Following outfitting and trials, S-3 began her career with training operations along the New England coast operating out of Portsmouth and New London, Connecticut. In 1920, she twice visited Havana, Cuba: first in January, and again in December.
In July 1921, she was attached to Submarine Division 12 (SubDiv 12) which, along with SubDiv 18, was to rendezvous off Portsmouth for the longest voyage on record, at that time, for American submarines. The two divisions were assigned to the Asiatic Fleet as Submarine Flotilla 3 (SubFlot 3) at the Cavite Naval Station in the Philippine Islands. They sailed via the Panama Canal to Pearl Harbor, where S-3 was detached and reassigned to operate on the West Coast of the United States from Mare Island, California. The two divisions continued on and successfully completed the voyage, arriving at Cavite on 1 December.
S-3 departed Pearl Harbor on 9 November and sailed to the U.S. West Coast where she operated until mid-July 1923. On 17 July, she took departure from San Francisco Bay to retransit the Panama Canal en route to New London.
Reaching New London on 5 September, she was attached to SubDiv 2, Atlantic Fleet, and assigned experimental duty at the Submarine School at New London, assuming the duties of S-1, flagship of SubDiv 2, which was conducting special experiments with aircraft. During the remainder of 1923 and the years following, into 1927, she ranged the East Coast of the United States conducting training operations and evaluating new techniques in submarine development.
In July 1927, S-3 and S-1 formed SubDiv 4 and began a schedule which included operational cruises to the Panama Canal Zone in the spring months of 1928–1930. The remaining months of those years were spent in operations along the New England coast.
