The Serie A powerhouse have appointed ex- Italy boss the veteran manager as their manager until the end of the season.
Spalletti replaces Igor Tudor, who was dismissed post the Lazio setback on Sunday.
Tudor arrived at the club in March filling the shoes of Thiago Motta but exited following a seven-month stint after an eight-game winless streak.
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 helped them qualify for Euro 2024 but were eliminated in the round of 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June post a qualifying defeat against Norway, as Italy faced the possibility of not making a third World Cup in a row.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla served as interim manager for Juventus for their 3-1 win against Udinese on Wednesday moving them to seventh position in the league - trailing leaders Napoli by six points after nine matches.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.
