The Old Lady have appointed ex- Azzurri boss Spalletti to take the helm for the remainder of the campaign.
Spalletti replaces the Croatian manager, who was let go after the Serie A side's defeat by Lazio on Sunday.
The former boss came on board in March filling the shoes of Thiago Motta but left after seven months 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, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 exiting in the last 16 stage against Switzerland.
Nonetheless, Italy dismissed Spalletti 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 took interim charge of Juventus in the midweek 3-1 triumph over Udinese which left them seventh in Serie A - six points behind leaders Napoli after nine games.
Their Champions League campaign sees them in 25th place in the group stage, with one loss and two draws in their first three games.