They were joined by other officials Monday to discuss the game, in which one person is randomly assaulted and someone else films it with a phone.
Many cases have been reported in New York, and on Friday, Philadelphia police announced the arrest of a 15-year-old who attacked a male outside a pizza shop.
The teen has been charged with aggravated assault, criminal conspiracy and other crimes, KYW-TV, Philadelphia, reported.
Nutter said Monday anyone who takes part in the game will face charges from aggravated assault to third-degree murder.
"There's no excuse for this kind of behavior. It will not be tolerated here in the city. We will do everything we can to ... prevent, but if someone does engage, we will catch you. You'll be prosecuted, and your life will be changed dramatically," he said.
He also urged parents to do their part in discouraging children from participating in the game.
"This is not a game. You can seriously injure or possibly kill someone. Your child's life will be dramatically changed, and probably yours as well as a parent," Nutter said.