Scheduling conflicts forced the "X-Men: Days of Future Past" star to bow out of the project, paving the way for Segel to climb on board as Robert Redford's onscreen son, reported Deadline.
Actress Rooney Mara, who has been attached to the film since last year, will portray the Forgetting Sarah Marshall actor's love interest in "The Discovery", which is set in a world where the afterlife has been scientifically proven.
Charlie MCDowell, the son of actors Malcolm MCDowell and Mary Steenburgen, co-wrote the film and will also serve as director.
"I couldn't be happier to be working with Charlie," said co-producer James D Stern of Endgame Entertainment.
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"Robert Redford, Jason Segel and Rooney Mara are three exceptionally talented actors and make the project all the more exciting."
The new film will be MCDowell's second feature release after making his directorial debut in 2014 with critically-acclaimed psychological thriller "The One I Love", which starred Elisabeth Moss and Mark Duplass.
"The Discovery" is also his first project with girlfriend Mara, who he has been dating since 2010.