USS S-21 (SS-126) was a first-group (S-1 or "Holland") S-class submarine of the United States Navy in commission from 1921 to 1922 and from 1923 to 1942. In 1928, she made the first gravimetric measurements ever made aboard a U.S. ship at sea. Prior to World War II, she operated in the Atlantic Ocean, Caribbean Sea, and Pacific Ocean, and after the United States entered the war, she operated off Panama. She then served in the Royal Navy as HMS P.553 from 1942 to 1944.