The Old Lady have chosen former Italian national team head coach Spalletti to lead the team until the end of the season.
The experienced coach takes over from his predecessor, who was let go after the Serie A side's defeat by Lazio last weekend.
The former boss came on board in March as Thiago Motta's replacement but departed after seven months after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown in 2022-23 prior to assuming the Italy role, 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.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, 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 lifted the Russian league trophy twice while at Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla for their 3-1 win against Udinese on Wednesday placing them seventh in the Serie A standings - 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.
