Connor Carrick, Tyler Bozak and Patrick Marleau also scored for Toronto, which picked up its third consecutive victory.
Van Riemsdyk recorded his third multiple-goal performance of the season to go along with his fourth three-point outing.
Sam Reinhart and Jason Pominville scored for the Sabres, who have gone winless in four of their last six games.
Toronto goaltender Curtis McElhinney stopped 38 of 40 shots to improve to 9-4-1.
Sabres goaltender Robin Lehner allowed four goals on 38 shots to drop to 14-25-9.
Van Riemsdyk scored twice in the first seven minutes to give Toronto an early 2-0 lead.
After a pass from Morgan Rielly, van Riemsdyk ripped a wrist shot from for his first goal 3:39 after the opening faceoff.
Three minutes later, he lifted another wrist shot past Lehner's glove side for his career-high 31st goal of the season.
Buffalo trimmed the deficit to 2-1 on a power-play goal by Reinhart with 5:31 remaining in the first period. He parked near the right side of the crease and punched in a loose puck for his 18th goal.
Toronto made it 3-1 on a long wrist shot by Carrick at 6:22 of the second period. That marked his fourth goal of the season and his first in the past 14 games. His last score came Jan. 20 against the Ottawa Senators.
A power-play goal by Bozak increased the Maple Leafs' advantage to 4-1 with 5:50 to play in the second period.
Pominville brought Buffalo within 4-2 with a power-play goal with 59 seconds left in the second period. The score gave the 35-year-old veteran five points (two goals, three assists) in his past five home games and 12 goals on the season.
Marleau finished the scoring with an empty-net goal in the final minute of the third period.
Maple Leafs center Leo Komarov exited the game because of a lower-body injury and did not return. The 31-year-old has 19 points (seven goals, 12 assists) in 71 contests this season.
--Field Level Media
Toronto | Buffalo | |
James van Riemsdyk 3 | Points | Evan Rodrigues 2 |
James van Riemsdyk 2 | Goals | Jason Pominville 1 |
James van Riemsdyk 1 | Assists | Evan Rodrigues 2 |
Tyler Bozak 1 | Power Play Goals | Jason Pominville 1 |
N/A | Short Handed Goals | N/A |
Curtis McElhinney .950 | Save Percentage | Robin Lehner .895 |
Curtis McElhinney 38 | Saves | Robin Lehner 34 |
Team | Shots | Goals | Power Play | Penalty Kill | Penalty Mins | Face Offs Won |
Toronto | 39 | 5 | 1-3 | 3-5 | 15 | 28 |
Buffalo | 40 | 2 | 2-5 | 2-3 | 11 | 30 |