Ange Postecoglou's side have parted with £17.2m for the Italian's services.
Vicario is set to take over as Tottenham's number one goalkeeper next season, with Hugo Lloris expected to move on this summer after eleven years at the club.
Vicario spent two seasons with Empoli in the Italian Serie A, making 71 appearances in total and helping them preserve their top flight status with consecutive 14th place finishes.
The 26-year-old is Tottenham's second summer signing following the permanent acquisition of Dejan Kulusevski on a permanent deal from Juventus.
Vicario is yet to make his senior debut for the Italian national team but has been named as part of recent squads by Roberto Mancini.
A statement from Tottenham Hotspurs read: "We are delighted to announce the signing of Guglielmo Vicario from Empoli, subject to international clearance and a work permit.
"The Italy international has signed a contract with the Club that will run until 2028 and will wear the number 13 shirt.
Tottenham will not play European football next season after finishing eight in the Premier League.
