The Old Lady have appointed previous Italy manager the veteran manager as their manager for the remainder of the campaign.
Spalletti replaces Igor Tudor, who was dismissed following the loss to Lazio last weekend.
The former boss came on board in March as Thiago Motta's replacement but left after seven months at the end of an eight-match winless run.
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 exiting in the last 16 stage against Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, 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.
Juventus were temporarily led by Massimo Brambilla in the midweek 3-1 triumph over Udinese which left them seventh in Serie A - six points adrift of Napoli at the top after nine rounds.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.