The Old Lady have chosen ex- Italian national team manager Spalletti to take the helm for the remainder of the campaign.
Spalletti replaces Igor Tudor, who was sacked following the loss to Lazio last weekend.
Tudor had joined the club in March to replace Thiago Motta but left 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, which missed out on 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.
Nonetheless, Italy dismissed Spalletti 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 won the Russian Premier League twice 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.