Juventus have appointed ex- Italy head coach the veteran manager to take the helm for the remainder of the campaign.
The 66-year-old takes over from Igor Tudor, who was let go after the Serie A side's defeat by Lazio recently.
The former boss came on board in March to replace Thiago Motta but left after seven months after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown in 2022-23 prior to assuming the Italy role, after the team's failure to reach the 2022 World Cup with Mancini at the helm.
He secured their spot in 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 has also managed Inter Milan, Roma and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus during the 3-1 victory over Udinese on Wednesday moving them to seventh position in the league - trailing leaders Napoli by six points after nine matches.
Their Champions League campaign sees them in 25th place in the group stage, with one loss and two draws in their first three games.