Guentzel had a three-point night but left after scoring 6:55 into the third period. Guentzel, who was selected to his first All-Star Game on Monday, tapped one into a partially empty net off Malkin's feed, then crashed hard into the wall following contact with Ottawa's Thomas Chabot.
Guentzel immediately went to the dressing room after getting his 200th career point.
"I hope he's not out long," Malkin said. "It didn't look good. But everyone understands it's hockey. It's tough. I need to play better next game if Jake doesn't play."
Penguins coach Mike Sullivan didn't have an update on Guentzel.
"It was really scary," Sullivan said. "Those are always dangerous when you fall that distance from the boards. He's being evaluated. We'll probably have more information on him (Tuesday)."
Malkin stretched his points streak to six games. He has seven goals and 24 points in his past 13 contests. Patric Hornqvist and Dominik Simon also scored the Penguins, who have won three straight and 10 of 12.
Tristan Jarry stopped 24 shots to win his sixth straight game. He has won eight of his last nine starts and allowed no more than two goals in 14 of 18 appearances this season.
Nick Paul scored twice for the Senators, who ended a five-game points streak. Paul has three goals in his last two games.
Marcus Hogberg made 28 saves for the Senators.
"We were unable to contain their top guys," Senators coach D.J. Smith said. "Defensively in our zone and off the rush, Malkin just kind of ate us up tonight."
Pittsburgh has won 14 of 22 games without captain Sidney Crosby, who has been out since November because of core muscle surgery. Crosby has recently started skating.
In 140 career games without Crosby, Malkin has 75 goals and 192 points. In 20 games without Crosby this season, Malkin has 11 goals and 32 points.
"We put him in a prominent role and he's responded in the right way," Sullivan said. "He's been a dominant player night in and night out for us. Given the circumstances this team is under, we need him to be that guy."
Malkin opened the scoring 27 seconds into the game when he beat Hogberg with a glove-side wrist shot during a 2-on-1. Guentzel assisted, giving him points in four straight. Guentzel has 12 goals and 29 points in his last 20 games.
Simon gave Pittsburgh a 2-0 lead at 11:44 of the first period. Simon was under pressure when he took a cross-ice pass and flipped a backhander past Hogberg from the side of the crease. It was his second goal in three games.
Paul scored at 4:21 of the second period for the Senators to make it 2-1, but Malkin regained Pittsburgh's two-goal advantage 1:41 later. Bryan Rust, who had the primary assist, has points in eight of his last nine games with seven goals and 15 points during that span.
Paul scored his second goal for the Senators at 15:58 of the second, but again, Pittsburgh immediately answered. Hornqvist scored 53 seconds after Paul's goal to give Pittsburgh a 4-2 lead entering the third period.
Pittsburgh's 16 home wins are the most in the NHL. ... The Senators have three wins in 22 games at Pittsburgh's PPG Paints Arena since the building opened in 2010. ... Pittsburgh has eight straight wins and points in 11 consecutive home games against Ottawa dating to Feb. 13, 2013. ... Ottawa D Ron Hainsey, who won a Stanley Cup with Pittsburgh in 2017, missed his fourth straight game with a lower-body injury. ... Pittsburgh D Justin Schultz missed his fifth straight game with a lower-body injury.
Senators: Host Florida on Thursday night.
Penguins: Host San Jose on Thursday night.
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