The match at the Tottenham Hotspur stadium was put in doubt on Tuesday after Fulham returned a number of positive COVID-19 tests earlier this week. The match was scheduled to kick off at 6 p.m. (1 p.m. ET).
A Premier League statement read: "The match between Tottenham Hotspur and Fulham, due to be played at 18:00 GMT this evening, has been postponed following a Premier League Board meeting this afternoon.
"Fulham lodged a request with the Premier League Board to rearrange the fixture following a significant rise in positive COVID-19 cases, as well as a number of players showing symptoms today.
"The Premier League Board has consulted its medical advisors and the decision to postpone the game has been taken as a precaution and with the health of players and staff as the priority. The group will now be retested immediately.
"With low numbers of positive tests across the overwhelming majority of clubs, the Premier League continues to have full confidence in its COVID-19 protocols and being able to continue to play our fixtures as scheduled.
"The League wishes those with COVID-19 a safe and speedy recovery and will rearrange the postponed fixture between Tottenham Hotspur and Fulham in due course."
Four hours before the game was scheduled to kick off, Spurs boss Jose Mourinho said he was still in the dark regarding the status of the match.
He wrote on Instagram: "Match at 6 pm... We still don't know if we play. Best league in the world."
It comes after the Premier League received a total of 18 positive COVID-19 tests on Tuesday -- the highest recorded in the testing programme.
A Tottenham statement read: "The Premier League informed us of the decision this afternoon, with Fulham having requested the postponement on the grounds of the number of COVID-19 positive cases among their players and staff.
"Everyone at Tottenham Hotspur sends their best wishes to Fulham for a safe and speedy recovery to all those who are affected."
Fulham also released a statement: "This decision follows discussions with the Premier League and advice from Public Health England.
"Those players and staff who tested positive have been self-isolating in line with UK Government and Premier League guidance. We wish the players and staff who tested positive a safe and speedy recovery."
This becomes the third Premier League match to be postponed this season after Manchester City's clash at Everton was called off on Monday. Newcastle United's clash against Aston Villa was postponed earlier this month.
Mourinho's Spurs side had the opportunity to climb into third place but will remain in sixth position while Fulham stay in the relegation zone.
However, he was set to return to the dugout on Wednesday after a negative test at the weekend.
Information from Reuters was included in this report.