The Old Lady have named previous Italian national team manager the veteran manager to take the helm for the remainder of the campaign.
Spalletti takes over from Igor Tudor, who was let go post the Lazio setback last weekend.
The former boss came on board in March as Thiago Motta's replacement but exited following a seven-month stint after an eight-game winless streak.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, after the team's failure to reach the 2022 World Cup under former boss Roberto Mancini.
He helped them qualify for Euro 2024 where they were knocked out in the last 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June after a World Cup qualifying defeat by Norway, as Italy faced the possibility of not making a third World Cup in a row.
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 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.
They are 25th in the league phase of the Champions League, with one loss and two draws in their first three games.
