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Italy international Tonali joined Newcastle from AC Milan for £55m in July 2023.
He was banned for 10 months by the Italian Football Federation (FIGC) for breaching betting rules shortly after his arrival.
But he became a key player on his return and helped Newcastle win the Carabao Cup in 2025 - their first trophy in 70 years.
In a social media post,, external Tonali said it was "time to say goodbye" to the Magpies and manager Eddie Howe, although "it's hard to find the right words" as he also thanked the club's fans for their support.
"Thank you to the staff and my team-mates for believing in me and helping me grow," he wrote.
"A special mention to the gaffer, Eddie, who's been a real guiding figure and who always had my back throughout this journey.
"This city gave me more than football. It gave me a home, moments I'll hold onto forever, and people I will always be grateful for. Thank you for everything."
Spurs boss De Zerbi, who took over at Tottenham at the end of March and narrowly saved the club from Premier League relegation, described Tonali as a "special player".
He added: "I have followed him for a long time, as he came through the youth system at my hometown club, Brescia, and I'm so happy to be working with him now.
"Given his qualities, there was a lot of interest in Sandro this summer. However, he was very clear in his desire to join Tottenham, and I know our fans will love what he brings to the team."
It has been a busy summer for Tottenham after they finished 17th - and two points above the relegation zone - in the Premier League last season.
Defenders Andy Robertson and Marcos Senesi have arrived on free transfers and the club could end up spending a combined £237m on centre-back Jan Paul van Hecke and midfielders Fernandes and Tonali.
"He [Tonali] has outstanding technical quality to go with real football intelligence, and has the character to thrive in a demanding, high-pressure environment," said Spurs sporting director Johan Lange.
