The Old Lady have chosen previous Italy manager Spalletti to take the helm 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 exited following a seven-month stint following a string of eight matches without a victory.
Spalletti led Napoli to the Serie A title 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 helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
However, Spalletti was sacked by Italy in June post a qualifying defeat against Norway, putting Italy in danger of missing a third straight World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and secured two Russian Premier League titles with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla during the 3-1 victory over Udinese on Wednesday moving them to seventh position in the league - 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.