Nelson will also co-star in and direct the comedic thriller, slated to begin shooting in the spring, Variety.com reported.
Norton and Nelson worked together on "The Incredible Hulk," which has been filmed and is now in post-production.
In their latest collaboration, Norton will play twin brothers -- one a classics professor, the other a career criminal, the trade paper said.
"The challenge of playing twins for an actor is very special, and I was very flattered that Tim sent 'Leaves of Grass' to me," Norton said. "I liked it so much, and felt so strongly that it was a film Tim understood to his core, that I took it to my partners and suggested we produce it. This is exactly the kind of personal filmmaking that we set out to support."
Nelson previously directed "The Grey Zone" and "O" and starred in "The Good Girl" and "O, Brother, Where Art Thou?"
Norton is best-known for his roles in "Primal Fear," "Rounders," "Fight Club" and "The Painted Veil."