Still outfitting when the United States entered World War II, Ellyson was quickly readied for sea and patrolled in the Atlantic, protecting Allied shipping from Halifax, Nova Scotia, to the West Indies and Panama Canal.

In August 1942 Ellyson began operating with the aircraft carrier Ranger, and remained with her through the landings at Fedhala, French Morocco, on 8 November.

After two months of escort duty along the east coast, she rejoined Ranger on two voyages to Casablanca to ferry Army planes to north Africa.

She sailed for England on 12 May in the screen of the battleships South Dakota and Alabama, and operated with the British Home Fleet out of Scapa Flow in the Orkney Islands screening convoys, giving distant support to Allied shipping to Murmansk and Iceland, and attempting to lure German battleship Tirpitz and other German surface ships from the safety of Norwegian bases to battle on the open seas.

Later, moving into the battleship's screen, Ellyson touched Bahia, Brazil; Freetown, Sierra Leone, Dakar, and Port Royal, South Carolina; before returning to Boston, Massachusetts, on 19 December.

On 25 June she saw action off Cherbourg, blasting gun installations, destroying naval mines, and laying a smoke screen for larger fleet units.

Ellyson remained on patrol to cover the landing of reinforcements and support the invasion until October, then sailed for Boston, arriving 8 November to begin conversion to a high-speed minesweeper.

The varied and dangerous duties assigned her squadron in the Okinawa operation took a heavy toll, only three of the 12 ships with whom she sailed in the next three months survived undamaged.

Flames and the threat of a magazine explosion forced Ellyson to sink the stricken destroyer early on 7 April to prevent her drifting on to Japanese-held Ie Shima.

Attached to Mine Force, Atlantic Fleet, Ellyson continued to operate from Charleston on training duty along the east coast and in the Caribbean.