After going down 2-1, the Blues battled back with three straight goals to take a 4-2 lead over the Penguins.
But a powerplay goal from Rickard Rakell (33) and a game-tying goal with just under a minute left in the third period from Rutger McGroarty (1) sent this one into overtime.
Robert Thomas (20) scored the game-winner for the Blues after going on the powerplay to extend their winning streak to a league-best 11 games with a 5-4 win.
The Blues (42-28-7) have now jumped the Minnesota Wild (41-28-7) in the Central Division as they now sit in fourth place.
Avalanche 7-3 Blue Jackets
The Blue Jackets went up 3-2 midway through the second period and the Avalanche took that personally.
They went on to score five straight goals, with one being Cale Makar's 30th of the season and the first time in his career.
Colorado clinched a play-off spot with the win and are holding on tight to their third-place standing in the Central Division.
Meanwhile, the Blue Jackets (77 points) now fall four points out of the Eastern Wild Card spot that the Montreal Canadiens (81 points) currently hold.
Canadiens 4-1 Bruins
Montreal earned their third straight win thanks to three straight goals to start the game.
The Bruins have now lost a brutal 10 straight games, being outscored 46-18, and now possess the worst record in the Eastern Conference at 30-37-9.
Boston is now in line to have the worst season in franchise history since the 2005-2006 season when they went 29-37-16.
Meanwhile, the Canadiens are looking to make their first play-off appearance since they went to the Stanley Cup Finals in 2021.
Around the league
The Dallas Stars earned their seventh straight win with a 5-1 victory over the Nashville Predators.
In Ottawa, the Senators took down the Lightning 2-1 thanks to goaltender Linus Ullmark's 31 saves.
Three straight goals in the third period lifted the Los Angeles Kings to a 4-2 win over the Utah Hockey Club.