Defenseman Filip Kuba snapped a 4-4 tie with 1 minute, 11 seconds remaining when his point drive beat Bryzgalov to the short side. Ottawa's last goal was an empty-netter with 45 seconds left.
"When you're on the road leading by two, you can't be doing what we did today," said center Danny Briere. "We turned the puck over way too many times, and I just felt we were too soft. I hate saying that, and it usually doesn't happen with the Flyers, but today physically we got outplayed."
The Flyers are now 19-2-1 when they carry a lead into the third period. The other loss was in the Winter Classic to the New York Rangers.
Three Flyers rookies - Marc-Andre Bourdon, Sean Couturier, and Matt Read - scored goals to help the Flyers take a 4-2 lead. Former Senator Andrej Meszaros, playing in his 500th career game, also scored.
Colin Greening's crossing pass, intended for a streaking Jason Spezza in front, went off defenseman Matt Carle's stick and past Bryzgalov to get the Senators within 4-3 with 16:49 left. Carle was minus-4 in the game.
A little over three minutes later, all-star defenseman Erik Karlsson (plus-5) stripped the puck from Jaromir Jagr in Ottawa's defensive end, raced down the left wing on a three on one, and beat Bryzgalov from the left circle.
"I don't really know what happened there," said Jagr, who missed the two previous games with a groin strain. "He poked-checked it, and all of a sudden it's a three on one. I don't know where our defense went."
Briere said no one should point fingers at Bryzgalov.
"With all the turnovers we gave up, I don't think it's fair to blame Bryz," Briere said. "I think it's the easy answer to right away blame your goalie, but if you look in more depth, everywhere else we weren't good.
"It's tough because when you're the goalie, you're the last defense; you're the one that sticks out when you don't win, but with the amount of turnovers, and the physical play and hits that were nonexistent on our part."
On Karlsson's goal, Bryzgalov said he "tried to be patient" as the Senators had a three on one.
Bryzgalov said the NHL's move to make goalies wear smaller pads several years ago has made a major difference. With the old pads, he said, he would have stopped Karlsson's shot.
"There's a little space between the pants and pad, and he hit it right there, and the puck went through," he said.
Coach Peter Laviolette had started Bryzgalov on back-to-back days, hoping to get him into a rhythm.
"I was happy Coach gave me ice time tonight," Bryzgalov said. ". . . We didn't get the results, but we have to continue to work."
With the score knotted at 4, Ottawa goalie Craig Anderson made a key save on Brayden Schenn's tip with 5:15 to go.
"Our team, generally speaking, needed to play a better game, a smarter game against a team that forces a lot of turnovers," Laviolette said. "With the lead at 4-2, we needed to make better decisions."
Contact staff writer Sam Carchidi at firstname.lastname@example.org or @BroadStBull on Twitter.