The 26-year-old joins the London club after three seasons with the Magpies.
Spurs had a bid of around £80m rejected by Newcastle, but reached agreement on a deal where they are expected to pay an initial £92.5m plus a further £7.5m in add-ons.
Tonali joins fellow big-money signing Mateus Fernandes, who moved from West Ham to Spurs for a fee of £85m.
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.
Spurs boss Roberto de Zerbi identified his countryman as a target during his time in charge of Sassuolo several years ago when Tonali was playing in Serie A.
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.
