Following shakedown and practice amphibious assault training on the U.S. West Coast, President Jackson sailed for the South Pacific 1 July 1942, as a unit of Transport Division 2. She landed the 1st Battalion, 2nd Marines, on Florida Island, Solomon Islands, 7 August 1942. At mid-month she evacuated 500 survivors of the "First Battle of Savo Island" to Noumea, then began bringing in reinforcements and evacuating casualties of land and sea actions.
Redesignated APA–18 on 1 February 1943, President Jackson continued to transport reinforcement troops and cargo in support of the consolidation of the southern Solomons. On 30 June, she landed the 172nd U.S. Army Combat Team and two construction battalion companies on Rendova, then transported survivors of USS McCawley (AP-10), torpedoed by a submarine, to Noumea.
Operating with other vessels of task force TF 31, President Jackson landed elements of the 3rd Marine Division at Empress Augusta Bay, Bougainville Island, 1 November. Seven days later, while en route back to that island with reinforcements, she was hit by a 550-pound (250 kg) bomb, which fortunately did not explode.
On 25 March 1944 President Jackson landed army, navy, and units on Emirau Island and in April, with Transport Division Two, she carried the 40th Division, to New Britain, and returned the 1st Marine Division to Russell Islands in the Solomons. With task force TF 53, in July, she landed elements of the 3rd Marine Division on Guam, 21 July, then evacuated casualties to Pearl Harbor and the United States. On 23 October the ship returned to duty with Transport Division 32 in the south and southwest Pacific areas.
While operating with TF 77, President Jackson landed elements of the 25th Infantry Division, U.S. Army, in the reinforcement landing at Lingayen Gulf 11 January 1945. On 21 February, while operating with TF 51, she landed elements of the 3rd Marine Division on Iwo Jima. Exposed to enemy counter-battery fire, she was hit once in a barrage of 37mm fire with minor damage and casualties. On 6 March she departed Iwo Jima with 515 casualties for Saipan and Noumea.
With army and navy casualties and miscellaneous passengers aboard, the transport sailed for the United States 7 May 1945. She got underway from San Francisco, 14 June and completed two round-trips to Manila before the cessation of hostilities which found her in drydock at Seattle, Washington. She then entered upon "Operation Magic Carpet" duty.