The Serie A powerhouse have chosen ex- Italian national team head coach Spalletti to take the helm for the remainder of the campaign.
The experienced coach steps in for Igor Tudor, who was let go post the Lazio setback last weekend.
The former boss came on board in March filling the shoes of Thiago Motta but departed after seven months following a string of eight matches without a victory.
Spalletti led Napoli to the Serie A title in 2022-23 prior to assuming the Italy role, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to 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.
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 took interim charge of Juventus in the midweek 3-1 triumph over Udinese moving them to seventh position in the league - six points behind leaders Napoli after nine games.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.