The film, with a script by Todd Luiso and Jacob Koskoff, will be directed by Justin Kurzel and produced by "The King's Speech" and "Shame" producers See Saw.
"Macbeth" will mark the second collaboration of Fassbender and Portman, who recently finished filming Terrence Malick's latest, currently untitled film about the Texas music scene.
Portman reportedly has long wanted to play Lady Macbeth and considered performing in a stage production of the play.
Macbeth has been adapted for the screen several times. Roman Polanski directed a version in 1971, and Orson Welles directed and starred in a 1948 film. The play was recently staged in London’s West End starring James McAvoy, who was nominated for an Olivier Award for his performance, and Alan Cumming is currently starring in a one-man adaptation on Broadway.