Comeau settled a pass from Kris Letang and fired a shot from the point for his third goal of the night and eighth of the season. Evgeni Malkin added a goal and two assists, and Sidney Crosby had two assists to become the third player in Penguins history to reach 800 points.
Marc-Andre Fleury, wearing gold pads for the first time in seven years, stopped 24 shots for his 301st win.
Leo Komarov scored twice for the Maple Leafs, and Tyler Bozak got his ninth of the season. Bernier made 22 saves but couldn't get a hand on Comeau's winner.
The Penguins improved to 11-0-3 in their last 14 games against Canadian teams and beat the Maple Leafs for the fifth straight time.
Comeau gave the Penguins the lead just 26 seconds in, banging home a backhand past Bernier while getting checked to his knees. The forward's sixth goal of the season marked the 17th time in 21 games Pittsburgh has scored first.
Malkin made it 2-0 at 12:39 of the period, leaning into a soft drop pass from Letang and sending a scorching one-timer by a well-screened Bernier for his 11th goal and fourth in the last three games. Crosby picked up the secondary assist to lift his career point total to 799.
The Maple Leafs steadied themselves in the second behind an unlikely surge from Komarov. The Russian-born forward came in with just six goals in 63 career games but picked up two in less than three minutes to tie it. He finished a 3-on-2 break by burying a feed from Mike Santorelli to make it 2-1 and then evened the score with a nifty deflection of Dion Phaneuf's shot from outside the left circle.
Comeau got a piece of Chris Kunitz's flip from the left half-boards to put Pittsburgh back in front, but a giveaway by Crosby led to a breakout for Bozak, who outraced Letang and beat Fleury to tie it once again. The short-handed goal was the fourth allowed by the Penguins this season, tied for most in the NHL.
Pittsburgh had several chances to win in regulation, including a frantic scramble in front of the Toronto net in the final minute that Bernier spent on his stomach looking for the puck. He managed to help the Maple Leafs earn a point by sending the game to an extra session, but the Penguins dominated overtime before Comeau bookended his hot start with a dazzling finish.
NOTES: Penguins F Beau Bennett is out for a couple of weeks with a lower-body injury. Bennett appeared to hurt his right knee after colliding with Boston's Kevan Miller on Monday night. ... Toronto scratched D Roman Polak, who is out four weeks with a knee injury sustained last weekend. ... The Maple Leafs wore a green clover with the initials "P.Q." on it to honor former coach Pat Quinn, who died Sunday at age 71. Quinn won 300 games while coaching Toronto from 1998-2006. ... Pittsburgh hosts Carolina on Friday. Toronto hosts Washington on Saturday.