Penguins captain and leading scorer Crosby left the contest early in the third period after a collision with Blackhawks defenceman Erik Gustafsson.
Crosby remained on the ice after the contact and blocked a shot off his right skate then headed for the bench and walked gingerly down the hallway to the Penguins dressing room.
Guentzel beat Chicago goalie Corey Crawford between the pads, and Jared McCann also scored in the shootout, hammering a blast past Crawford's stick.
Crosby is expected to be examined by team doctors on Sunday.
"He's being evaluated right now for a lower body injury. We'll have more information probably Monday," head coach Mike Sullivan said following the game.
The Toronto Maple Leafs also lost their top scorer on Saturday night when winger Mitch Marner left with an ankle injury in the second period of Saturday's 3-2 shootout loss to the Philadelphia Flyers.
Marner took an awkward fall over Flyers Carsen Twarynski's stick, then struggled to get back on his skates and eventually crawled off the ice.