She was launched on 10 September 1919 by the Bethlehem Shipbuilding Corporation, Squantum, Massachusetts; sponsored by Mrs. R. C. Walling; and commissioned on 4 December 1919 at the Boston Navy Yard.

As a unit of the 43d Division, 1st Squadron, Destroyer Force, Atlantic Fleet, Isherwood conducted shakedown out of Boston until 26 January 1920 when she sailed for Cuba via Newport, Rhode Island.

Arriving Guantanamo Bay 3 February she remained there engaging in target practice and drills until departing 26 April, escorting the battleship Pennsylvania to receive the Secretary of the Navy at Lynnhaven Roads, Virginia.

Following repairs at the Boston Navy Yard (13 March – 8 May 1922), Isherwood joined Destroyer Squadron 9 at Philadelphia and proceeded to Yorktown, Virginia, for exercises with the Fleet.

From Jacksonville, Florida, she received Naval Reservists for a summer cruise (Maine to Massachusetts) 29 June, and following their disembarkation 20 July, she underwent repairs at Newport and overhaul at Norfolk.