The Old Lady have chosen ex- Azzurri head coach Spalletti to lead the team until the end of the season.
Spalletti replaces the Croatian manager, who was sacked following the loss to Lazio recently.
The former boss came on board in March filling the shoes of Thiago Motta but left after seven months at the end of an eight-match winless run.
Spalletti led Napoli to the Serie A title in 2022-23 prior to assuming the Italy role, who had failed to qualify for 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.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, putting Italy in danger of missing a third straight World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus during the 3-1 victory over Udinese on Wednesday which left them seventh in Serie A - six points behind leaders Napoli after nine games.
They are 25th in the league phase of the Champions League, having lost once and drawn twice in their opening three matches.