Juventus have named former Azzurri manager the veteran manager to lead the team for the rest of the term.
Spalletti steps in for Igor Tudor, who was sacked following the loss to Lazio recently.
Tudor had joined the club in March to replace Thiago Motta 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 then moving on to lead the Italian national team, which missed out on 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.
Yet, the Italian FA let Spalletti go 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 won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus during the 3-1 victory over Udinese on Wednesday 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, after recording one defeat and two ties in the initial three fixtures.
