USS S-43, a 1126-ton S-42 class submarine, was built at Quincy, Massachusetts. Commissioned in December 1924, she was based at Coco Solo, Panama Canal Zone during 1925-1927 and at San Diego, California for the next three years. Late in 1930 S-43 was sent to Hawaiian waters, her primary operating area until she was transferred to the East Coast in mid-1941.

Soon after the United States was brought into World War II in December 1941, S-43 went back to the Panama Canal Zone, where she conducted defensive patrols for a few months. In March and April 1943, the elderly submarine began a combat deployment to Australia. She made her first war patrol, in the vicinity of New Britain and New Ireland, during May and early June but her effectiveness was greatly hampered by numerous mechanical casualties. In July and early August, S-43 conducted another mission to New Ireland, in an effort to support Allied agents operating in Japanese-held territory. A third war patrol, into the Solomon Islands in September and October to assist with the Guadalcanal campaign, encountered no enemy targets.

Following that patrol, S-43 was sent back to Panama. She served in that area until April 1943, then operated off the Southern California coast until September. Overhauled in preparation for South Pacific anti-submarine training support duty, S-43 began this new assignment in April 1944 and performed similar service in Australian waters in January and February 1945. She returned to the U.S. West Coast in April and remained there for the rest of her active career. Decommissioned in October 1945, USS S-43 was sold for scrapping in December 1946.