R-4 deployed to the Pacific Ocean on 11 April 1921, transited the Panama Canal on 28 May, and arrived at her new base, San Pedro, California, on 30 June.

R-4 was transferred on 16 July with Division 9 and Canopus (AS-9) to Pearl Harbor where she remained for the next eight years engaged in training and operations with fleet units.

On 12 September 1925 R-4 rescued John Rodgers and his crew, who had just failed to make the first aerial crossing of the Pacific from California to Hawaii, off the coast of Kauai.

She was soon assigned to Division 4 and served as a training ship for the next ten years on rotating duty between the New London Submarine School and the Yale University NROTC unit.

Back at New London for the first two weeks in July, she returned to Key West at midmonth and until March 1945 alternated duties for the Fleet Sonar School with patrols in the Florida Strait and the Yucatán Channel.