Fleury, who leads the NHL with 19 wins, is tied with Tony Esposito (423) on the all-time list.
Vegas, which has won 10 of its past 14 games (10-3-1), will be without forward Max Pacioretty (undisclosed) for at least the next three games.
The Islanders will try to win their fourth straight game. Barry Trotz returns to Las Vegas for the first time since winning the Stanley Cup as coach of the Washington Capitals in Game 5 of the Final last season.
Defenseman Luca Sbisa, who was selected by Vegas in the 2017 NHL Expansion Draft from the Vancouver Canucks, faces the Golden Knights for the first time since he signed a one-year contract with the Islanders on Sept. 24. Sbisa had 14 points (two goals, 12 assists) in 30 regular-season games last season.