The Serie A powerhouse have chosen previous Italian national team manager Spalletti to take the helm until the end of the season.
Spalletti steps in for his predecessor, who was dismissed post the Lazio setback on Sunday.
The former boss came on board in March as Thiago Motta's replacement but left after seven months after an eight-game winless streak.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, who had failed to qualify for the 2022 World Cup during Roberto Mancini's tenure.
He helped them qualify for Euro 2024 where they were knocked out in the last 16 by Switzerland.
However, Spalletti was sacked by Italy in June post a qualifying defeat against Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus for their 3-1 win against Udinese on Wednesday 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, after recording one defeat and two ties in the initial three fixtures.
