Juventus have named previous Italian national team manager the veteran manager to take the helm for the remainder of the campaign.
The 66-year-old steps in for Igor Tudor, who was dismissed post the Lazio setback recently.
Tudor had joined the club in March filling the shoes of Thiago Motta but left after seven months after an eight-game winless streak.
Spalletti led Napoli to the Serie A title in 2022-23 then moving on to lead the Italian national team, after the team's failure to reach the 2022 World Cup during Roberto Mancini's tenure.
He helped them qualify for Euro 2024 exiting in the last 16 stage against Switzerland.
Yet, the Italian FA let Spalletti go in June after a World Cup qualifying defeat by Norway, putting Italy in danger of missing a third straight World Cup.
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 served as interim manager for Juventus in the midweek 3-1 triumph over Udinese moving them to seventh position in the league - six points adrift of Napoli at the top after nine rounds.
Their Champions League campaign sees them in 25th place in the group stage, with one loss and two draws in their first three games.