The Serie A powerhouse have appointed ex- Azzurri manager Spalletti to take the helm until the end of the season.
The 66-year-old steps in for his predecessor, 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 at the end of an eight-match winless run.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
He helped them qualify for Euro 2024 where they were knocked out in the last 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June following a loss to Norway in World Cup qualifying, putting Italy in danger of missing a third straight World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against Udinese on Wednesday which left them seventh in Serie A - six points behind leaders Napoli after nine games.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.
