Juventus have appointed previous Italian national team 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 following the loss to Lazio on Sunday.
Tudor had joined the club in March to replace Thiago Motta but exited following a seven-month stint after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown in 2022-23 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to 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.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus for their 3-1 win against Udinese on Wednesday placing them seventh in the Serie A standings - trailing leaders Napoli by six points after nine matches.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.