The Old Lady have named previous Italian national team manager the veteran manager as their manager until the end of the season.
The 66-year-old replaces the Croatian manager, who was let go after the Serie A side's defeat by Lazio recently.
The former boss came on board in March to replace 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.
Nonetheless, Italy dismissed Spalletti in June post a qualifying defeat against Norway, with the Azzurri at risk of missing out on a third consecutive 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 during the 3-1 victory over Udinese on Wednesday moving them to seventh position in the league - trailing leaders Napoli by six points after nine matches.
In the Champions League, they sit 25th in the league phase, with one loss and two draws in their first three games.