Juventus have chosen ex- Azzurri boss the veteran manager to take the helm for the remainder of the campaign.
The 66-year-old replaces the Croatian manager, who was sacked post the Lazio setback last weekend.
The former boss came on board in March as Thiago Motta's replacement but exited following a seven-month stint following a string of eight matches without a victory.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 but were eliminated in the round of 16 by Switzerland.
However, Spalletti was sacked by Italy in June following a loss to Norway in World Cup qualifying, as Italy faced the possibility of not making a third World Cup in a row.
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 - trailing leaders Napoli by six points after nine matches.
Their Champions League campaign sees them in 25th place in the group stage, after recording one defeat and two ties in the initial three fixtures.
