The Serie A powerhouse have appointed ex- Azzurri manager Spalletti to lead the team until the end of the season.
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 filling the shoes of Thiago Motta but departed after seven months 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, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
He helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, as Italy faced the possibility of not making a third World Cup in a row.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight 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 placing them seventh in the Serie A standings - six points adrift of Napoli at the top after nine rounds.
Their Champions League campaign sees them in 25th place in the group stage, having lost once and drawn twice in their opening three matches.
