Matthews broke a tie for the Toronto record for hat tricks in a season with six, passing Reg Noble (1917-18), Babe Dye (1924-25) and Darryl Sittler (1980-81).
Matthews also had his team-record 73rd multi-goal game, two more than Sittler. The American has 13 career hat tricks.
William Nylander added a goal and two assists to reach 500 career points, Bobby McMann had two goals and an assist, Nick Robertson finished with a goal and an assist and Jake McCabe and Tyler Bertuzzi also scored.
Martin Jones made 19 saves to help Toronto improve to 29-16-8. Timothy Liljegren had three assists and Mitch Marner, Max Domi and Matthew Knies each had two.
Toronto became the 15th team in NHL history to have hat tricks in three straight games after McMann had the first of his career Tuesday night against St. Louis and Matthews followed that with three goals Thursday night against Philadelphia. Matthews is the 10th player with six hat tricks in a season.
Ryan Strome had a goal and an assist for Anaheim, and Frank Vatrano also scored. Lukas Dostal allowed four goals on 18 shots in the first period before being replaced by John Gibson.
”We watched them skate around the ice for the better part of the first period,” Ducks coach Greg Cronin said. “Terrible start.”
On pace to become the first NHLer to reach 70 goals in a season since 1992-93, Matthews opened the scoring at 3:41.
Toronto went up 2-0 when McMann snapped his sixth on a power play at 6:06 before McCabe fired his fifth past Dostal, who stopped 55 of the 57 shots he faced Jan. 3 in a 2-1 overtime loss to the Maple Leafs in California.
Jones didn’t have much to do at the other end until Vatrano beat him for his 24th on a man advantage 59 seconds later.
The Maple Leafs restored their three-goal lead on another power play when Nylander buried his 28th — and 500th regular-season point — with 2:23 left in the period.
Gibson replaced Dostal following the intermission, and Matthews scored his second of the night 50 seconds into the second on another man advantage. Bertuzzi snapped a 19-game goal drought with his seventh to push Toronto to four for four on the power play at 2:51.
Matthews, who scored in overtime against Dostal last month, completed the hat trick at 5:39.
Toronto defenseman Morgan Rielly served the third contest of a five-game suspension for cross-checking Ottawa’s Ridly Greig for firing a slap shot into an empty net. Captain John Tavares sat out with what Leafs coach Sheldon Keefe described as a minor injury.
Up next for the Ducks: at Buffalo on Monday night.