The Serie A powerhouse have named ex- Italy head coach the veteran manager as their manager for the remainder of the campaign.
Spalletti replaces Igor Tudor, who was dismissed post the Lazio setback on Sunday.
Tudor arrived at the club in March to replace Thiago Motta but departed after seven months after an eight-game winless streak.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, who had failed to qualify for the 2022 World Cup during Roberto Mancini's tenure.
Under his guidance, they made it to Euro 2024 but were eliminated in the round of 16 by Switzerland.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, putting Italy in danger of missing a third straight World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus in the midweek 3-1 triumph over Udinese which left them seventh in Serie A - six points behind leaders Napoli after nine games.
In the Champions League, they sit 25th in the league phase, after recording one defeat and two ties in the initial three fixtures.
