Juventus have named former Italian national team boss the veteran manager to take the helm for the remainder of the campaign.
Spalletti steps in for Igor Tudor, who was let go following the loss to Lazio on Sunday.
The former boss came on board in March filling the shoes of Thiago Motta but exited following a seven-month stint at the end of an eight-match winless run.
Under Spalletti, Napoli clinched the Serie A championship 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.
Under his guidance, they made it to Euro 2024 where they were knocked out in the last 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti 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 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 served as interim manager for 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, having lost once and drawn twice in their opening three matches.