The Old Lady have named previous Italian national team manager the veteran manager as their manager until the end of the season.
The experienced coach takes over from Igor Tudor, who was sacked following the loss to Lazio recently.
The former boss came on board in March filling the shoes of Thiago Motta but exited following a seven-month stint 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, 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 exiting in the last 16 stage against 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.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus during the 3-1 victory over Udinese on Wednesday moving them to seventh position in the league - six points adrift of Napoli at the top after nine rounds.
Their Champions League campaign sees them in 25th place in the group stage, after recording one defeat and two ties in the initial three fixtures.
