The Old Lady have appointed previous Italy boss the veteran manager to lead the team until the end of the season.
The 66-year-old replaces Igor Tudor, who was sacked following the loss to Lazio on Sunday.
The former boss came on board in March to replace Thiago Motta but departed after seven months after an eight-game winless streak.
Spalletti led Napoli to the Serie A title in 2022-23 before taking charge of Italy, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
He helped them qualify for Euro 2024 exiting in the last 16 stage against 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 has also managed 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 for their 3-1 win against Udinese on Wednesday which left them seventh in Serie A - trailing leaders Napoli by six points after nine matches.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.
