With war raging in Europe and tension increasing in the pacific, Drayton joined in the constant exercises and tactical problems preparing the fleet for action.

After screening a tanker to Suva Harbor, Fiji Islands, Drayton sailed for the United States 25 March and arrived at San Pedro, Los Angeles, 5 April.

She sortied from Espiritu Santo 29 November with TF 67 to intercept a Japanese naval force guarding transports en route to reinforce Guadalcanal.

She screened high-speed transports from Buna Roads to the invasion of Saidor 2 January, and aside from a brief voyage to Sydney to replenish, remained on patrol and escort duty for the occupation of the Bismarck Archipelago.

She returned with reinforcement troops from Milne Bay 4 March and began operating as headquarters for the Landing Craft Control Officer for the Admiralties.

Drayton bombarded Pityilu Island 12 March then sailed for Seeadler Harbor, Manus, escorting an LST convoy before returning to New Guinea.

On 6 December while screening a convoy of LCMs and LCIs to San Pedro Bay, Drayton was attacked by a twin-engine bomber which scored a near miss, killing two and wounding seven of the destroyer's crew.

Drayton extinguished her fires and carried out her mission, convoying her charges safely to harbor and then sailing unassisted to Manus, New Guinea for repairs.

From 27 January to 18 February, she served on patrol and gave fire support, bombarding enemy troops in the foothills and destroying a strong point in a cave.