The Old Lady have appointed ex- Italian national team manager Spalletti as their manager until the end of the season.
Spalletti takes over from Igor Tudor, who was let go 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 at the end of an eight-match winless run.
Under Spalletti, Napoli clinched the Serie A championship 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 but were eliminated in the round of 16 by Switzerland.
However, Spalletti was sacked by Italy 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.
Massimo Brambilla took interim charge of 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.