Juventus have chosen former Azzurri boss the veteran manager as their manager for the remainder of the campaign.
The experienced coach takes over from Igor Tudor, who was dismissed after the Serie A side's defeat by Lazio on Sunday.
The former boss came on board in March as Thiago Motta's replacement 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 then moving on to lead the Italian national team, which missed out on the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 but were eliminated in the round of 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June following a loss to Norway in World Cup qualifying, with the Azzurri at risk of missing out on a third consecutive 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 served as interim manager for 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.
In the Champions League, they sit 25th in the league phase, after recording one defeat and two ties in the initial three fixtures.