The Iron Man actor had signed up to extend his comic book credentials with a turn as an animated supervillain who wipes out his archenemy, only to find life quite boring without an adversary to battle.
Downey Jr. recently walked out on the film due to "scheduling conflicts", leaving the project in jeopardy.
But the movie, directed by Tom McGrath, has been given a new lease of life after producers signed up Pitt and Ferrell to provide the voices for the main characters.
Comedic actor Jonah Hill has also joined Oobermind, according to Moviehole.net.
The film is slated for release in December 2010.