Juventus have named ex- Azzurri manager the veteran manager to take the helm for the rest of the term.
The experienced coach takes over from the Croatian manager, who was dismissed post the Lazio setback recently.
The former boss came on board in March filling the shoes of Thiago Motta but left after seven months following a string of eight matches without a victory.
Spalletti led Napoli to the Serie A title in 2022-23 then moving on to lead the Italian national team, which missed out on the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 exiting in the last 16 stage against 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 secured two Russian Premier League titles with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla in the midweek 3-1 triumph over Udinese which left them seventh in Serie A - six points adrift of Napoli at the top after nine rounds.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.
