The 42-year-old Argentine has agreed a five-year contract with Spurs after seeing his resignation accepted at Southampton.
Pochettino, who replaces Tim Sherwood at White Hart Lane, leaves the Saints following a 14-month spell in charge.
He guided Southampton to an eighth-place finish in the Premier League table last season - his first full campaign as manager of the team.
"This is a club with tremendous history and prestige and I am honoured to have been given this opportunity to be its head coach," he told Tottenham's official website.
"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."