Karlsson made it 3-0 at 7:53 with slap shot on the power play. Nico Sturm scored from the slot eight seconds later to extend the lead to 4-0.
"It's a little bit easier to play when you have the lead early, so that definitely helped," Karlsson said. "Hopefully we can string a few [wins] together and not just have one here and there."
Zegras made it 4-1 at 9:37 of the second on a wrist shot from the left circle, but Nick Bonino shot into an empty net with 3:42 left to make it 5-1.
With Stolarz back in goal, Steven Lorentz scored with 3:17 remaining for the 6-1 final.
"The only way we are going to get out of it is together," Ducks forward Sam Carrick said. "You can't really feel sorry for yourself, this League is too relentless."
NOTES: Makiniemi made his NHL debut in relief of Kaapo Kahkonen in a 6-5 overtime loss to the Vancouver Canucks on Wednesday. ... San Jose goalie James Reimer is expected to return on Tuesday against the visiting Coyotes. He sustained a lower body injury in a 5-2 loss to the Los Angeles Kings on Nov. 25. ... Fowler had an assist on Zegras' goal and has 14 points (three goals, 11 assists) in his past 13 games. ... Gibson has not finished six of his 21 starts this season. ... Ducks defenseman John Klingberg returned after missing the previous seven games with a lower-body injury. He had three hits in 20:52. ... Anaheim forward Jayson Megna played 9:27 in his Ducks debut after he was claimed off waivers from the Colorado Avalanche on Tuesday. Megna was also playing his first NHL game against his younger brother, Jaycob, a defenseman for the Sharks.