Conte has been signed to an initial 18-month contract and gets reunited with the club's football director, Fabio Paratici, whom he worked with at Juventus.
Tottenham sacked Esperito Santo after just four months in charge on Monday after an indifferent start to the season.
The North London club are eighth on the Premier League table, having won five and lost five of their ten games.
Conte's appointment marks a return to England where he won the Premier League and FA Cup in a two-year stint at Chelsea.
He also has four Serie A titles to his name as a manager; three with Juventus and one with Inter Milan last season.
“I am extremely happy to return to coaching, and to do so at a Premier League club that has the ambition to be a protagonist again", Conte said after his appointment was confirmed.
“Tottenham Hotspur has state-of-the-art facilities and one of the best stadiums in the world. I can't wait to start working to convey to the team and the fans the passion, mentality and determination that have always distinguished me, as a player and as a coach.
“Last summer our union did not happen because the end of my relationship with Inter was still too recent and emotionally too involved with the end of the season, so I felt that it wasn’t yet the right time to return to coaching.
“But the contagious enthusiasm and determination of Daniel Levy in wanting to entrust me with this task had already hit the mark. Now that the opportunity has returned, I have chosen to take it with great conviction.”
Paratici added: “We are delighted to welcome Antonio to the Club. His track record speaks for itself, with vast experience and trophies in both Italy and England.
“I know first-hand the qualities Antonio can bring to us, having worked with him at Juventus, and look forward to seeing his work with our talented group of players.”