The Old Lady have appointed previous Italian national team manager Spalletti to take the helm until the end of the season.
The experienced coach replaces Igor Tudor, who was sacked after the Serie A side's defeat by Lazio on Sunday.
Tudor had joined the club in March as Thiago Motta's replacement but departed after seven months following a string of eight matches without a victory.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, which missed out on the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 where they were knocked out in the last 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June following a loss to Norway in World Cup qualifying, as Italy faced the possibility of not making a third World Cup in a row.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and secured two Russian Premier League titles with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla for their 3-1 win against Udinese on Wednesday which left them seventh in Serie A - six points adrift of Napoli at the top after nine rounds.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.
