Karlsson cut it to 3-2 at 1:34 of the third period with a backhand near the crease, and Pietrangelo, who played 32:30, tied it 3-3 with his first goal in 10 games at 11:48 during a 5-on-3 power play.
Vegas was without defenseman Shea Theodore, who was placed in NHL COVID-19 protocol before the game.
"I knew I was going to play a lot with some people out," Pietrangelo said. "I thought, collectively as a group, we did a real good job shutting them down. I know they scored three, but we did a pretty good job as a whole."
NOTES: Matthews scored in his eighth straight road game, tying the Maple Leafs record (Daniel Marois, 1989-90; Frank Mahovlich, 1960-61; Babe Dye, 1920-21). … Toronto forward Ondrej Kase had an assist in 20:40 after being unavailable Saturday because of an undisclosed injury. … Vegas forwards Nolan Patrick and Nicolas Roy were also placed in COVID-19 protocol. Forwards Jonas Rondbjerg and Jake Leschyshyn and defenseman Daniil Miromanov were recalled from Henderson of the American Hockey League. … Stephenson had an assist to set an NHL career high with 36 points (10 goals, 26 assists); he scored 35 in 51 games last season.