Juventus have chosen previous Italian national team head coach the veteran manager to take the helm until the end of the season.
The 66-year-old takes over from Igor Tudor, who was let go after the Serie A side's defeat by Lazio on Sunday.
The former boss came on board in March filling the shoes of Thiago Motta but exited following a seven-month stint following a string of eight matches without a victory.
Spalletti led Napoli to the Serie A title 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 helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go 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 won the Russian Premier League twice 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 - six points adrift of Napoli at the top after nine rounds.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.