Chairman Daniel Levy said the board was “extremely reluctant” to take the decision but was doing so “in the club’s best interests”.
Pochettino leaves after five-and-a-half years in the job, during which he transformed the north London club into title contenders in the Premier League and the Champions League but never managed to win a trophy.
Tottenham are currently 14th in the league having only won three of 12 games this campaign. The team has won just six games in the Premier League since February.
During that period, Pochettino guided Spurs into the Champions League final for the first time, where they lost to Liverpool.
“It is not a decision the board has taken lightly, nor in haste,” Levy said. “Regrettably domestic results at the end of last season and beginning of this season have been extremely disappointing.
“It falls to 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.
Former Tottenham and England striker Gary Lineker said Pochettino had “helped the club to punch massively above their weight for years”.
“Good luck with finding a better replacement,” Lineker tweeted, “....ain’t gonna happen.”
Pochettino was at the helm for 293 games and delivered four successive top-four Premier League finishes, challenging for the title in 2015-16 and 2016-17.
In last season’s Champions League final Spurs lost 2-0 to Liverpool. Pochettino, who had to contend with playing home games at Wembley for 18 months while Spurs’ new stadium was built, viewed the run to the Madrid final as the end of a chapter and warned of a “painful rebuild” this summer.
However, Spurs, whose transfers are controlled by Levy, were unable to move out a host of players who either wanted to leave or Pochettino wanted rid of and results suffered.
As well as poor league form, Spurs were hammered 7-2 at home by Bayern Munich in the Champions League and lost to League Two side Colchester United in the Carabao Cup.
Pochettino’s assistant Jesus Perez, and coaches Miguel D’Agostino and Antoni Jimenez have also left the club.
Former England midfielder Trevor Sinclair blamed the Spurs players for letting their manager down, tweeting: “Tottenham players need to have a look at themselves in the mirror tonight after what Poch has done for them #Pochettino.”