Juventus have chosen previous Azzurri boss the veteran manager to take the helm for the rest of the term.
Spalletti steps in for Igor Tudor, who was dismissed post the Lazio setback on Sunday.
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 guided Napoli to the Serie A crown 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.
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 has also managed 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 which left them seventh in Serie A - six points adrift of Napoli at the top after nine rounds.
In the Champions League, they sit 25th in the league phase, after recording one defeat and two ties in the initial three fixtures.