With the loss, the Senators dropped into eighth place in the Eastern Conference.
"They were better than we were from start to finish," Senators coach Paul MacLean said bluntly. "They were harder at the nets ... at both nets than we were and executed way better than we did."
Penguins coach Dan Bylsma gave credit to his 36-year-old backup goalie's milestone performance.
"The numbers are significant. I think he's the 28th guy to get to 300 wins, and those are very impressive numbers as a goaltender. I thought he was very good in the net tonight and he was strong," said Bylsma, who also reached a milestone with his 200th NHL victory.
"When you look at career wins for coaches, I'm not sure where 200 wins is. It's a long way to go to some of the other good coaches, but certainly I'm happy to have gotten it and I got the puck."
Matt Cooke added an assist in his first game against Ottawa since his skate blade sliced the Achilles tendon of Senators defenseman Erik Karlsson on Feb 13. Karlsson was expected to miss the rest of the season following surgery, but the defending Norris Trophy winner is back practicing and could return to the Ottawa lineup soon.
Ottawa started the night in seventh place in the conference and could have leaped over the sixth-place New York Islanders. Instead, the Senators are now eighth, tied on points with the seventh-place New York Rangers.
The Penguins, who have already clinched first overall in the Eastern Conference, were without Sidney Crosby, Evgeni Malkin and Kris Letang, because of injuries and illness, while No. 1 goalie Marc-Andre Fleury was in Pittsburgh with his wife expecting their first child.
"I don't know why we started that way. We weren't taking them lightly," Senators defenseman Marc Methot said. "We're well aware (Pittsburgh) has a deep hockey squad, despite all their injuries. They capitalized on a couple of opportunities, and that was the difference."
The Senators didn't get any help from ninth-place Winnipeg, which beat Buffalo 2-1 and now trails the Senators and Rangers by just a single point, but both New York and Ottawa have a game in hand.
Winnipeg plays at Washington on Tuesday night, while the Rangers visit Florida. The Senators are off until Thursday's road game against the Capitals.
Although there was talk of revenge on Cooke for the Karlsson injury, not much came of it other than his refusal to fight Ottawa's Chris Neil in the opening minutes. The only rough treatment Cooke received was booing from fans every time he touched the puck.
"We're leaving here with two points and putting pressure on Chicago for first overall. I'm not even (thinking) about (the Karlsson injury) anymore," said Cooke, who added he's glad the game has come and gone. "It was a freak accident, and there was nothing I could have done to change it. It's an unfortunate part of this game. I'm happy he's having a great recovery, and hopefully he's playing soon."
Karlsson is back practicing with the Senators and could return to the lineup before the end of the regular season. ... The Penguins were first in the NHL with 3.34 goals per game heading into Monday. The Senators were second in goals against, allowing just 2.09 per game, just slightly more than Chicago. ... The Penguins (19-0-0) are one of just three teams (Rangers, Blue Jackets) that have not lost a game this season when leading after two periods. ... The Penguins are 22-3 against the seven other East teams currently occupying a playoff position. ... Crosby continues to lead the NHL in scoring despite having played nine fewer games than his closest pursuer. ... Senators D Chris Phillips is one assist shy of 200 for his career.