The Old Lady have named former Italian national team head coach Spalletti to take the helm until the end of the season.
The 66-year-old replaces Igor Tudor, who was let go after the Serie A side's defeat by Lazio on Sunday.
Tudor had joined the club in March filling the shoes of Thiago Motta but exited following a seven-month stint at the end of an eight-match winless run.
Spalletti led Napoli to the Serie A title 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 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June after a World Cup qualifying defeat by Norway, as Italy faced the possibility of not making a third World Cup in a row.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A 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 moving them to seventh position in the league - 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.
