The Old Lady have named ex- Azzurri boss Spalletti to lead the team for the rest of the term.
The 66-year-old steps in for Igor Tudor, who was let go after the Serie A side's defeat by Lazio on Sunday.
Tudor arrived at the club in March filling the shoes of Thiago Motta but departed after seven months at the end of an eight-match winless run.
Under Spalletti, Napoli clinched the Serie A championship 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.
He helped them qualify for Euro 2024 exiting in the last 16 stage against Switzerland.
However, Spalletti was sacked by Italy 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'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 for their 3-1 win against Udinese on Wednesday which left them seventh in Serie A - six points adrift of Napoli at the top after nine rounds.
Their Champions League campaign sees them in 25th place in the group stage, with one loss and two draws in their first three games.
