After shakedown and training in Casco Bay, Maine, Jeffers operated briefly on the East Coast until departing Norfolk on 18 February 1943 on her first transatlantic voyage escorting a convoy to Casablanca and returning 14 April.

While preparing for the giant assault on Sicily, she patrolled off other African ports, shooting down a German bomber during 6 July Luftwaffe raid on Bizerte.

Jeffers sailed two days later with Rear Admiral John Hall's force for Gela; and, upon arrival 9 July, she guarded the transports.

Early next day the great assault began, with Jeffers assigned the task of shooting out shore searchlights and providing fire support for the Amphibious Battle of Gela.

As the Allies began the great buildup of men and materiel in Britain for the landings in northern France, Jeffers made five voyages between 5 September 1943 and 22 April 1944.

For the next two weeks she convoyed transports from Belfast to Utah Beach as more troops and supplies were poured into the beachhead, finally departing for the Mediterranean on 16 July.

Assigned to screen escort carriers covering the operation, Jeffers departed Malta on 12 August to join her task group.

In February she moved on to Pearl Harbor and from there to the great advance base at Ulithi to prepare for the Okinawa invasion, last and largest amphibious operation of the war against Japan.

As part of the preliminary minesweeping group, Jeffers arrived off Okinawa on 24 March, one week before the landings, and began clearing mines and marking boat lanes.

The veteran ship steamed into Kerama Retto to repair battle damage later that afternoon, emerging on 16 April to join a carrier group operating off Okinawa in support of ground forces.

Departing again on 26 June, Jeffers sailed via Saipan and Ulithi to Kerama Retto, and spent the next six weeks on minesweeping operations north of Okinawa.

Jeffers spent the first half of 1953 in training off the Virginia Capes, departing Norfolk on 16 September for operations with the aircraft carrier Bennington and units of the Royal Canadian Navy in the Mediterranean.