The Serie A powerhouse have chosen previous Italian national team boss the veteran manager as their manager for the remainder of the campaign.
Spalletti takes over from Igor Tudor, who was dismissed following the loss to Lazio recently.
Tudor arrived at the club in March to replace Thiago Motta but left after seven months after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, 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.
However, Spalletti was sacked by Italy in June following a loss to Norway in World Cup qualifying, as Italy faced the possibility of not making a third World Cup in a row.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and won the Russian Premier League twice with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla during the 3-1 victory over Udinese on Wednesday which left them seventh in Serie A - trailing leaders Napoli by six points after nine matches.
Their Champions League campaign sees them in 25th place in the group stage, having lost once and drawn twice in their opening three matches.