Already playing without Patrick Kane, the Blackhawks lost captain Jonathan Toews to an upper-body injury when he was drilled by Penguins defenseman Brooks Orpik. Toews was holding his left arm on the bench before heading down the runway for good in the second.
Blackhawks coach Joel Quenneville didn't believe the injury to Toews was serious, characterizing it as day-to-day.
"We'll get a better assessment tomorrow," Quenneville said.
James Neal and Lee Stempniak also scored for the Penguins, who won their second straight and snapped a three-game home losing streak. Marc-Andre Fleury made 25 saves in his 36th victory of the season.
Orpik's hit on Toews occurred with 6:30 remaining in the middle period. The two were going for a loose puck.
"It was a big hit," Blackhawks forward Patrick Sharp said. "You could tell he was trying to hit him hard. He knew who he was hitting. It's tough when you see your captain get hit like that."
Quenneville said he needed to see a replay of Orpik's hit. Bylsma said he only saw the hit live, and believed it was clean. Orpik agreed.
"There's no penalty, so I don't know," Orpik said. "I think that hit happens 10 times a game."
It's been a rough stretch for injuries for the defending Stanley Cup champions, who will be without star forward Kane for the rest of the regular season because of a lower-body injury. Bryan Bickell is out with an upper-body injury but is expected to return soon.
Blackhawks forward Marian Hossa played with Orpik with the Penguins during their run to the 2008 Stanley Cup Finals.
"(Orpik) is a heavy hitter," Hossa said. "That's his game. It's never easy to play against him. Sometimes he's on the borderline, but I know him as a fair guy and that's how I remember him."
The injury to Toews galvanized the Blackhawks, who dominated play in the third period. But Fleury held up just fine.
Crosby capped a 2-on-1 rush for Pittsburgh at 15:09 of the third, sending a wrist shot over the shoulder of Blackhawks goaltender Corey Crawford. He added an empty-netter with 1:16 left for his 36th goal and league-leading 99th point of the season.
"Obviously, they were coming and they put a lot of pressure on us," Crosby said. "They started to take a few more risks and we were able to capitalize."
Sheldon Brookbank scored for the Blackhawks, who have lost three straight in regulation for the first time since February 2012.
The Penguins and Blackhawks started the month at a snowy Soldier Field, part of the NHL Stadium Series. Chicago cruised to a 5-1 victory over Pittsburgh on March 1 in the beginning of a rough month for each team.
"We remember that snowy night in Chicago," Bylsma said. "They took it to us pretty good. We wanted to respond in this game and I think we did."
The Blackhawks and Penguins began the day with identical near-.500 March records and one win in each of their last four games.
Injuries to top forwards have played a role; Chicago played its sixth in a row without Kane, while former NHL MVP Evgeni Malkin missed his fourth straight for Pittsburgh. Both are expected to return for the postseason.
Chicago added another big name to the list after the loss of Toews.
"We've played 11 games in 19 days, it's a busy stretch of the year," Quenneville said. "There have been some stretches in the last three games that have showed that maybe this team needs a break."
Chicago carried the play early, Andrew Shaw hitting a post less than two minutes into the game. But Pittsburgh scored twice in 21 seconds, taking an early 2-0 lead.
Neal snapped a wrist shot past Crawford on a 2-on-1 and Stempniak got behind Johnny Oduya after a lead pass from Matt Niskanen and beat Crawford between the pads. Neal has 10 points in his last nine games against Chicago.
Pittsburgh had a chance to add to its lead in the second period, but came up short on two power-play opportunities.
Brookbank then delivered for the Blackhawks, cutting the deficit in half when he blasted a slap shot from the point behind Fleury.