Bill Hader, Brie Larson, Barkhad Abdi, Mike Birbiglia, Jon Glaser, Vanessa Bayer, John Cena and Ezra Miller are also on board.
Schumer penned the script. Plot details are being kept under wraps.
Apatow will also produce for his Universal-based Apatow Productions along with Barry Mendel. Senior VP of production Erik Baiers oversees for the studio.
The news comes after Universal acquired rights to a film revolving around James’ days playing high school basketball that Rachel and Terrence Winter are producing. He is repped by WME and LRMR.