The Portuguese replaced Mauricio Pochettino as Spurs manager in November 2019 and guided the club to sixth in the Premier League last season.
They are currently seventh, having picked up two points from their past three league games, and were knocked out of the Europa League in March.
Spurs face Manchester City in the Carabao Cup final on 25 April.
On Sunday, Tottenham were one of six Premier League clubs to announce they were joining a new European Super League.
Mourinho’s coaching staff of Joao Sacramento, Nuno Santos, Carlos Lalin and Giovanni Cerra have also been sacked.
“Jose and his coaching staff have been with us through some of our most challenging times as a club,” said Tottenham chairman Daniel Levy. “Jose is a true professional who showed enormous resilience during the pandemic.
“On a personal level I have enjoyed working with him and regret that things have not worked out as we both had envisaged.
“He will always be welcome here and we should like to thank him and his coaching staff for their contribution.”
This season, Mourinho suffered 10 league defeats in a single campaign for the first time in his managerial career.
No Premier League side has lost more points from winning positions this season than Spurs, who have dropped 20.
Mourinho’s last game in charge was a 2-2 league draw at Everton on Friday.
Former Spurs midfielder Ryan Mason, who has been working with the club’s academy, will take first-team training on Monday.