The Old Lady have named ex- Italy manager the veteran manager to lead the team for the remainder of the campaign.
The 66-year-old takes over from Igor Tudor, who was let go post the Lazio setback recently.
Tudor had joined the club in March to replace Thiago Motta but exited following a seven-month stint at the end of an eight-match winless run.
Spalletti guided Napoli to the Serie A crown 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 helped them qualify for 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, 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 secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla served as interim manager for 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.
In the Champions League, they sit 25th in the league phase, after recording one defeat and two ties in the initial three fixtures.
