The Serie A powerhouse have named former Italy boss the veteran manager to take the helm until the end of the season.
The 66-year-old takes over from the Croatian manager, who was dismissed post the Lazio setback last weekend.
The former boss came on board 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 before taking charge of Italy, who had failed to qualify for the 2022 World Cup during Roberto Mancini's tenure.
He helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against 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 won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus in the midweek 3-1 triumph over Udinese 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.
