William Nylander scored twice, and Joseph Woll made 28 saves for the Maple Leafs (21-11-2), who had won three in a row and five of six.
Toronto was without forward Auston Matthews, who did not play because of an upper-body injury following a 6-3 win against the Buffalo Sabres on Friday. Matthews missed nine games with a related injury in November.
The Maple Leafs are 42-22-2 all time without Matthews since he entered the League in 2016-17.
“We need everybody to step up,” Toronto coach Craig Berube said. “We didn’t have enough guys step up tonight and do the job.”
Maxim Tsyplakov put the Islanders up 1-0 at 1:47 of the first period when he one-touched a pass in the slot from Horvat, who was behind the net, past Woll’s blocker.
Horvat made it 2-0 at 4:48 after he carried the puck into the zone on a 2-on-1 with Simon Holmstrom and scored blocker side from the right face-off dot.
Berube then called a timeout for the Maple Leafs, who were playing the second of back-to-back games facing an Islanders team that had not played since a 4-0 loss to the Carolina Hurricanes on Tuesday.
“You’re on a back-to-back, fresh team waiting for you who hasn’t played in a while and we give up two 2-on-1s in the first five minutes of the game,” Berube said. “That’s how I see it, just not very smart. A little (surprising). Early on in the period, they were better than us, on their toes and we weren’t very smart.
“I get they’re rested and they’re going to be a little more quicker, but we have to be smarter than that. You can’t give the freebees, and we gave them two right away and got behind. Wasn’t a good game.”
Nylander cut it to 2-1 at 12:29 when he skated from just inside the blue line and backhanded a shot over Sorokin’s glove from just outside the left hashmarks.
Jean-Gabriel Pageau extended it to 3-1 at 16:08, putting in a rebound after Woll made a pad save on Anders Lee.
“They came out with real good pace and purpose to their game,” Maple Leafs forward John Tavares said. “On nights where your legs are a little slow to get going, we have to do a better job on how we manage that and not put ourselves in that position after one period.”
Nylander made it 3-2 at 5:43 with his second goal of the game when he put in a backhand pass from David Kampf at the top of the goal crease while being knocked down by Ryan Pulock. It was his fifth goal during a three-game streak.
George pushed it to 4-2 at 5:23 of the third period. He took a pass from Duclair and shot glove side from the top of the left circle.
“Pretty much every NHL game I’ve been to has been in this rink, so it was really cool to be able to play here,” said George, who grew up in Oakville, Ontario, about a 40-minute drive west of Toronto. “Definitely for sure (I envisioned myself) scoring.”