Southampton announced Tuesday afternoon that the Argentine had left the Saints, with Spurs releasing official confirmation shortly afterward.
Pochettino has signed a five-year deal with Spurs. He replaces Tim Sherwood, who was sacked at the end of last season having only taken over from Andre Villas-Boas in December.
Pochettino, who will bring several members of his coaching staff with him to White Hart Lane, said: "This is a Club with tremendous history and prestige, and I am honored to have been given this opportunity to be its Head Coach.
"There is an abundance of top-class talent at the club, and I am looking forward to starting work with the squad.
"Tottenham Hotspur has a huge following across the world and I have great admiration for the passion the fans show for this team. We are determined to give the supporters the kind of attacking football and success that we are all looking to achieve."
The Club is delighted to announce the appointment of Mauricio Pochettino as our new Head Coach on a five-year contract.— Tottenham Hotspur (@SpursOfficial) May 27, 2014
Chairman Daniel Levy added: "In Mauricio I believe we have a head coach who, with his high energy, attacking football, will embrace the style of play we associate with our club. He has a proven ability to develop each player as an individual, whilst building great team spirit and a winning mentality.
"We have a talented squad that Mauricio is excited to be coaching next season."
Jesus Perez will join as assistant Head Coach, Miguel D'Agostino has been named first team coach and Toni Jimenez will work as goalkeeper coach.