Blake Comeau had pulled the Islanders into a 3-3 tie at 2:17 of the third period with his first goal since last March 29.
Taking advantage of a Philadelphia turnover, Comeau skated in and bounced a shot off Flyers defenseman Lasse Kukkonen and between the pads of goalie Martin Biron.
Arron Asham, Darroll Powe, and Jeff Carter also scored for Philadelphia, which is unbeaten in regulation in its last seven home games (5-0-2). Carter tied Buffalo's Thomas Vanek for the NHL lead with his 20th goal.
Andy Hilbert and Doug Weight also scored for the Islanders, who have lost four games in a row and six of their last seven.
Biron made 24 saves to win his ninth straight start going back to last season.
Yann Danis, starting his second game for New York since being recalled from Bridgeport of the AHL on Nov. 28, stopped 21 shots.
The Islanders scored twice in the span of 1:01 to take a 2-0 lead midway through the first period.
Hilbert redirected Chris Campoli's shot into the net on a power play at 9:23, and Weight put in a backhanded rebound at 10:24.
Asham got the Flyers to within 2-1 at 11:55 with his second goal of the season and first in 15 games. He scored on a one-timer from the slot after taking a pass from behind the net from Riley Cote, who outmuscled Islanders winger Jon Sim along the boards for the puck.
Powe made it 2-2 with his first NHL goal at 8:09 of the second period, hammering in a rebound after Danis couldn't handle Mike Richards' shot from the left circle.
Carter put the Flyers ahead at 16:02 of the period on a rebound of a shot by Scottie Upshall.
