The victory was the third consecutive triumph for the Leafs after an 0-3 Western road trip. The win improved Toronto's record to 19-21-8.
The Leafs remain five points out of a playoff spot and 13th in the Eastern Conference, tied with Buffalo with 46 points. The Sabres have two games in hand.
Alexei Ponikarovsky's goal midway through the second period proved to be the winner, as he beat Sabres netminder Ryan Miller with a shot low to the stick side. The lanky left-winger was sent in on a partial breakaway after a great outlet pass from defenceman Hal Gill.
Alex Steen, Nik Antropov, and Jason Blake also tallied for the Leafs before 19,436 fans at the Air Canada Centre. Both Steen and Antropov's goals came via the power play, which went 2-for-5 on the night.
Vesa Toskala stopped 26 shots for his 16th win of the season. He allowed goals to Jochen Hecht and Daniel Paille, but was solid in the third period to preserve the Leafs victory.
The Leafs will play a late matinee game today when they visit the New Jersey Devils in East Rutherford. Toskala is expected to make his fifth straight start for Toronto, while New Jersey will counter with Martin Brodeur.
The Devils are coming off a 2-1 home loss to the Florida Panthers on Friday. New Jersey is led by the trio of Patrik Elias, Brian Gionta, and Zach Parise, who have combined for 97 points in 46 games.
The Devils sit sixth in the East with a record of 26-17-3 for 55 points.