Tottenham Hotspur's new 61,000-seat stadium will host an NFL game for the first time when the Seattle Seahawks play the Oakland Raiders on 14 October.
It will be played on the stadium's artificial surface, which sits beneath the retractable grass pitch.
Premier League side Spurs are due in their new home for the 2018-19 season.
Tottenham chairman Daniel Levy said at the International Series launch: "We hope there is a franchise in London and we want this stadium to be its base."
The club have a 10-year deal with the NFL to stage two games a season.
Wembley Stadium will host the Philadelphia Eagles against the Jacksonville Jaguars and the Tennessee Titans versus the LA Chargers later in October.
One of those fixtures will be played on 21 October and the other on 28 October, with the decision on that still to be taken.
Is a London franchise any closer?
Since the NFL started playing games in London in 2007 the idea of having a team based in the city has gained traction.
The league's executive vice-president for international, Mark Waller, says that unlike other American sports, such as basketball, his sport could make it work.
"The beauty of our season is that we play once a week and we only play 16 games. We are able to contemplate something as audacious as having a team in London.
"For the NBA, with the number of games it has and the number that are played on consecutive days, it would be physically impossible to contemplate putting a team in the UK."
Will White Hart Lane be ready?
Tottenham Hotspur's new stadium is still being built but the club's chairman Daniel Levy is confident the ground will be ready in time.
"It is very exciting," said Levy. "[When I] first went to see Mark he thought I wasn't thinking straight.
"Subject to unforeseen circumstances I am very confident sitting here today that the season we are about to enter into, we will be playing our games here - from the start of the season."