Juventus have chosen previous Italian national team manager the veteran manager as their manager for the rest of the term.
The 66-year-old steps in for Igor Tudor, who was sacked post the Lazio setback on Sunday.
Tudor arrived at the club in March to replace Thiago Motta but left after seven months following a string of eight matches without a victory.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 before taking charge of Italy, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June following a loss to Norway in World Cup qualifying, putting Italy in danger of missing a third straight 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 took interim charge of Juventus during the 3-1 victory over 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.