She was launched on 20 October 1921, sponsored by Miss Mary Howe, and commissioned on 14 July 1923 with Lieutenant Wilder D. Baker in command.

Departing New London, Connecticut, on 24 November 1924, she proceeded, via the Panama Canal and California, to Hawaii, which she visitied from 27 April to 25 May 1925.

Following voyages to Bermuda, S-13 operated in the Panama Canal area from December 1941 (during which the United States entered World War II with the Japanese attack on Pearl Harbor on 7 December) to June 1942; off Guantanamo Bay, Cuba, from June to August 1942; and in the Panama Canal area beginning in August 1942.

S-13 was decommissioned on 10 April 1945, struck from the Naval Vessel Register on 19 May 1945. and sold on 28 October 1945 to Rosoff Brothers of New York City for scrap.

The 1930 John Ford film Men Without Women is set aboard a fictional U.S. Navy submarine named USS S-13.