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The Pittsburgh Penguins had won six in a row, hadn't lost at home since late November, and won 17 of 19 games.
Their 1-0 lead in the third period against the Seattle Kraken was insufficient.
Jared McCann's late game-tying goal sparked the rally, Philipp Grubauer improved to 4-1 in his last five appearances, and Adam Larsson sniped the first walk-off winner in Kraken history, a 2-1 overtime victory over the host Penguins before a sellout crowd on Thursday at PPG Paints Arena.
The Kraken, winning for the fourth time in six games (4-2), notched their first road victory since Dec. 14 at San Jose and finished a two-game season series with Pittsburgh at a 1-1 split.
"It's a good win in this building," said Kraken head coach Dave Hakstol.
"It's a hard place to win. For us, it's an enjoyable win, but it's one that we had to work for. Our game didn't change a whole lot from the drop of the puck to the winning goal in overtime."
Larsson earned his second game winner of the season.
Evgeni Malkin scored a power play goal for the Penguins, minutes after Vince Dunn rang a potential 1-0 lead off the post, and put his team up 1-0 on a blast from the point at 8:41 of the third.
Dunn then took a face-off win and fired a shot off McCann's stick for a 1-1 tie with 3:56 left in regulation.
Larsson ended the game on a wrister past All-Star Tristan Jarry from the slot, set up by Alex Wennberg.
"The trick is just to maintain simplicity," said Hakstol. "For our team, it's a good formula for success. We talked all year long we have to be comfortable in close, tight hockey games."
The Kraken will move onto the second game of the four-game trip on Saturday, 11:00am PT against the host New York Islanders.