Busch was taken to Halifax Medical Center in Daytona, where he had surgery Saturday night for a compound fracture in his lower right leg. He also has a fractured left foot.
Truck Series drivers Matt Crafton will replace Busch in his No. 18 Toyota in the Daytona 500, Joe Gibbs Racing announced. A return date for Busch has not been determined.
Kyle's brother, Kurt, also will miss the Daytona 500 after being suspended by NASCAR. It will mark the first time since 2000 that one of the Busch brothers has not been in the Daytona 500.