The Old Lady have chosen former Italy manager the veteran manager as their manager for the rest of the term.
The experienced coach takes over from Igor Tudor, who was dismissed following the loss to Lazio last weekend.
Tudor arrived at the club in March as Thiago Motta's replacement but left after seven months after an eight-game winless streak.
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.
He helped them qualify for Euro 2024 but were eliminated in the round of 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.
Spalletti's managerial career includes Inter Milan, Roma, and Udinese in Serie A and secured two Russian Premier League titles 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 - six points behind leaders Napoli after nine games.
They are 25th in the league phase of the Champions League, having lost once and drawn twice in their opening three matches.