The Old Lady have named ex- Italian national team boss the veteran manager as their manager for the remainder of the campaign.
The 66-year-old steps in for Igor Tudor, who was let go following the loss to Lazio last weekend.
Tudor had joined the club in March to replace Thiago Motta but departed after seven months following a string of eight matches without a victory.
Spalletti guided Napoli to the Serie A crown in 2022-23 then moving on to lead the Italian national team, 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 but were eliminated in the round of 16 by Switzerland.
However, Spalletti was sacked by Italy in June following a loss to Norway in World Cup qualifying, with the Azzurri at risk of missing out on a third consecutive World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and secured two Russian Premier League titles with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla for their 3-1 win against Udinese on Wednesday moving them to seventh position in the league - six points behind leaders Napoli after nine games.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.