The Golden Knights own the top home record in the league, moving to 18-2-1 in the first 21 contests at T-Mobile Arena. Vegas is 9-0-1 in its last 10 at home, including seven straight wins.
Behind excellent puck movement on the game-winner, defenseman Deryk Engelland found Jonathan Marchessault with a blueline-to-blueline pass. Marchessault then pushed the puck forward to Reilly Smith, who found Karlsson at the right dot for a one-timer for his team-high 22nd of the season.
Mika Zibanejad scored for the Rangers and Ondrej Pavelec, making his 10th appearance of the season, finished with 32 saves.
Since the start of last season, New York is 14-7-0 in the second game of a back-to-back set. The Rangers, who lead the NHL in road wins since the start of last season with 34, were coming off a shootout victory at Arizona on Saturday night, when Henrik Lundqvist stopped 38 of 39 shots he faced in regulation and overtime and all three attempts in the shootout.
New York got on the board first when Zibanejad got his 13th of the season with a wrist shot that beat Fleury on the glove side.
Less than four minutes later, Neal capitlized on a turnover in the attacking zone, to the right of Pavelec, beating him top shelf with a wrist shot that tied the score.
NOTES: Rangers C Mats Zuccarello is just one assist away from 200 in his NHL career. … Engelland remains one point away from 100. … Karlsson leads Vegas with 22 goals, Marchessault is tops with 40 points and tied with David Perron with a team-high 24 assists.
New York: Hosts the New York Islanders on Saturday.
Vegas: Hosts Edmonton on Saturday night.