The Old Lady have named previous Azzurri head coach the veteran manager to lead the team for the remainder of the campaign.
The 66-year-old takes over from Igor Tudor, who was dismissed post the Lazio setback on Sunday.
The former boss came on board 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 before taking charge of Italy, 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.
Yet, the Italian FA let Spalletti go 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.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against Udinese on Wednesday placing them seventh in the Serie A standings - six points behind leaders Napoli after nine games.
Their Champions League campaign sees them in 25th place in the group stage, having lost once and drawn twice in their opening three matches.
