The Serie A powerhouse have appointed former Italian national team head coach Spalletti to take the helm for the remainder of the campaign.
Spalletti takes over from Igor Tudor, who was dismissed post the Lazio setback last weekend.
Tudor had joined the club in March filling the shoes of Thiago Motta but exited following a seven-month stint 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 secured their spot in Euro 2024 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June following a loss to Norway in World Cup qualifying, putting Italy in danger of missing a third straight 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 took interim charge of Juventus during the 3-1 victory over Udinese on Wednesday moving them to seventh position in the league - trailing leaders Napoli by six points after nine matches.
They are 25th in the league phase of the Champions League, having lost once and drawn twice in their opening three matches.
