Tage Thompson would finish with two goals and an assist as the Sabres completed just the second multi-goal playoff comeback in franchise history with their 4-3 win.
Buffalo's Alex Tuch would lead all players with an almost perfect 9.6 player rating for the game.
Despite the Sabres putting up 13 shots and 23 hits in the first period alone, it was the Bruins who entered the first intermission with the lead.
Morgan Geekie would rip one by Buffalo goalie Ukko-Pekka Luukkonen with a clear shot out in front of the net to make it 1-0.
The goal marked David Pastrnak's assist marked his 88th career playoff point, tying Wayne Cashman for ninth-most in Bruins history.
Thanks to a Jason Zucker two-minute minor for holding, the Bruins would start the second period with a man advantage for the first 50 seconds.
It would quickly switch up to a power play for the Sabres after Pavel Zacha was given a two-minute minor for holding, but Buffalo couldn't capitalize, nor could they on their second power play of the period just 12 minutes later.
It was the first time since Thanksgiving that the Sabres were held scoreless through the first two periods, despite outshooting Boston 27-13.
The Bruins only managed to put up four total shots in the second period alone.
A minute into the third, Geekie and Pastrnak would tally the assists for Elias Lindholm's first goal of the playoffs as the Bruins went up 2-0.
With 7:58 left to go in the game, the Sabres finally started to show life as they cut the lead in half, sending the Buffalo faithful into a frenzy inside and outside the arena.
It would take 33 shots to do it, but Buffalo's Thompson would make it 2-1 in his playoff debut with a wrap-around to finally get one past Jeremy Swayman.
Then, three minutes later on the Sabres' 37th shot on goal, they would tie it 2-2 as they continued their rally.
Who else but Thomspon to score his second goal of the game to put his Sabres in a position to complete the rally.
Following the goal, both the Sabres and Bruins received two roughing penalties each as both teams started to clash on the boards. The game remained a five-on-five with 3:47 left where the Sabres would complete the rally.
Mattias Samuelsson would put the Sabres up 3-2 as they scored three straight goals within the span of four minutes.
Tuch would send home the empty-netter on a Thompson assist to make it 4-2.
Pastrnak would score with just a few seconds left, assisted by Geekie, to make it a 4-3 game, but it wouldn't be enough as the Sabres take home the Game 1 victory after outshooting Boston 38-20 as both teams would combine for 91 hits.
Luukkonen would also earn his first career playoff win.
Game 2 between the Bruins and Sabres will take place on Tuesday, April 21st, at 7:30 p.m. Eastern time.