The Serie A powerhouse have named former Azzurri head coach the veteran manager to take the helm for the rest of the term.
The experienced coach takes over from Igor Tudor, who was let go post the Lazio setback on Sunday.
Tudor had joined the club in March filling the shoes of Thiago Motta but left after seven months after an eight-game winless streak.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 then moving on to lead the Italian national team, after the team's failure to reach the 2022 World Cup during Roberto Mancini's tenure.
He secured their spot in Euro 2024 where they were knocked out in the last 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June following a loss to Norway in World Cup qualifying, with the Azzurri at risk of missing out on a third consecutive World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus for their 3-1 win against 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.
