The Serie A powerhouse have named ex- Azzurri boss Spalletti to lead the team until the end of the season.
Spalletti steps in for his predecessor, who was sacked after the Serie A side's defeat by Lazio last weekend.
The former boss came on board in March filling the shoes of Thiago Motta but exited following a seven-month stint at the end of an eight-match winless run.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, who had failed to qualify for 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.
However, Spalletti was sacked by Italy in June following a loss to Norway in World Cup qualifying, putting Italy in danger of missing a third straight World Cup.
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.
Their Champions League campaign sees them in 25th place in the group stage, after recording one defeat and two ties in the initial three fixtures.
