The Old Lady have chosen ex- Italian national team boss the veteran manager to lead the team until the end of the season.
Spalletti steps in for Igor Tudor, who was sacked following the loss to Lazio last weekend.
Tudor arrived at the club in March filling the shoes of Thiago Motta 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, who had failed to qualify for the 2022 World Cup during Roberto Mancini's tenure.
He helped them qualify for Euro 2024 exiting in the last 16 stage against Switzerland.
Nonetheless, Italy dismissed Spalletti in June post a qualifying defeat against 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 lifted the Russian league trophy twice while at 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.
In the Champions League, they sit 25th in the league phase, with one loss and two draws in their first three games.
