Juventus have appointed former Azzurri boss the veteran manager to take the helm for the remainder of the campaign.
Spalletti takes over from Igor Tudor, who was sacked following the loss to Lazio on Sunday.
Tudor had joined the club in March as Thiago Motta's replacement but left after seven months following a string of eight matches without a victory.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 where they were knocked out in the last 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti 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.
Massimo Brambilla served as interim manager for Juventus 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.
In the Champions League, they sit 25th in the league phase, with one loss and two draws in their first three games.