The Old Lady have appointed previous Azzurri manager the veteran manager as their manager for the rest of the term.
The 66-year-old replaces the Croatian manager, who was sacked post the Lazio setback on Sunday.
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 led Napoli to the Serie A title in 2022-23 then moving on to lead the Italian national team, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
Under his guidance, they made it to Euro 2024 where they were knocked out in the last 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June after a World Cup qualifying defeat by 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 lifted the Russian league trophy twice while at Zenit St Petersburg.
Massimo Brambilla took interim charge of Juventus during the 3-1 victory over Udinese on Wednesday which left them seventh in Serie A - 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.
