Thomas Vanek and Drew Stafford had a goal and assist each for Buffalo in a game the Islanders made close by scoring three times in the final period. Jason Pominville added three assists in helping the Sabres (50-20-7) become the first team to reach the 50-win plateau this season and gain sole possession of first place in the NHL standings.
With 107 points, Buffalo moved one ahead of Detroit in the league race, follo the Red s' 4-3 shootout loss to Dallas.
Viktor Kozlov scored twice, including a goal in the final minute, and Tom Poti and Jason Blake added a goal each for the injury-depleted Islanders (36-29-12), who dropped to 2-5-2 in their past nine. They're struggling to remain in the playoff hunt entering the final week of the season.
Besides missing starting goalie Rick DiPietro (concussion) for a second straight game, New York was also minus high-scoring left-Ryan Smyth, who's listed day-to-day because of a leg injury.
Smyth has four goals and nine assists in 13 games with New York since being acquired from Edmonton at the NHL trade deadline last month.
DiPietro's injury hampers the Islanders the most, considering backup Mike Dunham allowed five goals on the first 10 shots he faced and was pulled after the first period. Dunham has lost five straight starts, a stretch in which he's allowed 24 goals.
The Islanders, who have five games left, remain tied with Carolina for 10th in the East in a tightly contested race between six teams separated by four points vying for the final three playoff spots.
Wade Dubielewicz, called up from the minors by the Islanders, stopped 17 shots and allowed only Dainius Zubrus' goal that put the Sabres up 6-3 with 7:29 remaining.
Buffalo took control by scoring three goals during a 3:01 span to build a 4-1 lead before the game was 11 minutes old.
Vanek opened the surge by scoring from behind the net, slipping the puck in with Dunham looking the wrong way.
Drury's first goal came when he one-timed in a shot from the left circle while Buffalo was enjoying a two-man power play. Stafford capped the run on the ensuing one-man advantage by collecting a rebound in front and backhanding it over a helpless Dunham.
Drury, with his second goal, and Derek Roy each scored on short-handed breakaways, the second time this season Buffalo has scored two short-handed goals in a game. Buffalo scored two empty-net short-handed goals in a 7-4 win over Toronto in November.
Notes: Smyth has four goals and nine assists in 13 games since the Islanders acquired him from Edmonton at the NHL trade deadline last month. ... Sabres C Daniel Briere had two assists to give him 92 points (31 goals, 61 assists), the most by a Buffalo player since the team had three with 96 or more points in 1992-93. ... The Sabres won their 27th home game for the second straight season. With one home game left, Buffalo will fall short of the franchise record of 30 set in 1972-73.