The Bridget Jones actress will also star in 4 1/2 Minutes alongside Johnny Knoxville.
The film will be financed by Kevin Frakes's PalmStar Media Capital and is written by Warrior's Anthony Tambakis.
4 1/2 Minutes is based on real-life stand-up comic Dov Davidoff, who also shares a story credit.
It centres on Jimmy Bennett (Knoxville), a commitment-phobic comedian who starts a job taking care of a genius son of a single mother (Zellweger).
The film is set in New York City, with production expected to start in February.
Frakes will produce, alongside Zellweger and Tambakis, with Raj Brinder Singh executive producing.
Zellweger and Tambakis previously worked together on the recent Lifetime pilot Cinnamon Girl, while she will also appear in the Broadway adaptation of The Hustler, which is scripted by Tambakis.
"It´s great to be working with Renee as a partner on this project," said distributor K5 International co-founders Oliver Simon and Daniel Baur. "It's a wonderful opportunity to support her as she moves into her first directing role."
K5's Carl Clifton added: "Renee Zellweger is unique. She's one of the very finest and highest-profile comic actresses working today but she has an amazing range too and, as this film and the actor/director role she is taking on it will show, she is also is one of the industry's most versatile and brightest talents."