The Italian, who rejoined the club in October in a formal capacity, will leave at the end of the winter transfer window to take up a role at Serie A side Fiorentina.
Paratici said: "I want to thank (chief executive) Vinai (Venkatesham) and the board of Tottenham for accommodating my desire to return to Italy and join Fiorentina.
"I have loved my time at the club, however this opportunity, together with the need to be based in my homeland, has led me to this decision.
"Spurs is a club that is very close to my heart.
"It has great people working for it, who are as passionate about the project as I am and want to bring sustained success.
"I have no doubt that they will achieve that and I will be watching closely from Italy."
Paratici left in 2023 due to allegations of false accounting at former club Juventus.
The Italian subsequently received a 30-month ban imposed by FIFA.
Despite the ban, Paratici continued working with Spurs as a consultant before officially returning to his role earlier this season.
However, speculation over a return to Italy had been mounting since late December, with reports linking him to Fiorentina.
The London club recently recalled Manor Solomon from a loan spell at Villarreal and sent him to Fiorentina, a move that raised eyebrows amid the ongoing speculation around Paratici’s future.
Tottenham’s chief executive Vinai Venkatesham said: "We have agreed that Fabio will return to Italy following the conclusion of the January transfer window, in line with his wish to move back home.
"We thank Fabio for his contribution to the club and wish him well for the future."
Spurs head coach Thomas Frank addressed the ongoing rumours last week.
He said: "We’re paying his wage, he’s working very hard."
The January transfer window, which closes on February 2, will now mark the end of his time in north London.