The Old Lady have appointed ex- Azzurri head coach the veteran manager to take the helm until the end of the season.
The experienced coach takes over from Igor Tudor, who was sacked post the Lazio setback recently.
Tudor arrived at the club in March as Thiago Motta's replacement but departed after seven months at the end of an eight-match winless run.
Spalletti guided Napoli to the Serie A crown 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.
He helped them qualify for Euro 2024 where they were knocked out in the last 16 by Switzerland.
However, Spalletti was sacked by Italy in June post a qualifying defeat against Norway, 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.
Juventus were temporarily led by Massimo Brambilla 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.
Their Champions League campaign sees them in 25th place in the group stage, having lost once and drawn twice in their opening three matches.
