The Old Lady have chosen ex- Italy head coach Spalletti to lead the team for the rest of the term.
Spalletti replaces Igor Tudor, who was sacked following the loss to Lazio last weekend.
Tudor arrived at the club in March to replace Thiago Motta but left after seven months following a string of eight matches without a victory.
Spalletti guided Napoli to the Serie A crown in 2022-23 prior to assuming the Italy role, which missed out on the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 where they were knocked out in the last 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June after a World Cup qualifying defeat by Norway, putting Italy in danger of missing a third straight World Cup.
Spalletti has also managed 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 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.
Their Champions League campaign sees them in 25th place in the group stage, after recording one defeat and two ties in the initial three fixtures.