The Serie A powerhouse have named ex- Italian national team manager the veteran manager to take the helm for the rest of the term.
The 66-year-old replaces Igor Tudor, who was let go following the loss to Lazio on Sunday.
Tudor arrived at the club in March as Thiago Motta's replacement but exited following a seven-month stint after an eight-game winless streak.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 then moving on to lead the Italian national team, after the team's failure to reach the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 where they were knocked out in the last 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and won the Russian Premier League twice with 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 - trailing leaders Napoli by six points after nine matches.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.
