Tuukka Rask made 23 saves in his second shutout of the season as the Bruins won the first of three meetings with Philadelphia.
Goals scored by Seguin, Chris Kelly and Daniel Paille in the first period were all Boston needed against the slumping Flyers.
One week after reaching .500 for the first time this season, the Flyers lost their third straight.
Ilya Bryzgalov stopped just three of the six shots he faced in the first period, but regained his composure and was the primary reason the game didn't turn into a rout. Bryzgalov kept Philadelphia within reach with saves on some great scoring chances for the Bruins, who outshot the Flyers 28-23.
The three-goal cushion has not always been good for the Bruins, who led 3-0 Tuesday at Washington and ended up losing 4-3 in overtime. Boston avoided any chance of blowing this one with tight defense, forcing the Flyers into mostly shots from the outside that were easy saves for Rask.
The Bruins scored on their first power play when Milan Lucic backhanded a pass across the crease to Seguin, who hit the open net and put Boston up 1-0 with 8:07 left in the first period. It was Seguin's eight goal of the season.
Kelly got free in the slot for another wrister with 6:32 left for his 99th career goal and it took less than a minute for the Bruins to strike again. Shawn Thornton forced a turnover at the blue line and set up Paille's breakaway goal with 5:49 left in the first that put Boston up 3-0.
Bryzgalov was pulled Thursday after allowing four goals as Pittsburgh rallied from a 4-1 deficit and won 5-4 in Philadelphia. Flyers coach Peter Laviolette left Bryzgalov in this time despite his struggles in the first period. His teammates didn't help him much Saturday with sloppy defense in their own end and the Bruins capitalized on it for their second and third goals.
Bryzgalov was sharper in the second period - and the Flyers needed him to be as Boston outshot Philadelphia 13-7 in the period.