The Twentieth Century Fox film was originally known as the "Alien" prequel. It's not clear if the name change means that Scott's film will still focus on flesh eating extraterrestrials.
The Oscar-winning Theron is best known for her roles in "Hancock" and "Monster." She joins Michael Fassbender and Noomi Rapace.
Scott will also produce the film, along with Tony Scott, David Giler and Walter Hill.
The screenplay is credited to Damon Lindelof and Jon Spaihts.
News of Theron's negotiations was first reported by Variety.