The Old Lady have named ex- Italy manager the veteran manager to take the helm until the end of the season.
The 66-year-old steps in for the Croatian manager, who was sacked after the Serie A side's defeat by Lazio on Sunday.
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 led Napoli to the Serie A title in 2022-23 then moving on to lead the Italian national team, who had failed to qualify for 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.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, putting Italy in danger of missing a third straight 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 in the midweek 3-1 triumph over Udinese 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.
