The Serie A powerhouse have appointed ex- Italian national team manager the veteran manager to take the helm for the rest of the term.
The 66-year-old takes over from the Croatian manager, who was let go post the Lazio setback last weekend.
The former boss came on board in March to replace Thiago Motta but departed after seven months 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, 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, as Italy faced the possibility of not making a third World Cup in a row.
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 served as interim manager for Juventus in the midweek 3-1 triumph over Udinese placing them seventh in the Serie A standings - six points adrift of Napoli at the top after nine rounds.
Their Champions League campaign sees them in 25th place in the group stage, having lost once and drawn twice in their opening three matches.
