Juventus have appointed previous Italy boss the veteran manager to lead the team for the remainder of the campaign.
The experienced coach takes over from the Croatian manager, who was let go post the Lazio setback last weekend.
The former boss came on board in March to replace Thiago Motta but left after seven months 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, which missed out on the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 where they were knocked out in the last 16 by Switzerland.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla 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.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.