Juventus have appointed previous Italian national team manager the veteran manager to lead the team until the end of the season.
The experienced coach takes over from Igor Tudor, who was sacked following the loss to Lazio on Sunday.
Tudor arrived at the club in March as Thiago Motta's replacement but exited following a seven-month stint at the end of an eight-match winless run.
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.
He secured their spot in Euro 2024 exiting in the last 16 stage against Switzerland.
Nonetheless, Italy dismissed Spalletti in June after a World Cup qualifying defeat by Norway, putting Italy in danger of missing a third straight World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus in the midweek 3-1 triumph over Udinese placing them seventh in the Serie A standings - six points behind leaders Napoli after nine games.
Their Champions League campaign sees them in 25th place in the group stage, with one loss and two draws in their first three games.