Juventus have appointed ex- Italy boss the veteran manager as their manager until the end of the season.
The 66-year-old replaces his predecessor, who was dismissed following the loss to Lazio recently.
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.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, who had failed to qualify for 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.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti's managerial career includes 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 placing them seventh in the Serie A standings - six points adrift of Napoli at the top after nine rounds.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.
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