On February 9, 2001, the submarine struck and sank Ehime Maru, the Japanese fishery training ship operated by the Uwajima Fishery High School, near Hawaii. Nine crew members of Ehime Maru drowned including four high-school students.
The ensuing investigation revealed that the accident occurred while the submarine was demonstrating rapid surfacing for a group of American civilians on board, causing controversy and public outcry. Commander Scott Waddle, who was acting as skipper on Greeneville during the collision, accepted full responsibility and retired from the Navy following the investigation.
Construction of a memorial in Hawaii to Ehime Maru and her dead has been proposed.
On January 27, 2002, Greeneville collided with USS Ogden (LPD-5) during a personnel transfer off the coast of Oman, opening a 5-by-18-inch hole in one of Ogden's fuel tanks and spilling several thousand gallons of fuel. After the collision, both vessels left the area under their own power.