John Gibson made a season-high 47 saves for the Ducks (14-24-7), who were trying to win three straight games for the first time this season.
"This was a tough game for us," Anaheim forward Jakob Silfverberg said. "We were coming off two good games [at the San Jose Sharks] and feeling pretty good about our game, but tonight is definitely a step in the wrong direction."
The teams will play again here Sunday.
After failing to score despite outshooting Anaheim 15-6 in the first period, including 11-1 in the opening 10:12, Vegas scored three times in the second period, when it had a 23-3 advantage in shots on goal.
"They're pushing the pace out there," Silfverberg said. "They're making plays, they're stretching guys, making it hard for us. They're spreading us out, bumping pucks back. It's tough."
William Karlsson made it 1-0 nine seconds into the period. He won the opening face-off, and Reilly Smith drove to the net against rookie defenseman Jamie Drysdale. Gibson made the save against Smith from in close, but Karlsson scored on the rebound.
"Let's just say everyone knew what they were doing," Karlsson said of the set play to open the period.