The Old Lady have named ex- Italy head coach the veteran manager to take the helm for the remainder of the campaign.
Spalletti replaces 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 exited following a seven-month stint following a string of eight matches without a victory.
Spalletti guided Napoli to the Serie A crown in 2022-23 before taking charge of Italy, which missed out on the 2022 World Cup during Roberto Mancini's tenure.
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.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and secured two Russian Premier League titles with Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus during the 3-1 victory over Udinese on Wednesday placing them seventh in the Serie A standings - six points adrift of Napoli at the top after nine rounds.
Their Champions League campaign sees them in 25th place in the group stage, with one loss and two draws in their first three games.
