Karlsson extended the lead to 3-0 when he tipped Jonathan Marchessault's right point shot at 14:26.
"It's just me going to the front of the net," Karlsson said. "That's where I feel like 90-95 percent of goals are scored. Better there than the corners."
Nicolas Roy pushed it to 4-0 at 18:47 when he got to a bouncing puck behind the defense and chipped it in.
"We have good offensive players," Cassidy said. "We're not a high-volume team. When the puck is on our stick and we have time and space, we can make some plays and finish. Tonight was a good example. We didn't dominate the shot clock by any means, even some left on the table."
Anaheim defenseman Jamie Drysdale left the game midway through the second with an upper-body injury. There was no update on him after the game.
"Unfortunately, Jamie goes down," Eakins said. "But thankfully, we had seven [defensemen] dressed."
NOTES: Jakob Silfverberg played his 617th game with the Ducks, passing Steve Rucchin for fifth in franchise history. … Stephenson has a five-game point streak (four goals, one assist), matching the longest of his NHL career. … Smith scored his 100th goal with the Golden Knights (330 games).