The Old Lady have named ex- Italian national team head coach Spalletti to lead the team until the end of the season.
Spalletti steps in for Igor Tudor, who was dismissed following the loss to Lazio recently.
The former boss came on board in March to replace Thiago Motta but left after seven months at the end of an eight-match winless run.
Spalletti led Napoli to the Serie A title in 2022-23 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
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, 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 moving them to seventh position in the league - six points adrift of Napoli at the top after nine rounds.
They are 25th in the league phase of the Champions League, after recording one defeat and two ties in the initial three fixtures.