Zegras scored his second goal at 14:23 while on a power play to put the Flyers ahead 2-1. York faked a shot in front and instead gave Zegras the puck with a no-look pass at the right face-off dot, where Zegras scored with a sharp-angled wrist shot.
"I missed last year's game (in Philadelphia), but I heard all about it and I was fired up to play in this one," Zegras said. "The boos were great but the cheers were even better."
York pushed the lead to 3-1 at 1:15 of the second period. He collected a pass at the point, cut back to his forehand and threaded through a long-range shot.
Ducks forward Ross Johnston was assessed a major penalty and game misconduct for interference after colliding with Jamie Drysdale at 2:39 of the second period. Drysdale did not return.
The Ducks killed the major penalty, but Travis Sanheim scored on a one-timer from above the right circle off a face-off win to make it 4-1 at 14:40.
Killorn scored for the second straight game with a snap shot from the inside edge of the left circle while on a power play to cut it 4-2 at 1:25 of the third period.
Anaheim killed a 45-second, 5-on-3 power play later in the third before Grebenkin scored into an empty net with 1:14 left for the 5-2 final.
The Ducks committed 11 total penalties, killing eight of the nine power plays for Philadelphia.
"We have to be disciplined, for sure," LaCombe said. "We can't win hockey games taking (11) penalties, whatever it was."
The Flyers also lost forward Bobby Brink to an upper-body injury following a hit by Ducks forward Jansen Harkins at 2:32 of the first period. Flyers coach Rick Tocchet did not have an update on Brink or Drysdale after the game.
Anaheim defenseman Ian Moore left at 7:47 of the third period after taking a hit from Philadelphia forward Garnet Hathaway.
NOTES: Flyers forward Matvei Michkov did not play after getting hit in the foot with the puck in a 5-2 win at the Edmonton Oilers on Saturday. Grebenkin took his spot on the third line after being scratched against the Oilers. ... The Flyers are 7-for-54 (13.0 percent) on the power play in their past 17 games. ... Anaheim goalie Ville Husso backed up Dostal after he was recalled from San Diego of the American Hockey League earlier Tuesday. Petr Mrazek was injured in a 7-4 loss to the Washington Capitals on Monday.