The Old Lady have appointed former Italy manager Spalletti to take the helm until the end of the season.
The 66-year-old steps in for Igor Tudor, who was dismissed after the Serie A side's defeat by Lazio last weekend.
Tudor had joined the club in March to replace Thiago Motta but left after seven months after an eight-game winless streak.
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 where they were knocked out in the last 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June after a World Cup qualifying defeat by Norway, 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 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 - six points behind leaders Napoli after nine games.
They are 25th in the league phase of the Champions League, having lost once and drawn twice in their opening three matches.
