The Old Lady have appointed ex- Azzurri manager the veteran manager to take the helm for the rest of the term.
The 66-year-old takes over from Igor Tudor, who was dismissed following the loss to Lazio recently.
Tudor had joined the club in March filling the shoes of 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.
He helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus during the 3-1 victory over 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.
