The submarine left Pearl Harbor at about 1:30 p.m. Wednesday for sea trials that are expected to take up to two days.
The Greeneville had been in dry dock at Pearl Harbor until earlier this month to undergo $2 million in repairs to its rubber exterior.
Nine people died when the Greeneville surfaced beneath the Ehime Maru nine miles off Waikiki while the submarine's crew was demonstrating a rapid-surfacing drill for a group of civilians.
The submarine is under the command of a new skipper. Capt. Tony Cortese takes over for Cmdr. Scott Waddle, who faces a possible court-martial for his role in the collision.
However, Sen. Daniel Inouye, D-Hawaii, told KITV4 News that he believes that Waddle should not face military prosecution.
The Greeneville was originally scheduled to deploy in June for six months to the Western Pacific.
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