Karlsson is the 23rd defenseman in NHL history to reach the milestone and second active to do so, joining Brent Burns of the Carolina Hurricanes (261).
"It's obviously a nice one,” Karlsson said. “I don't know if it is actually a milestone though, but I'll take it. Been fortunate to play for a long time and score some goals over the years. Hopefully, I've got another 100 in me."
Tristan Jarry made 26 saves for his second shutout this season and 21st in the NHL. Kevin Hayes scored twice, and Bryan Rust and Danton Heinen each had two assists for the Penguins (32-35-12), who lost 3-1 at Chicago on Sunday to begin the home-and-home set.
Spencer Knight made 22 saves for the Blackhawks (22-46-10), who have lost 13 of 15 games (2-11-2) dating to March 8.
“I don’t think they let me down,” Chicago coach Anders Sorensen said. “They let themselves and their teammates down, right? I mean, I think that’s the biggest part of it. We’re a group here. It’s not me or them. It's a group thing. We let each other down today.”
Each team has been eliminated from contention for the Stanley Cup Playoffs.
Sidney Crosby put Pittsburgh ahead 1-0 six seconds into a power play at 19:44 of the first period with his 31st goal of the season and 12th in 14 games. He turned in front of Chicago defenseman Alex Vlasic to chip in a pass from Rickard Rakell.
Crosby extended his home point streak to 14 games (20 points; nine goals, 11 assists).
“Listen, these guys have done a great job,” Penguins assistant coach David Quinn said. “When you have this type of talent, you have a great chance to have a good power play. These guys have certainly done a great job working together.”
Karlsson then made it 2-0 at 4:45 of the second period with his 11th goal, taking a pass Ville Koivunen slid above the crease for a wrist shot near the left post.