The Old Lady have named previous Italian national team manager Spalletti as their manager for the remainder of the campaign.
The 66-year-old steps in for Igor Tudor, who was sacked post the Lazio setback recently.
The former boss came on board in March to replace Thiago Motta but exited following a seven-month stint following a string of eight matches without a victory.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, after the team's failure to reach 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.
Nonetheless, Italy dismissed Spalletti 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 has also managed Inter Milan, Roma and Udinese in Serie A and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against 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, with one loss and two draws in their first three games.
