It will be developed by Human Head Studios, the team responsible for the original game, and will run an engine supplied by id Software.
The follow-up to the 2006 first-person shooter, Prey saw members of a Native American reserve abducted by an alien spaceship, and featured portal and gravitational gameplay mechanics.
"We are thrilled to be working with Bethesda on Prey 2," said project leader Chris Rhinehart.
"Prey 2 will provide gamers the opportunity to explore a new facet of the Prey universe, one that offers fast-paced action in an open, alien world.
"We're excited to show gamers the title we have been working on and hope they will be as excited by this title as we are."
Prey 2 will be available in 2012.