The Serie A powerhouse have appointed ex- Azzurri head coach Spalletti to lead the team until the end of the season.
The experienced coach replaces Igor Tudor, who was let go post the Lazio setback last weekend.
Tudor had joined the club in March as Thiago Motta's replacement but exited following a seven-month stint following a string of eight matches without a victory.
Under Spalletti, Napoli clinched the Serie A championship in 2022-23 prior to assuming the Italy role, who had failed to qualify for the 2022 World Cup during Roberto Mancini's tenure.
Under his guidance, they made it to Euro 2024 but were eliminated in the round of 16 by Switzerland.
Nonetheless, Italy dismissed Spalletti in June post a qualifying defeat against Norway, 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 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 which left them seventh in Serie A - six points adrift of Napoli at the top after nine rounds.
They are 25th in the league phase of the Champions League, after recording one defeat and two ties in the initial three fixtures.