With the game tied at 1 with 13 minutes to go in the second, Buffalo's offense received a much-needed jolt when Toronto goalie Vesa Toskala muffed the Buffalo defenseman's soft wrister from the left point.
The floating shot handcuffed Toskala by going off his glove before trickling in, giving Lydman his first goal since March and the Sabres a 2-1 edge.
"Usually they're really pretty," joked Lydman, who has 30 goals in 612 career NHL games. "I can't remember scoring a goal like that before."
To that point, Toronto had outshot the Sabres by a 16-6 margin, and had complete control of the game. But the goal seemed to rattle Toskala, who surrendered the four second-period goals on just six shots.
"I was just thinking ahead," he said. "I was thinking of a quick plan. It hit my thumb and went in. It was a bad time to give up that goal. The game was 1-1. Everybody makes mistakes."
Toskala was pulled when Matt Ellis' wrist shot from the left circle made it 4-1 with 7:12 left in the second.
Derek Roy and Mike Grier also scored in the middle period for Buffalo (21-10-2) in its eighth straight win over the Maple Leafs. Thomas Vanek also scored, and Grier and Lydman added an assist each for the Sabres, winners of five of six.
Miller stopped all but one of the 20 shots Toronto fired his way in the third period.
"As a goaltender you feel bad for Vesa on that play," he said. "You know what he's trying to do ... he's looking for an option. But playing against the Maple Leafs, I don't really care too much."
Toskala, making his seventh straight start, finished with six saves before giving way to Jonas Gustavsson, who gave up a goal on 17 shots in his first appearance since undergoing a heart procedure in early December.
"When you make a mistake like that, you've got to buckle down. Unfortunately [Toskala] didn't," Toronto coach Ron Wilson said about making the change in net.
Toronto came in having given up the most goals in the NHL.
The Sabres began their second-period blitz when Roy one-timed a shot from the slot that got past Toskala at 1:32.
Grier scored just 2:12 later when Tim Kennedy's feed from the left circle went off Grier's left leg and in.
Stalberg opened the scoring with his first NHL goal just 3 minutes into the game. From the lower portion of the right circle, Stalberg's wrist shot eluded Miller, who was screened by Ellis.
The teams will meet again Monday in Toronto, where the Sabres have won seven straight. ... This was the only road game for the Maple Leafs during a six-game stretch. ... Buffalo C Paul Gaustad returned after missing the last 10 games because of a knee injury. ... Toronto D Luke Schenn played after being a healthy scratch the past three games. ... Buffalo has outscored the Maple Leafs by a 32-10 margin in its eight straight wins over Toronto. ... Miller won his 20th career game against the Maple Leafs, the most against any opponent. ... It was the fourth time in eight games the Maple Leafs have allowed at least five goals.