The Argentinian had spent five-and-a-half years in North London and helped take Spurs to the Champions League final last season where they lost to Liverpool.
However, a poor start to this campaign has seen the team tipped as title contenders sit 14th in the Premier League.
Pochettino’s last game in charge before the international break was a home draw with Sheffield United – a match in which the visitors deserved to take all three points.
Chairman Daniel Levy, who appointed Pochettino in June 2014, said: "We were extremely reluctant to make this change and it is not a decision the board have taken lightly, nor in haste.
Sheffield Wednesday boss and chairman unhappy after attackers leave for Premier League
Darren Moore dismisses Barry Bannan over-reliance notion after surprise Sheffield Wednesday sub call
Why Sheffield Wednesday left Dennis Adeniran out completely against Charlton Athletic
Chris Wilder says Sheffield United "ready to rock and roll" after Middlesbrough draw
Sheffield Wednesday mull over loan offers - confirm that one has been rejected
"Regrettably domestic results at the end of last season and the beginning of this season have been extremely disappointing.
"It falls on the board to make the difficult decisions - this one made more so given the many memorable moments we have had with Mauricio and his coaching staff - but we do so in the club's best interests."
Tottenham take on West Ham this weekend.