Coming Soon has confirmed that Busey will join the likes of Danielle Panabaker, Matt Bush, Chris Zylka, and David Koechner for the comedy horror film.
Although little is known about the movie's characters at the moment, it is believed that the film will see the flesh-eating fish attack the many visitors of a summer water park.
Dimension Films confirmed that work on a sequel to last year's Piranha 3D had been commissioned soon after the film's successful box office release.
Busey most recently appeared as a contestant on NBC's business reality show The Celebrity Apprentice.
Piranha 3DD is due out in cinemas on November 23.