Thompson had his second shutout of the season and third overall to help Western Conference-leading Vegas improve to 7-2-0. Karlsson had his third multi-point game of the season.
Chandler Stephenson, Reilly Smith and Nic Roy also scored. Vegas has scored at least four goals five times, while it has allowed two or fewer goals six times.
''That's a team win, right? They're making my job really easy,'' Thompson said. ''I can't credit the guys enough for blocking everything and just making my life pretty easy out there. Since the start of the season I think you've seen how good we've been defensively, I think it's pretty evident.
''We don't usually give up high-danger scoring chances and I think that's the case tonight. Yeah, 29 shots, but I think they were all from the outside, I was able to get my sticks on it and hand on it. Credit to the team and the system, it's been killing it all year so far.''
To Thompson's point, the Golden Knights outdistanced Anaheim in high-danger chances, 12-7, per NaturalStatTrick.com.
''I think that's an identity we want, we want that to be our reputation around the league, that hey these guys, when we come into the Fortress, you're not getting much - and then anywhere we play for that matter - all of a sudden it can really help your offensive game,'' Vegas coach Bruce Cassidy said. ''We have good offensive players, I think that's the most important thing. ... When the puck's on our stick with time and space we can make some plays and finish.
Anaheim goaltender John Gibson made 14 saves in two periods, and Anthony Stolarz stopped three shots in the third. Gibson has 15 losses to the Knights, six more than any other goaltender. Vegas is 21-4-0 against Anaheim.
Since a 5-4 overtime victory over Seattle in the opener, the Ducks have lost seven straight to drop to 1-6-1.
''We talked about their starts, I think in four or five games this year they had scored the first goal in the first five minutes of the game,'' Anaheim coach Dallas Eakins said. ''The start of the game I thought was fine until we decided to turn a couple of pucks over. When you do that, heart rates are high, you're into a long shift, and that's when they get their action. I thought the first part of it we managed it well `til we made a couple of mental mistakes, which just feeds into a veteran team like that.''
With Anaheim's Ryan Strome in the penalty box for a shot to Mark Stone after referees stepped in to break up a scrum, Stephenson skated across the crease and slipped the puck through Gibson's pads to put Vegas in front 1-0 late in the first period.
Shortly after several heated exchanges midway through the second, and Vegas skating short-handed, Karlsson skated down the left side before sending a perfect pass to a trailing Smith, who beat Gibson with a one-timer to notch his 100th goal as a member of the Golden Knights.
Later in the period, it was Karlsson with the nifty redirect after linemate Jonathan Marchessault skated the puck to the top of the right circle and fired a shot toward Gibson. Karlsson's deflection beat Gibson over his glove, and Roy put it out of reach with less than a minute left in the second period, when he raced in untouched.
For Karlsson, it's been a bit of a coming out party, with four goals and three assists in the first nine games - the fastest start of his career.
''Last year, I wasn't happy with my performance so I wanted to go out and prove to myself that I could be a good hockey player,'' Karlsson ''Two ingredients when you're playing hockey, confidence and having fun, that's when you play your best.''
NOTES: Golden Knights forward Phil Kessel was honored before the opening puck drop with a video tribute to commemorate his record-breaking 990th consecutive game Tuesday night in San Jose. Karlsson is the Golden Knight with next longest active streak, behind Kessel's 991, at 68 games. ... After being checked into the boards by Vegas' William Carrier in the second period, Ducks defenseman Jamie Drysdale left the game and did not return. ... Ducks forward Jakob Silfverberg surpassed Steve Rucchin for fifth on the club's all-time games played list with 617.
Anaheim: Hosts Toronto on Sunday
Vegas: Hosts Winnipeg on Sunday
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