Juventus have named previous Azzurri manager the veteran manager to lead the team for the remainder of the campaign.
The experienced coach steps in for his predecessor, who was let go 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 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 prior to assuming the Italy role, who had failed to qualify for 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 has also managed 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 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, having lost once and drawn twice in their opening three matches.