The Serie A powerhouse have named former Italian national team head coach the veteran manager to take the helm until the end of the season.
The 66-year-old replaces Igor Tudor, who was sacked post the Lazio setback recently.
Tudor arrived at the club in March filling the shoes of 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 before taking charge of Italy, who had failed to qualify for the 2022 World Cup under former boss Roberto Mancini.
Under his guidance, they made it to Euro 2024 exiting in the last 16 stage against Switzerland.
However, Spalletti was sacked by Italy in June after a World Cup qualifying defeat by Norway, putting Italy in danger of missing a third straight World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight 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 which left them seventh in Serie A - six points behind leaders Napoli after nine games.
In the Champions League, they sit 25th in the league phase, having lost once and drawn twice in their opening three matches.
