The Old Lady have named former Italian national team head coach Spalletti as their manager until the end of the season.
The 66-year-old steps in for Igor Tudor, who was let go after the Serie A side's defeat by Lazio recently.
Tudor had joined the club in March to replace Thiago Motta but left 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, after the team's failure to reach 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.
Yet, the Italian FA let Spalletti go in June after a World Cup qualifying defeat by Norway, as Italy faced the possibility of not making a third World Cup in a row.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla in the midweek 3-1 triumph over Udinese placing them seventh in the Serie A standings - 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.