Colton Parayko scored 19 seconds later on a wrist shot to make it 3-1 at 13:49, chasing DeSmith.
"Had some timely goals. We had a chance to win it there," Blues captain Ryan O'Reilly said. "We were in a good spot in that third period. Had a chance to win a game. Unfortunately, we didn't. It's frustrating. By no means was it our best game. That happens, but it was there for the taking."
Rust took a pass from Crosby for a wrist shot, cutting it to 3-2 at 15:46 of the second. Five of his seven goals this season have come in the past two games, including three in an 8-5 win against the San Jose Sharks on Sunday.
"I'm getting some confidence back," Rust said. "I said it after last game, I'll say it again, those extra practices I got in with the canceled games, or the postponed games, I think that helped a lot. … Get that confidence back shooting the puck, things like that, I think that did go a long way."
NOTES: St. Louis played its first game since defeating the Minnesota Wild 6-4 in the 2022 Discover NHL Winter Classic at Target Field on Saturday. … Penguins forwards Kasperi Kapanen and Blueger returned after missing an 8-5 win against the San Jose Sharks on Sunday while in COVID-19 protocol. Kapanen had three shots on goal in 14:54 of ice time; Blueger had one assist and one shot on goal in 15:43. … Guentzel, who had two assists, has at least one point in 15 straight games (23 points -- 13 goals, 10 assists) since last being held without one Nov. 11. He missed five games with an upper-body injury from Dec. 10-19 before returning Sunday. … Kyrou has 13 goals in 30 games this season, one goal shy of his NHL career-high of 14 in 55 games last season.