Juventus have chosen previous Azzurri head coach the veteran manager to take the helm until the end of the season.
Spalletti steps in for Igor Tudor, who was dismissed post the Lazio setback on Sunday.
Tudor arrived at the club in March filling the shoes of Thiago Motta but left after seven months after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, which missed out on the 2022 World Cup during Roberto Mancini's tenure.
Under his guidance, they made it to Euro 2024 but were eliminated in the round of 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June following a loss to Norway in World Cup qualifying, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla served as interim manager for 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.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.