Juventus have named former Azzurri boss the veteran manager to take the helm until the end of the season.
The experienced coach 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 left 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, which missed out on the 2022 World Cup under former boss Roberto Mancini.
Under his guidance, they made it to Euro 2024 where they were knocked out in the last 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus in the midweek 3-1 triumph over Udinese which left them seventh in Serie A - trailing leaders Napoli by six points after nine matches.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.