British media reported that Italian champions Inter paid around £30 million ($40.59 million) for the 26-year-old.
"The English wing-back, born in 2000, joins the Nerazzurri from Tottenham Hotspur on a permanent transfer; Spence has signed a contract with the Club until 30 June 2031," the club said in a statement.
Spence departs from North London after four years, where he made 85 appearances and won the Europa League. Limited first-team opportunities saw him spend time on loan at Stade Rennais, Leeds United and Genoa before eventually establishing himself at Spurs.
The England international was also part of Thomas Tuchel's squad at the 2026 World Cup, making eight appearances, including in England's victory in the third-place play-off.
At Inter, Spence will link up with defender John Stones, who joined the Italian club on a two-year contract after leaving Manchester City.
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