Lane, 46, will play fading screen star Alexandra del Lago, a role immortalized by Geraldine Page in the original stage and screen productions of the play.
The show will run at Chicago's Goodman from Sept. 14 to Oct. 25, 2012, with opening night set for Sept. 24.
The production will be directed by David Cromer and will co-star Finn Wittrock ("All My Children") as del Lago's youthful gigolo Chance Wayne.
Cromer directed a 2008 revival of "Our Town" at Chicago's Chopin Theatre and off-Broadway. He was previously slated to direct a Broadway version of "Sweet Bird of Youth" with Nicole Kidman and James Franco that was scrapped last year.
Lane received an Academy Award nomination for her work as a cheating wife in 2002's "Unfaithful" and will appear in the upcoming Superman reboot "Man of Steel." She is best known for her screen roles, but appeared on stage as a teenager in Joseph Papp's production of "The Cherry Orchard" with Meryl Streep.