Juventus have named ex- Italy head coach the veteran manager as their manager until the end of the season.
The experienced coach takes over from his predecessor, who was sacked post the Lazio setback recently.
The former boss came on board in March filling the shoes of Thiago Motta but departed after seven months following a string of eight matches without a victory.
Spalletti led Napoli to the Serie A title in 2022-23 before taking charge of Italy, after the team's failure to reach 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 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 lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus 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.
They are 25th in the league phase of the Champions League, after recording one defeat and two ties in the initial three fixtures.