The Italian manufacturer had already confirmed Andrea Dovizioso and Nicky Hayden as their factory riders for next season, as Valentino Rossi leaves to return to Yamaha.
Spies has endured a torrid 2012 season with the factory Yamaha squad, having been severely hamstrung by several bike failures.
The 2009 World Superbike champion, who currently lies 10th in this year's standings after a run of three consecutive retirements, had hinted he would leave MotoGP after becoming disillusioned with the series.
But the Texan will instead remain in the top class with a Pramac team who will get the latest spec bike as Ducati look to get a grip on the development of the temperamental Desmosedici.
Spies will be partnered by Italian Iannone, who will make the step up from the Moto2 class where he currently lies fourth in the points standings after taking two wins so far this season.
A Ducati statement read: "Ducati announces that it has signed an agreement with American Ben Spies and Italian Andrea Iannone to compete in the 2013 MotoGP World Championship.
"At the same time, the partnership has been renewed between Ducati and Pramac Racing, which will continue to be entrusted with management of the satellite team. The two riders, who have a direct link with the company, will be supplied with official equipment.
"This agreement will enable additional important support in the development of the Desmosedici MotoGP project, offering a further opportunity in the process of improving the performance of the Italian bike."