The Old Lady have chosen ex- Azzurri boss the veteran manager as their manager until the end of the season.
Spalletti replaces Igor Tudor, who was sacked after the Serie A side's defeat by Lazio last weekend.
The former boss came on board in March as Thiago Motta's replacement 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, after the team's failure to reach 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.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, with the Azzurri at risk of missing out on a third consecutive World Cup.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and won the Russian Premier League twice with Zenit St Petersburg.
Massimo Brambilla took interim charge of 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, after recording one defeat and two ties in the initial three fixtures.
