The Old Lady have chosen previous Italian national team head coach the veteran manager to take the helm until the end of the season.
Spalletti takes over from 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 exited following a seven-month stint after an eight-game winless streak.
Spalletti led Napoli to the Serie A title in 2022-23 then moving on to lead the Italian national team, after the team's failure to reach the 2022 World Cup with Mancini at the helm.
He helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June post a qualifying defeat against Norway, putting Italy in danger of missing a third straight World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against Udinese on Wednesday placing them seventh in the Serie A standings - trailing leaders Napoli by six points after nine matches.
They are 25th in the league phase of the Champions League, having lost once and drawn twice in their opening three matches.
