The Old Lady have named ex- Azzurri head coach Spalletti as their manager until the end of the season.
The 66-year-old steps in for the Croatian manager, who was sacked following the loss to Lazio on Sunday.
The former boss came on board 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 then moving on to lead the Italian national team, which missed out on 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.
Yet, the Italian FA let Spalletti go in June after a World Cup qualifying defeat by Norway, as Italy faced the possibility of not making a third World Cup in a row.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla 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.
In the Champions League, they sit 25th in the league phase, with one loss and two draws in their first three games.