HII's Newport News Shipbuilding will conduct the operation, which is expected to be completed in 2016.
"Although Newport News Shipbuilding has defueled and refueled many ships, including Enterprise, this is the first inactivation of a nuclear-powered aircraft carrier," said Chris Miner, NNS' vice president, in-service aircraft carrier programs.
"Our shipbuilders know Enterprise well and have enjoyed working on her over her decades of service. We are extremely proud of her great legacy, so it is with heavy hearts that we will work to retire this one-of-a-kind ship."
Under the award, the shipyard will defuel the ship's eight reactors and prepare Enterprise for its eventual transit to Puget Sound Naval Shipyard and Intermediate Maintenance Facility.
The USS Enterprise (CVN 65) is already at Newport News, where it was built and launched in 1960.
The contract given by the Navy is a cost-plus-incentive-fee vehicle.