In early years the rivalry was rather one-sided, with the Flyers being one of the NHL's best teams during the 1970s and the Penguins not catching up until selecting Mario Lemieux first overall in 1984.
The rivalry has been especially heated in recent years, as both teams have great rosters full of young, exciting talent. They have met in the playoffs six times, all since 1989, with the Flyers winning four series to the Penguins two.
In the past few seasons both teams have met in a number of heated battles, with young stars Sidney Crosby, Evgeni Malkin, Mike Richards, and Claude Giroux all trying to establish their authority.
Here are the most memorable moments from this great rivalry.
The Pittsburgh Penguins frustrated the Philadelphia Flyers all night during their 10-7 victory in Game 5 of this heated series. After Mario Lemieux set up Rob Brown for a pretty goal, Ron Hextall took issue with Brown's celebration and chased him down the ice.
A number of big fights would ensue as the Flyers tried to rally themselves. A number of individual fights increased tensions until things finally erupted around the 4:29 mark in the video.
The Penguins would go on to win the game, but the Flyers won the series in seven games.
With only a few games left in the regular season, both the Philadelphia Flyers and Pittsburgh Penguins were gearing up for the playoffs, and the intensity in this game was as high as it gets for a regular season matchup.
But the Flyers started running away with the game, ending up with an 8-4 victory. With about one minute left in the game, Joe Vitale threw a big, relatively clean hit on Danny Briere, and mayhem ensued.
The Flyers went after Vitale, Deryk Engelland beat up Wayne Simmonds and, most memorably, Peter Laviolette got up on the boards and screamed at the Penguins bench.
Penguins assistant Tony Granato got up and fired back at Laviolette, who was angry at head coach Dan Bylsma for having his checking line out there taking runs at the Flyers at that stage in the game.
It's not often you see such a good brawl, and you almost never see the coaches go at it like they do here. This was easily one of the most memorable moments of the entire 2011-2012 NHL season.
Just a couple weeks after their heated matchups at the end of the regular season, the Philadelphia Flyers and Pittsburgh Penguins faced off in the first round of the playoffs.
After winning the first two games in Pittsburgh, the Flyers came roaring back home with all the momentum. But the Penguins wouldn't go down easy, and the first half of the game was as fiery as it gets.
This brawl started with Sidney Crosby surprising nobody by taking a few cheap hacks at Ilya Bryzgalov's glove at the end of a play. As the original brawl died down, Crosby, master of the cheap shot-and-run, swiped away Jake Voracek's glove as Voracek bent down to pick it up.
The Flyers took issue with this, and it ended with a mini-fight between Crosby and Giroux, and Kris Letang absolutely thrashing an overmatched Kimmo Timonen.
After the Pittsburgh Penguins won two straight in the electrifying 2012 ECQF to make it a 3-2 series, Philadelphia knew they needed to put the series away back at home.
Claude Giroux had a breakout season, and was emerging as one of the superstars of the NHL. If Giroux is still at the top of the NHL in a few years, we'll look back on this shift as the true moment when his stardom was confirmed.
Giroux laid a big hit on Sidney Crosby right away, and then took the puck and rifled a shot over Marc-Andre Fleury's shoulder just 32 seconds into the game to give the Philadelphia Flyers an early 1-0 lead, which they never relinquished.
You'll be hard pressed to find a more exciting start to a game, or a louder building than the Wells Fargo Center after Giroux scores his goal.
This season marked the emergence of the Pittsburgh Penguins as a powerhouse in the NHL. Sidney Crosby and Marc-Andre Fleury both missed significant chunks of the season, but the Penguins showed resilience and won the Atlantic Division title for the first time in ten seasons.
They then went on to win their first two playoff series 4-0 and 4-1, bringing them to a matchup with the Philadelphia Flyers, whom they steamrolled 4-1.
Game five was especially one-sided, as the Penguins stormed out early and won 6-0 on their home ice, qualifying them for their first Stanley Cup since 1992.
Max Talbot shocked the hockey world last summer when he announced that he was leaving the Pittsburgh Penguins and signing with the Philadelphia Flyers. Talbot was beloved in Pittsburgh, and quickly became a fan favorite in Philadelphia, which only fueled the rivalry.
But another shocking announcement came when former Penguins star Jaromir Jagr announced that he was returning to the NHL not with the Penguins, as many had assumed, but with the Flyers.
These changes of city added a whole new element to the Flyers-Penguins rivalry, giving it an extra personal touch. In their first game back in Pittsburgh, Jagr added to the memory by scoring this dazzling backhanded goal.
Jagr is now with Dallas, but Talbot's place in Philadelphia will be a pressing subject in the rivalry for years to come.
The Philadelphia Flyers and Pittsburg Penguins met for a relatively routine game in the 2000 Eastern Conference Semifinals. The Penguins were up 2-1 in the series, and the Flyers were looking for a way to get back in the series.
The game would go on to set the modern era NHL record for longest game, as it stretched into five overtimes. At the 92:01 mark, Keith Primeau cut back next to the faceoff circle and rifled a shot just under the crossbar to win the series for the Flyers.
The Flyers would go on to win the next two games in the series, making Primeau's goal significant beyond the record books. It will forever be remembered as one of the best games in NHL history.