The Chiefs said his return to the game was questionable.
Charles was injured when he was tackled by Indianapolis' Greg Toler on a 7-yard run. Charles was helped to the sideline, where he was examined by team doctors. He was later escorted to the locker room.
The sixth-year running back led the AFC in rushing with 1,287 yards and had an NFL-best 19 total touchdowns. He also led the Chiefs (11-5) with 70 receptions for 693 yards and seven TDs.
Charles was replaced by rookie Knile Davis.
Information from The Associated Press was used in this report.