The Old Lady have appointed previous Italy manager the veteran manager to take the helm for the rest of the term.
Spalletti replaces the Croatian manager, who was let go following the loss to Lazio last weekend.
The former boss came on board in March filling the shoes of Thiago Motta but exited following a seven-month stint following a string of eight matches without a victory.
Spalletti led Napoli to the Serie A title in 2022-23 before taking charge of Italy, after the team's failure to reach the 2022 World Cup with Mancini at the helm.
He secured their spot in 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 secured two Russian Premier League titles with 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.
They are 25th in the league phase of the Champions League, having lost once and drawn twice in their opening three matches.