They'll play the 2022 Heritage Classic on March 13 at Tim Hortons Field in Hamilton, the NHL announced Thursday.
The outdoor showcase at the home of the CFL's Tiger-Cats returns to the league's regular-season schedule after games in 2019 in Regina, 2016 in Winnipeg, 2014 in Vancouver, 2011 in Calgary, and 2003 in Edmonton.
The Leafs-Sabres matchup will be the NHL's 35th outdoor game, and the third this season following the Winter Classic between the St. Louis Blues and Minnesota Wild on Jan. 1, and the Stadium Series between the Tampa Bay Lightning and Nashville Predators on Feb. 26.
Toronto will play its fourth outdoor game, while Buffalo makes its third appearance. The temperature in Hamilton on March 13, 2021, reached a high of 5 C.
The game will be broadcast on Sportsnet and SN Now at 3 p.m. ET.