The Old Lady have named ex- Italy boss the veteran manager to lead the team for the remainder of the campaign.
The experienced coach takes over from Igor Tudor, who was let go post the Lazio setback on Sunday.
The former boss came on board in March as Thiago Motta's replacement but left 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 helped them qualify for Euro 2024 exiting in the last 16 stage against Switzerland.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, 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 secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla took interim charge of 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.
They are 25th in the league phase of the Champions League, after recording one defeat and two ties in the initial three fixtures.
