After completion at the Boston Navy Yard, R-5 got underway on 28 April 1919 for New London, Connecticut, where she was assigned to Submarine Division 9 of the Atlantic Fleet.

In company with Camden (AS-6), R-5 was ordered to the Pacific Ocean on 11 April 1921, transited the Panama Canal on 28 May, and arrived on 30 June at her new base, San Pedro, California.

In January 1923 she was used in the filming of the Twentieth Century-Fox motion picture The Eleventh Hour, and engaged in war games with the battle fleet in the Gulf of Fonseca from 5 February to 6 April 1923.

She was transferred on 16 July along with Division 9 to Pearl Harbor where she was based for the next eight years engaged in training and operations with fleet units.

R-5 made an endurance run to Midway Island in July and August 1924 and in December, during division exercises off Pearl Harbor, rammed R-16 (SS-93) in the after battery room, causing extensive damage to both ships.