The Serie A powerhouse have appointed ex- Italian national team manager the veteran manager to take the helm for the remainder of the campaign.
The 66-year-old takes over from Igor Tudor, who was let go following the loss to Lazio last weekend.
Tudor arrived at the club in March filling the shoes of Thiago Motta but left after seven months after an eight-game winless streak.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 exiting in the last 16 stage against Switzerland.
Nonetheless, Italy dismissed Spalletti in June following a loss to Norway in World Cup qualifying, 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.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against 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, with one loss and two draws in their first three games.
