Juventus have named previous Italian national team head coach the veteran manager to take the helm for the remainder of the campaign.
Spalletti takes over from Igor Tudor, who was dismissed post the Lazio setback on Sunday.
The former boss came on board in March to replace Thiago Motta but departed after seven months following a string of eight matches without a victory.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, which missed out on 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.
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.
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.
Juventus were temporarily led by Massimo Brambilla in the midweek 3-1 triumph over Udinese placing them seventh in the Serie A standings - trailing leaders Napoli by six points after nine matches.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.
