery team for an unmanned Apollo Program space flight in February 1966.