Juventus have chosen previous Italian national team manager the veteran manager to take the helm for the rest of the term.
The experienced coach takes over from Igor Tudor, who was let go post the Lazio setback last weekend.
Tudor arrived at the club in March as Thiago Motta's replacement 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 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
He helped them qualify for Euro 2024 exiting in the last 16 stage against Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, putting Italy in danger of missing a third straight World Cup.
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.
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 - 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.