The Serie A powerhouse have named ex- Azzurri boss the veteran manager to take the helm until the end of the season.
The 66-year-old steps in for Igor Tudor, who was dismissed after the Serie A side's defeat by Lazio last weekend.
Tudor arrived at the club in March as Thiago Motta's replacement but departed after seven months at the end of an eight-match winless run.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, who had failed to qualify for 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.
Nonetheless, Italy dismissed Spalletti in June following a loss to Norway in World Cup qualifying, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and won the Russian Premier League twice 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.
