The comeback win snapped Anaheim's seven-game winless skid and moved the club to 2-1-0 on home ice this season.
Zegras, Jakob Silfverberg, Dmitry Kulikov and Frank Vatrano scored for Anaheim. Derek Grant, Isac Lundestrom, Troy Terry, Frank Vatrano, Kevin Shattenkirk and Ryan Strome added assists.
Zegras' OT winner was the second such goal of his career and his sixth game winner. The 21-year-old center has six goals in nine games this season.
John Gibson stopped 32-of-35 Toronto shots to earn his second win of the year. Gibson, who leads the NHL in saves (238), is now five wins from matching Guy Hebert (173) for second-most in Ducks history.
Auston Matthews, Denis Malgin and Alexander Kerfoot scored for the Maple Leafs, who fell to 4-5-1 on the season. Erik Kallgren made 35 saves.
Toronto led 2-1 after a back-and-forth first period, with Anaheim's special teams struggles again showing up early.
The reigning Hart Trophy winner as league MVP, Matthews put Toronto ahead first with a power-play goal. William Nylander brought the puck down right wing, drawing the Ducks defense towards him before setting up an open Matthews in the slot, where he zipped it past Gibson for his third goal of the season.
Matthews has goals in two of his last three games and appears to be picking up a steam in the season after he became the first NHL player in a decade to score 60 goals in a single campaign.
Nylander, who is now second among team leaders in scoring, has found the scoresheet in eight of his first 10 games this season.
The Ducks have allowed the game's opening goal in seven of nine games this season, and conceded a power-play tally in four consecutive contests.
Anaheim responded on a pretty passing play by Silfverberg and Grant. With the Ducks on the forecheck, Grant got to a loose puck along the goal line, spinning and delivering a no-look pass to Silfverberg in the right faceoff circle. Silfverberg made quick work of the opportunity, quickly burying his bid to the far side before Kallgren could get set in his crease.