The Old Lady have chosen former Italy manager the veteran manager to take the helm for the rest of the term.
The 66-year-old steps in for Igor Tudor, who was let go following the loss to Lazio last weekend.
Tudor arrived at the club in March as Thiago Motta's replacement 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, after the team's failure to reach the 2022 World Cup under former boss Roberto Mancini.
He secured their spot in Euro 2024 exiting in the last 16 stage against Switzerland.
Nonetheless, Italy dismissed Spalletti 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 has also managed Inter Milan, Roma and Udinese in Serie A and lifted the Russian league trophy twice while at 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 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.
