Wembley Stadium is to host two NFL games in 2013 in a deal that is set to boost London's economy by £22 million, London Mayor Boris Johnson said on Wednesday.
The Minnesota Vikings will play six-time Super Bowl champions the Pittsburgh Steelers on September 29 next year.
The NFL had already confirmed that Jacksonville Jaguars and San Francisco 49ers will play on October 27, 2013.
Johnson hopes the matches will bolster London's reputation as a magnet for international sport on the back of the successful staging of the 2012 Olympics and Paralympics.
He said: "London has staged an extraordinary year of sport and I want to ensure this is a springboard for even more world class sports spectaculars in the future.
"A second NFL game headed to the capital is fantastic news for sports fans and will help to inject tens of millions of pounds into the city's economy."
The NFL has played a regular-season game at Wembley in each of the last five years but this will be the first time that two games have been hosted in London in one season.
The Jaguars have agreed to play one home game in London each year from 2013 through to 2016.
Participation in amateur American football in the UK has risen over the past few years, growing by approximately 15 per cent per year since 2007, while television audiences for NFL games have risen 154 per cent since 2006.
Capacity crowds of 80,000 are expected to attend both Wembley matches, according to Johnson, whose London & Partners promotional agency has been working closely with the NFL to try to bring more games to London.