Sam Lafferty scored a short-handed goal and had an assist, Maxi Domi and Kyle Clifford scored and Matthew Knies had a pair of assists for Toronto (1-1-1).
Defencemen Jeremy Davies and Henri Jokiharju scored goals for Buffalo (2-1).
The 25-year-old Timmins from St. Catharines, Ont., has two goals and four assists in two pre-season games. Domi scored his first goal in a Maple Leafs uniform after signing with the club in July.
Toronto’s goaltender Martin Jones stopped 10 of 12 shots in the game.
Uukko-Pekka Luukkonen turned away 25 of 28 over two periods before Michael Houser’s nine saves on 11 shots for Buffalo.
Clifford shovelled a cross-ice pass from Timmins by Houser for Toronto’s 4-2 lead at 2:18 of the third period.
Jokiharju’s point shot deflected off the post and in for Buffalo’s second goal of the game at 16:42 of the second.
The Maple Leafs led 3-1 by 14:06 when Domi came out of the penalty box after serving a high-sticking minor to cage a Timmins pass and score on a breakaway.
Buffalo’s power play turned the puck over in the offensive zone for Knies to skate it down ice and dish to Lafferty to finish at 12:36.
Toronto outshot Buffalo 14-4 in a first period that ended 1-1 at Joe Thornton Community Centre.
Timmins’ point shot clipped Luukkonen’s blocker en route to the net at 7:41, but Davies countered at 12:38.
The Maple Leafs are in Montreal for back-to-back games Friday and Saturday against the Canadiens.
The Sabres continue their pre-season Thursday in Pittsburgh versus the Penguins.