The Old Lady have appointed previous Azzurri head coach the veteran manager as their manager for the remainder of the campaign.
The 66-year-old takes over from Igor Tudor, who was sacked post the Lazio setback on Sunday.
Tudor had joined the club in March filling the shoes of Thiago Motta but departed after seven months at the end of an eight-match winless run.
Spalletti led Napoli to the Serie A title in 2022-23 then moving on to lead the Italian national team, 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 post a qualifying defeat against 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 - trailing leaders Napoli by six points after nine matches.
Their Champions League campaign sees them in 25th place in the group stage, having lost once and drawn twice in their opening three matches.
