The Old Lady have named previous Italian national team boss the veteran manager to lead the team for the remainder of the campaign.
The 66-year-old replaces Igor Tudor, who was dismissed following the loss to Lazio last weekend.
Tudor had joined 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, who had failed to qualify for the 2022 World Cup during Roberto Mancini's tenure.
He helped them qualify for 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, with the Azzurri at risk of missing out on a third consecutive 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 in the midweek 3-1 triumph over Udinese which left them seventh in Serie A - six points behind leaders Napoli after nine games.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.
