Playing on the checking line against Anaheim's top line, Knuble got his first hat trick in 707 career games to help the Atlantic Division-leading Flyers improve to 13-3-1 since they were in last place on Christmas.
"It's a great feeling," Knuble said.
The defending Stanley Cup champion Ducks have lost six straight since going 8-0-1, including a 1-0 shootout loss at St. Louis on Friday night. Anaheim hasn't scored in seven periods and one overtime. It's been 155:20 since Corey Perry scored in the second period of a 5-1 loss at Minnesota on Wednesday.
A two-time 30-goal scorer in 10-plus seasons in the NHL, Knuble gave fans a reason to toss their hats onto the ice for the first time in his career when he scored his 19th goal on a slap shot from above the right circle to give the Flyers a 3-0 lead in the third period.
He was outstanding on the opposite end of the ice, helping shut down Todd Bertuzzi, Ryan Getzlaf and Perry.
"They're three great players and we kept them off the board," Knuble said. "It was our night. Next time might be theirs."
The Ducks are having so much trouble offensively that they're missing easy opportunities. Getzlaf shot wide at an open net after Biron ranged far outside the crease to get a loose puck and turned it over in the second period.
"We just can't find a way to create offense," Ducks coach Randy Carlyle said. "We had opportunities. We have to stay positive. We're not happy with the outcome, but we can take solace that we worked hard."
Biron preserved his 21st career shutout with a pad save on a point-blank shot by Francois Beauchemin midway through the third period.
"First thing you see with Marty when he's really sharp is his rebounding control," Flyers coach John Stevens said. "He made some key saves at key times and he looks like he's growing in confidence."
Knuble put Philly ahead 1-0 almost 6 minutes into the second period. Ducks goalie Jonas Hiller stopped Scottie Upshall's slap shot, but the puck bounced behind him. Hiller turned and almost gloved it, but Knuble poked it in.
Derian Hatcher initially was awarded the goal and he celebrated in the penalty box after getting into a minor scrum with Bertuzzi. Knuble got credit for the goal during the intermission.
Knuble scored on the power play with 10 seconds left in the second, deflecting in Mike Richards' shot from the point.
The Ducks are almost halfway through an eight-game, 15-day road trip, the longest continuous stretch away from home in team history.
"We have a couple of days to get rested before the next one. We've got to scratch and claw to play well," defenseman Scott Niedermayer said.
Notes: Flyers GM Paul Holmgren went to Sweden, presumably to speak with Peter Forsberg about returning to Philadelphia. Forsberg, a former league MVP who won two Stanley Cups with Colorado, played 1½ seasons with the Flyers before he was traded to Nashville last year. ... Teemu Selanne, who came out of retirement and signed with the Ducks on Monday, was a healthy scratch for the third straight game. He could be ready to play against the Islanders on Tuesday. ... Biron's previous shutout was against New Jersey on Oct. 18.
