Guerin, at 38 the oldest player on a mostly young team, took Sergei Gonchar's pass from center point and skated toward the net from the low left circle, faked a pass and beat goalie Martin Biron on a shot that deflected off the left post and into the net 18:29 into overtime.
Guerin also scored the goal that tied it at 1 late in the second period, and Evgeni Malkin tied it at 2 with 3:37 remaining in the third after rookie Darroll Powe's goal put the determined Flyers up early in the period.
The Penguins will take a 2-0 series lead to Philadelphia for Game 3 on Sunday, as they did in winning last year's Eastern Conference finals against the Flyers.
The overtime game was the first between the in-state rivals since Keith Primeau's goal decided the Flyers' 2-1, five-OT win that started on May 4, 2000, and ended in the early morning hours of May 5. That game was the NHL's longest in the past 73 years.
This game was much shorter.
The Flyers initially went on the power play in overtime when Hal Gill was called for cross-checking, but an identical penalty on Mike Knuble and a slashing call on Claude Giroux 30 seconds later gave Pittsburgh a two-man edge that would have lasted 1:29. Guerin scored with 27 seconds left in the two-man.
HURRICANES 2, DEVILS 1 (OT)
In Newark, N.J., defenseman Tim Gleason scored his first NHL playoff goal on a slap shot at 2:40 of overtime, tying the teams' first-round playoff series at a game apiece.
Gleason's shot from the right point appeared to hit the skate of Devils defenseman Niclas Havelid and carom past defenseless goalie Martin Brodeur.
Eric Staal, who provided a screen in front of Brodeur, scored the other goal for the Hurricanes. Carolina, which lost the series opener 4-1 on Wednesday, seemed to find its game in the second period Friday.
Zach Parise tallied for the Devils, who lost captain Jamie Langenbrunner to a lower body injury in the second period.
Brodeur, who finished with 30 saves, wasn't so lucky the second time as Carolina beat New Jersey for the fifth time in five postseason overtime games. Carolina's Cam Ward made 33 saves for the win.