With the victory, the Sabres snapped a four-game skid (0-3-1) and Roy finished with two goals and an assist to enjoy his best outing in nearly four months.
"Finishing the chances is obviously key," said Roy, who was staring at an open side only to have Fleury kick out his left pad in preventing the Sabres from building a 3-1 lead with 7:20 left in the second period.
"He made a nice save. But at the same time, you want to finish that and get up three goals and close the game out," Roy said. "In the third period, I was really mad and I wanted to go out and score a goal."
It was a breakout performance for Roy, whose 5 points (2 goals, 3 assists) in three games matched what he had in his previous 20 (3 goals, 2 assists).
Pominville had a goal and two assists, while Paul Gaustad, Drew Stafford and Tyler Ennis also scored in helping Buffalo (25-27-7) move out of a tie with Carolina for last place in the Eastern Conference.
Deryk Engelland and Jordan Staal scored for the Penguins, who came out flat in failing to build off a 6-4 win at Philadelphia a day earlier.
Backup goalie Brent Johnson's season-long struggles continued. His record dropped to 3-7-2 after being yanked early into the second period after allowing three goals on 12 shots. Though Fleury provided the Penguins an immediate lift upon taking over, he eventually allowed three goals on 12 shots as Pittsburgh (33-21-5) squandered a chance to move ahead of the fourth-place Flyers in the East.
"It was a letdown for our team," Penguins coach Dan Bylsma said. "We knew exactly what team we were playing and what they could do and how they were going to play. We didn't execute and play that way. And early on, we gave up good opportunities, which they capitalized."
Fleury stopped the first seven shots he faced, including Patrick Kaleta's penalty shot, in giving the Penguins a chance to mount a comeback in cutting Buffalo's lead to 3-2 on Staal's power-play goal 5:05 into the third.
After squandering early leads in losing each of their past two games, the Sabres responded with Stafford and Roy scoring goals 2:22 apart.
"Today we finished the deal," Buffalo coach Lindy Ruff said. "I think the answer was getting the fourth one right away. That was the answer. ... We just kept coming."
Ryan Miller finished with 24 saves, including stopping Staal and Evgeni Malkin on breakaway attempts in the second period.
Pominville opened the scoring 52 seconds in, and Roy made it 2-0 before five minutes had passed.
The Sabres got off to a fast start despite having their pregame warmup interrupted when a light bulb broke just before Buffalo took the ice. Shards of broken glass were scattered across the ice in the Buffalo end, leading to several Sabres players requiring to have their skates re-sharpened.
The NHL allowed the Sabres additional time to warm up, which they did in the Penguins end. And the start of the game was delayed for a few minutes to allow the last few Sabres players time to have their skates sharpened.
"After a weird warm up, we stuck with it. Didn't want to make any excuses out of it," Pominville said. "We were able to get the lead, get it early and be good with it."
Material from wire services and team media was used in this report.
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