On 21 June 2017, having been left "exposed" by Columbus for the 2017 NHL Expansion Draft, Karlsson was selected by the expansion Vegas Golden Knights. Karlsson spent the 2017-18 season (Vegas' first in the NHL) centering a line with Reilly Smith and Jonathan Marchessault. This proved to be a productive line, with all three putting up career-high offensive numbers. Karlsson scored his first career NHL hat-trick on 31 December 2017 against the Toronto Maple Leafs, it also being the first hat-trick in Golden Knights history. In addition to providing 35 assists and an NHL-high plus-minus rating of +45, Karlsson ended the regular season with 43 goals, setting a new NHL record for goals scored by a player in an expansion team's inaugural season. His 43 goals placed him third in NHL scoring, behind Patrik Laine (44) and Alexander Ovechkin (49). Karlsson was also named a finalist for the Lady Byng Memorial Trophy for his high standard of play and sportsmanship. On 20 June, he was named the recipient of the trophy, becoming the first player since Wayne Gretzky to win an end-of-season award in their team's inaugural season in the NHL.
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