The Serie A powerhouse have named former Italy manager Spalletti to lead the team until the end of the season.
The experienced coach replaces the Croatian manager, who was dismissed post the Lazio setback last weekend.
The former boss came on board in March to replace Thiago Motta but exited following a seven-month stint after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown in 2022-23 then moving on to lead the Italian national team, 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 post a qualifying defeat against Norway, as Italy faced the possibility of not making a third World Cup in a row.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus for their 3-1 win against Udinese on Wednesday moving them to seventh position in the league - 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.