Vegas, now riding a 5-1 winning streak after completing a seven-game homestand, improved to 16-2-1 against Pacific Division teams.
Vegas' Marc-Andre Fleury, who is four wins shy of becoming the 13th goalie in NHL history to register 400 career wins, stopped 30 shots.
Vancouver, which dropped to 3-7-1 in February, is 5-11-1 against intradivision foes.
Vegas opened the scoring when Hyka, playing in just his third NHL game, scored his first career goal 2:29 into the game.
The Canucks then displayed a little bit of offensive prowess of their own, tying the game when Sam Gagner's pass slipped under Vegas defenseman Luca Sbisa and Baertschi punched it home, then taking a 2-1 lead when Vanek tapped in a loose puck.
Vegas reclaimed the lead on a pair of Karlsson goals, late in the first period and 5:36 into the second. Karlsson's two goals give him 33 for the season, third-best in the NHL behind Washington's Alex Ovechkin (36) and Pittsburgh's Evgeni Malkin (34).
The Golden Knights extended their lead to 5-2 on Marchessault's 22nd goal of the season, and Tomas Nosek's seventh of the campaign.
Sedin notched his 16th goal of the season, when he beat Fleury top shelf with a power play goal 4:28 into the third period.
Perron scored an empty net goal for the final margin. Along with his assist on Nosek's goal, Perron tied his career-high of 57 points.
Vegas has now scored a power-play goal in 14 of its last 16 games. ... The Golden Knights are 25-3-0 record when scoring the first goal of the game while their .893 win percentage when recording the opening mark leads the NHL. ... Baertschi now has seven points (3 goals, 4 assists) over the past seven games.
Vancouver: At Arizona on Sunday
Vegas: At Los Angeles on Monday