The Serie A powerhouse have named ex- Italian national team head coach the veteran manager to lead the team for the rest of the term.
The experienced coach steps in for 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 before taking charge of Italy, after the team's failure to reach the 2022 World Cup under former boss Roberto Mancini.
He secured their spot in Euro 2024 where they were knocked out in the last 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June post a qualifying defeat against Norway, putting Italy in danger of missing a third straight World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus during the 3-1 victory over Udinese on Wednesday which left them seventh in Serie A - trailing leaders Napoli by six points after nine matches.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.
