The match is still to be confirmed but is likely to be a home game for the Miami Dolphins against the New York Giants.
NFL commissioner Roger Goodell said: “There is no better place to begin this initiative than London.
“It is one of the great cities of the world with an established and growing fan base for our game.”
The decision follows an agreement in October to play up to two games outside the US every season for the next five years.
Official confirmation Wembley will be the venue is still to be made with Twickenham also believed to be a possible option.
