Juventus have appointed ex- Italy boss the veteran manager to take the helm for the rest of the term.
The 66-year-old steps in for Igor Tudor, who was dismissed following the loss to Lazio recently.
Tudor had joined the club in March filling the shoes of Thiago Motta but exited following a seven-month stint after an eight-game winless streak.
Spalletti led Napoli to the Serie A title in 2022-23 prior to assuming the Italy role, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 but were eliminated in the round of 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June post a qualifying defeat against Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti has also managed Inter Milan, Roma and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus in the midweek 3-1 triumph over Udinese placing them seventh in the Serie A standings - 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.