The Old Lady have appointed previous Azzurri manager Spalletti to lead the team until the end of the season.
The 66-year-old takes over from Igor Tudor, who was dismissed post the Lazio setback last weekend.
Tudor had joined the club in March as Thiago Motta's replacement but departed after seven months following a string of eight matches without a victory.
Spalletti led Napoli to the Serie A title in 2022-23 before taking charge of Italy, who had failed to qualify for the 2022 World Cup during Roberto Mancini's tenure.
Under his guidance, they made it to Euro 2024 where they were knocked out in the last 16 by Switzerland.
However, Spalletti was sacked by Italy in June post a qualifying defeat against 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 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, with one loss and two draws in their first three games.