Tony Award-winning director Jack O'Brien is directing the play, which opens Nov. 3 at the Music Box Theatre.
Greer (left), a familiar face on television and in film, is making her Broadway debut in the comedy. She played opposite George Clooney in 2011's "The Descendants" and has appeared on television in "Two and a Half Men," "Californication" and "Arrested Development."
Hamilton was last seen on Broadway in 2006-07's "The Coast of Utopia" trilogy, which also was directed by O'Brien. Houdyshell received Tony Award nominations for last year's revival of "Follies" and for her 2006 Broadway debut in "Well."
The new comedy from Rebeck, the creator of the NBC series "Smash," revolves around a prodigal son whose unexpected return home throws his family into a frenzy.
Jeffrey Finn, John N. Hart Jr., David Mirvish, Amy Nauiokas, Ergo Entertainment and the Shubert Organization are producing.
For the Record: An earlier version of this report incorrected stated that Theresa Rebeck is the co-creator of "Smash." She is the sole creator of the NBC series.