The 19-year-old from Scottsdale, Arizona, chosen first overall in June's NHL draft, scored on his first three shots against the Senators, with the hat trick prompting visiting Leafs fans at the Canadian Tire Center in Ottawa to throw hats onto the ice.
Three was not enough, however.
Matthews took a pass from linemate William Nylander on a 2-on-1 break and scored a fourth goal (on just his sixth shot) with three seconds left in the second period, becoming the first player in modern NHL history to score that many in his debut.
The Senators went on to win the NHL season opener 5-4 in overtime.
Matthews called the night "pretty unbelievable."
"You don't really draw it up like that," he told Sportsnet after the game.
It was a record-breaking evening all around for Matthews.
The hat trick was the quickest for a player making his NHL debut (since 1943-44). And he became the fifth player overall to notch a hat trick in his first game, joining Derek Stepan of the New York Rangers (2010), Fabian Brunnstrom of the Dallas Stars (2008), Real Cloutier of the Quebec Nordiques (1979) and Alex Smart of the Montreal Canadiens (1943).
Matthews scored on his first shot at 8:21 into the first period, snapping in a pass from Zach Hyman during a scrum around the net.
His second goal came with 5:42 left in the first, after he dangled through a pair of Senators near the blue line. After briefly losing possession, he stole the puck from two-time Norris Trophy winner Erik Karlsson along the boards, then beat goalie Craig Anderson with an odd-angle forehand.
Matthews put Toronto ahead 3-2 with a one-timer from inside the right circle on a feed from Morgan Rielly at 1:25 into the second period.
He then netted historic No. 4 with three seconds left in the second period, breaking a 3-3 tie.
Despite the historic first game, Matthews took responsibility for the loss after failing to pick up Turris coming into the Toronto zone. Turris took in a pass from Mark Stone with Matthews chasing, set himself and fired a shot by Frederik Andersen.
"That last play was 100 percent my fault,'' he said. "We came here to win and we didn't get that done.''
According to Elias Sports Bureau research, Matthews is the third-youngest player with four goals in a game, surpassed only by 18-year-olds Jack Hamilton (1943-44) and Bob Carpenter (1981-82).
And at his current pace, Matthews will break Wayne Gretzky's NHL record of 894 goals in late February 2019, during his third NHL season and his 224th NHL game. (Gretzky had 186 goals in his first 224 NHL games.)
After Wednesday night's game, however, Matthews downplayed any notion of ratcheted-up expectations.
"You don't get too many of those games," said Matthews, the 12th first overall pick to score in his NHL debut. "It's just one game. Take it, move forward and focus on the next one. It just happened to be a great night individually, and especially for our line."
His parents, Brian and Ema Matthews, were at the game Wednesday night, and the look on their faces after each goal translated pure emotion.
"It meant a lot," Matthews said of having his parents there. "Pretty special moment, not just for myself but for them, as well. They have been a pretty huge part of getting me to this point, so it was only right for them to be here for the first one."
Matthews Mania no doubt already is sweeping the NHL, but don't be in a rush to buy any of his jerseys just yet.
The NHL's official store does not have any Matthews jerseys ready to go, so if fans want to purchase one, they have to customize it.
The Leafs, who finished 30th overall in the standings in 2015-16, were accused by many of tanking last season in their attempt to secure the best possible odds in the NHL draft lottery to get Matthews. They lost out the previous year in the lottery, with the Edmonton Oilers taking Connor McDavid first overall.
This time, the Leafs won the lottery, and there wasn't any hesitation in making Matthews the first overall pick. He is at the heart of a massive rebuild. The Leafs' Stanley Cup drought dates back to 1967, and the current regime led by president Brendan Shanahan, general manager Lou Lamoriello and coach Mike Babcock is intent on making this youth movement work.
"I thought just for me, from my perspective, since I've been the Leafs coach, that's the best night I've had since I've been here by 10 miles, not even close, because now we have an opportunity," Babcock said after Wednesday night's defeat.
"When you look at [Mitch] Marner -- I know Matthews scored all the goals -- I thought Marner in the first half of the game might have been the best player. I thought Nylander was great. I thought Hyman was great. I thought [Connor] Brown was great. I thought [Sam] Carrick was great. I thought [Nikita] Zaitsev was great. Pretty good night for us. Did we want the other point? Absolutely. The way we controlled the puck and controlled the game, you've got to win, and we didn't."
Matthews arrives with a ton of hype in hockey's biggest market, but he has already shown maturity beyond his years.
"He's a man,'' Babcock said. "He's 19 years old but he acts like he's 27. He has great maturity. If you meet his mom and dad, you're thoroughly impressed with the kind of people they are and the respect he has for his mom and sisters, the kind of guy he is.
"Don't get me wrong, we would've drafted him anyway, but that makes him more special.''
Information from The Associated Press, ESPN Stats & Information and ESPN's Darren Rovell was used in this report.