The NFL has cancelled the four games scheduled to take place in London later this year.
Two fixtures involving the Jacksonville Jaguars were scheduled for Wembley, with two more matches due to be played at the Tottenham Hotspur Stadium.
They will now be held in the US after organisers decided it was impossible to arrange games in a different continent because of the coronavirus pandemic.
The London games were set for autumn 2020, but no firm dates had been set.
It will be the first time an NFL regular season game has not been played in London since 2006.
NFL commissioner Roger Goodell made the decision after consultation with a number of stakeholders including clubs, local governments and medical authorities.
The Mayor of London Sadiq Khan said it was “absolutely the right decision to ensure the safety of everyone involved in the sport”, while Tottenham chairman Daniel Levy said they “fully appreciate the difficult decision that the NFL has had to make”.
The NFL had also been planning to play one game at the Azteca Stadium in Mexico, but that too will now take place in the USA.
NFL UK managing director Alistair Kirkwood added: “The NFL’s London Games have become a major part of the NFL season and the UK sports calendar.
“But the uncertainty in the current sporting landscape and the tremendous amount of long-term travel and planning required to stage successful London games mean this is the sensible decision to make.”
BBC Sport’s Simon Stone:
This news is hardly unexpected given no-one knows when top-level sport will be played in the United Kingdom – and when it is, it will almost certainly be behind closed doors for the remainder of 2020 at least.
However, it is another financial blow to both Tottenham and the Football Association, given the games have proved themselves to be useful money-spinners over the years.
The company responsible for the technology that allows beer to be filled from the bottom of the glass upwards at the Tottenham Hotspur Stadium posted on social media that they had taken £1m for the first of the two games last year – and with the club netting most of the profits from merchandise sales as well, it is fair to assume they have missed out on about £4m in income.
It is yet another example of the financial pain Covid-19 is causing sport and underlines why Tottenham chairman Daniel Levy said in March he was facing the biggest problems he has encountered in 20 years at the club.