Twenty-one-year-old winger Timo Meier scored the winner at 14:30 of the second period, breaking a 2-2 tie when he knocked home the rebound of a Joonas Donskoi shot from the slot for his first goal of the season.
Tomas Hertl opened the scoring for the Sharks with his first goal of the season at 2:15 of the first period, tipping home a Kevin Labanc shot on the power play.
Jason Pominville equalized for the Sabres (0-3-1) at 12:26 of the first period. He took a pass from Jack Eichel and wristed a shot past Sharks goaltender Martin Jones.
Chris Tierney gave the Sharks (1-2-0) a 2-1 lead after the first period when knocked home a Donskoi backhanded pass from behind the net past Sabres goalie Robin Lehner at 15:11.
Pominville scored his second of the game and fourth of the season, also assisted by Eichel, at 6:50 of the second to tie the game a 2-2.
Jones and Lehner each stopped 23 shots.
NOTES: San Jose was perfect on the penalty kill for a second straight game, stopping all three of Buffalo's power-play opportunities. The team has been successful its last 11 penalty kills. ... San Jose RW Timo Meier scored his second career game-winning goal and multi-point game. ... Sharks C Tomas Hertl had a team-high in shots on goal (five) and tied for the game-high in hits (five). ... D Josh Gorges and C Jordan Nolan drew back into the Sabres' lineup Thursday after both were scratched for the Monday home loss to the New Jersey Devils. ... D Viktor Antipin and LW Matt Moulson took their place in the press box, along with D Zach Bogosian, who has yet to play this season. ... The Sabres play the Kings in Los Angeles on Saturday, while the New York Islanders visit San Jose on Saturday.