The news comes after Villa were forced to field a team consisting of U23 and U18 players against Liverpool in the FA Cup, following a coronavirus outbreak hitting the first-team set-up at Bodymoor Heath.
Villa's training ground was closed on Thursday, when it emerged that 14 members of first-team players and staff had returned positive tests.
Rules in regards to the Premier League differ to the FA Cup, and previous games affected by outbreaks involving other sides were postponed and rearranged - that is now the case with Villa for the clash with Spurs.
Fulham, who themselves suffered an outbreak earlier this season, will now take on Tottenham at short notice in place of Villa - after the previous fixture between the sides was postponed.
The Cottagers' game with Chelsea has been pushed back to allow for more time between the fixtures.
Meanwhile, Villa's Premier League clash with Everton is now due to take place on Sunday at midday, having previously been due to go ahead on Saturday.
The Premier League confirmed the decision, after Villa requested for the fixture to be rearranged.
"Aston Villa's match against Tottenham Hotspur, due to be played at Villa Park on Wednesday 13 January, has been rescheduled following a decision by the Premier League Board." The statement read.
"Following Aston Villa's request to rearrange the fixture, and due to the number of players and staff who have either tested positive for COVID-19 or have been placed in isolation by the club, the Premier League had no other option than to reschedule the match.
"With the health of players and staff the priority, the League continues to work with Aston Villa on measures to ensure their League season resumes safely and at the earliest opportunity.
"The Premier League wishes those with COVID-19 a full and swift recovery and will rearrange Aston Villa's match against Spurs as soon as possible."
Villa published a similar statement, adding their thanks to the Premier League, Public Health England and Spurs for their understanding of the ongoing situation at the club.
"The club has been in dialogue with the Premier League and Public Health England since the training ground was closed last Thursday following a significant Covid-19 outbreak among first team players and staff." the club said.
"The club would like to thank the Premier League, Public Health England and Tottenham Hotspur for their understanding of our unprecedented and unique situation."