Former works Yamaha rider Spies has been recruited to the revamped Pramac squad - which now enjoys full works support - to join Moto2 graduate Andrea Iannone.
Andrea Dovizioso and Nicky Hayden will ride the factory entries.
Ducati MotoGP project director Paolo Ciabatti said: "We're very confident that Ben Spies will be able to use his talents to help us with the development of the bike and to achieve the results we're after more quickly."
Spies said joining Ducati was a dream move for him.
"I am excited to be a part of the Ducati family," he said. "This is something I've wanted from the beginning of my racing career.
"My team and I have our work cut out for us and new goals to meet, but we'll benefit from factory support and Audi coming on board.
"Ducati has four strong riders with different styles, which should improve the Desmosedici and bring it back up to the top where it belongs."
Spies won the World Superbike title for Yamaha as a rookie in 2009, before being brought into the firm's second-string MotoGP squad Tech 3 for the following season.
Two years in Yamaha's factory line-up followed, but only brought one victory, with Spies deciding to leave Yamaha during a frustrating 2012 campaign.