Producers said Monday that Norton, whose recent credits include "The Mystery of Edwin Drood" and a Tony Award-winning turn in "The Seafarer" will play aging ranch handyman Candy.
The story by John Steinbeck centers on big-dreaming George, played by Franco, and the mentally challenged Lennie, portrayed by O'Dowd. Former "Gossip Girl" star Leighton Meester will play a beautiful temptress.
The play, which starts performances March 19 at the Longacre Theatre, has not been seen on Broadway in 40 years. Tony Award-winner Anna D. Shapiro will direct.
Norton is currently performing in Conor McPherson's "The Night Alive" at the Atlantic Theatre Company.