Vicario, 26, has signed a contract lasting five years and will wear the number 13 shirt for Spurs.
The Italy international impressed for Empoli during a two-year spell, which earned him a first international call-up last September.
Vicario started his career at Udinese and had spells at Cagliari, Perugia and Venezia before joining Empoli in July 2021.
He made 31 appearances last season keeping seven clean sheets as Empoli finished in 14th place in Serie A.
Vicario is likely to serve as a replacement for Spurs captain Hugo Lloris, whose 11-year spell at the club could come to an end this summer.
The Frenchman has one year remaining on his contract and signalled his intent to embark on a fresh challenge.