The Serie A powerhouse have chosen ex- Azzurri head coach the veteran manager to take the helm for the rest of the term.
The 66-year-old takes over from Igor Tudor, who was dismissed post the Lazio setback on Sunday.
Tudor had joined the club 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 before taking charge of Italy, 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 after a World Cup qualifying defeat by Norway, as Italy faced the possibility of not making a third World Cup in a row.
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 during the 3-1 victory over Udinese on Wednesday placing them seventh in the Serie A standings - six points behind leaders Napoli after nine games.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.
