The Hangover star Ed Helms has also signed up for the Fox Searchlight project. Miguel Arteta will direct.
The movie follows the story of a "wholesome and naive man" from Wisconsin (Helms), who is forced to represent his company at a regional conference in Cedar Rapids, Iowa, where he is shocked by the big-town experience.
Reilly is cast as another conference attendee, who is using the event as an excuse to cut loose while away from his family.
The Step Brothers star's other upcoming projects include comedy horror Cirque du Freak and an untitled Duplass brothers comedy.