The Serie A powerhouse have appointed ex- Italian national team manager the veteran manager as their manager for the rest of the term.
The experienced coach takes over from the Croatian manager, who was let go following the loss to Lazio on Sunday.
The former boss came on board in March to replace Thiago Motta but exited following a seven-month stint following a string of eight matches without a victory.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, after the team's failure to reach the 2022 World Cup during Roberto Mancini's tenure.
He helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June after a World Cup qualifying defeat by 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 for their 3-1 win against Udinese on Wednesday moving them to seventh position in the league - six points behind leaders Napoli after nine games.
They are 25th in the league phase of the Champions League, after recording one defeat and two ties in the initial three fixtures.
