Jack Eichel scored twice in the third period, and Sam Reinhart had a goal for the Sabres (17-8-4), who have lost four straight following their 10-game winning streak, including 2-1 at the Nashville Predators on Monday. Linus Ullmark made 26 saves.
"We just played two of the top five teams in the NHL on a back-to-back, and we traveled," Eichel said. "I thought we played a great game tonight. Obviously, they get the extra point and it's frustrating, but give us credit. … They're sitting here waiting for us. It's not easy, and I thought we brought a lot of compete and effort."
Eichel tied the game 2-2 at 2:39 when he one-timed Rasmus Ristolainen's pass from the bottom of the left face-off circle.
Eichel capitalized on a Maple Leafs turnover to put the Sabres ahead 3-2 at 12:57 with a shot from the slot.
"He's been playing terrific," Buffalo coach Phil Housley said. "Tonight, he was a beast again. It's good to see him finally find the net again. He's contributing in so many other ways, not only just with scoring goals, but playing a 200-foot game."