William Nylander had an assist to extend his season-opening point streak to 11 games, and Mitchell Marner had a goal and two assists for the Maple Leafs (5-4-2), who are 0-2-2 in their past four games. Joseph Woll made 35 saves.
"It felt like we beat ourselves," Toronto defenseman Mark Giordano said. "Every time we found a way to get back in the game, we gave them one. Pretty disappointing. We found ways in all aspects of the game to give them a freebie."
Matthews scored 17 seconds into the third period to tie it 3-3. He buried a shot from just below the right hash marks after taking a pass from Marner, who was behind the net.
Jordan Greenway put the Sabres back in front 4-3 at 3:11 when he tapped in the rebound of Casey Mittelstadt’s shot, but Matthews completed the hat trick at 7:26 to tie it 4-4 when he deflected a point shot from Giordano.
"Every time we were in control, the game was right there for us, we gave it back, right back," Matthews said. "They’re a very skilled team, very opportunistic team, and when you give them those chances, they typically make good.
"We haven’t played up to our capability for a full 60 minutes yet, and that’s on us to obviously figure that out."