The Old Lady have chosen previous Italy head coach the veteran manager to take the helm for the remainder of the campaign.
The experienced coach steps in for the Croatian manager, who was dismissed after the Serie A side's defeat by Lazio recently.
The former boss came on board in March as Thiago Motta's replacement but departed after seven months after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown 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 helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June after a World Cup qualifying defeat by Norway, putting Italy in danger of missing a third straight World Cup.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla 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.
Their Champions League campaign sees them in 25th place in the group stage, after recording one defeat and two ties in the initial three fixtures.