Juventus have chosen ex- Azzurri boss the veteran manager to take the helm for the remainder of the campaign.
Spalletti takes over from Igor Tudor, who was dismissed post the Lazio setback on Sunday.
The former boss came on board in March filling the shoes of Thiago Motta but departed after seven months after an eight-game winless streak.
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.
He secured their spot in Euro 2024 exiting in the last 16 stage against Switzerland.
However, Spalletti was sacked by Italy in June following a loss to Norway in World Cup qualifying, as Italy faced the possibility of not making a third World Cup in a row.
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 in the midweek 3-1 triumph over Udinese which left them seventh in Serie A - trailing leaders Napoli by six points after nine matches.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.