Nick Robinson, Gabriel Basso, Moises Arias, Erin Moriarty, Mary Lynn Rasjkub and Alison Brie will also feature in the indie comedy, reports Variety.
Robinson will take the lead role of Joe Toy, who with teenage friends Patrick (Basso) and Blaggio (Arias) heads out into the wilderness to build a house and live off the land.
Brie and Offerman will play Joe's sister and father, with Mullally as Patrick's overbearing mother, Moriarty as a divisive love interest for the friends and Rasjkub as a police officer sent to track them down.
Jordan Vogt-Roberts is directing Toy's House from a script by Chris Galletta.
Offerman and Mullally were married in 2003, as well as playing ex-couple Ron and Tammy in Parks and Recreation.
Shooting will begin on Toy's House in Cleveland in July.