Juventus have chosen previous Azzurri manager the veteran manager as their manager until the end of the season.
The experienced coach steps in for his predecessor, who was sacked post the Lazio setback recently.
The former boss came on board in March as Thiago Motta's replacement but exited following a seven-month stint at the end of an eight-match winless run.
Spalletti guided Napoli to the Serie A crown in 2022-23 then moving on to lead the Italian national team, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 exiting in the last 16 stage against Switzerland.
Yet, the Italian FA let Spalletti go in June following a loss to Norway in World Cup qualifying, 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 won the Russian Premier League twice with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla for their 3-1 win against Udinese on Wednesday which left them seventh in Serie A - trailing leaders Napoli by six points after nine matches.
In the Champions League, they sit 25th in the league phase, after recording one defeat and two ties in the initial three fixtures.
