|Builder||Lake Torpedo Boat Company|
|Laid down||19 March 1918|
|Launched||23 December 1919|
|Commissioned||17 December 1920|
|Decommissioned||4 October 1944|
|Fate||Sunk as a target, 3 April 1945|
|Class and type||S-class submarine|
|Length||231 ft (70 m)|
|Beam||21 ft 10 in (6.65 m)|
|Draft||13 ft 1 in (3.99 m)|
|Complement||38 officers and men|
|Armament||1 × 4 in (100 mm)/50 deck gun, 4 × 21 inch (533 mm) torpedo tubes|
USS S-16 (SS-121) was a second-group (S-3 or "Government") S-class submarine of the United States Navy. Her keel was laid down on 19 March 1918 by the Lake Torpedo Boat Company in Bridgeport, Connecticut. She was launched on 23 December 1919 sponsored by Mrs. Archibald W. McNeil, and commissioned on 17 December 1920, Lieutenant Commander Andrew C. Bennett in command.
Departing from New London, Connecticut on 31 May 1921, S-16 was attached to Submarine Division 18 (SubDiv 18) and proceeded via the Panama Canal, California, Hawaii, and Guam to the Philippine Islands. She arrived at Cavite, Luzon on 1 December.
In 1922, she sailed from Cavite on 11 October, visited Hong Kong from 14–28 October, and returned to Cavite on 1 November. Sailing from Manila on 15 May 1923, S-16 visited Shanghai, Chefoo, and Chinwangtao before returning, via Woosung and Amoy, to Cavite on 11 September. In the summer of 1924, she visited Shanghai, Tsingtao, Chefoo, and Chinwangtao, returning to Olongapo on 23 September. Departing Cavite on 3 November, she arrived at Mare Island, California on 30 December.
She remained at Mare Island in 1925-1926, and operated along the California coast in 1927, with a visit to Hawaii in July–August. From February 1928 into 1935, S-16 served in the Panama Canal area although she visited Baltimore, Maryland from 15 May-5 June 1933. Departing Coco Solo on 25 January 1935, S-16 was decommissioned at Philadelphia, Pennsylvania on 22 May.
S-16 was recommissioned on 2 December 1940. Following voyages to Bermuda and the Panama Canal Zone, she operated at Saint Thomas, United States Virgin Islands from December 1941-March 1942; in the Panama Canal area from April into August; and from New London during September and into June 1944, with operations at Casco Bay, Maine.
S-16 is in 265 ft (81 m) of water, upright with a 20° tilt to her starboard side. The Gulf Stream flow over her hull allows little coral growth and makes diving difficult to impossible. The wreck is accessible through large hatches both forward and aft of the conning tower. Both steel screws are covered by invertebrate growth.
A fictional USS S-16 appears in Edward L. Beach's 1955 novel Run Silent, Run Deep. In the novel she is taken out of decommissioned status, and re-commissioned and prepared for war by the heroes of the story, and then turned over to the Free Polish Navy.