The home of English rugby Twickenham will host its first NFL game in October next year, it was announced on Wednesday.
The St Louis Rams will face a team from the NFC East on October 23 with their opponents to be determined based on the final standings in that division.
Earlier this month the NFL and Rugby Football Union unveiled a partnership which will see Twickenham host at least three regular-season games over the next three years.
The 2016 International Series will also see the Jacksonville Jaguars return to London for a fourth consecutive year with a game against the Indianapolis Colts scheduled for October 2, while the Cincinnati Bengals will play the Washington Redskins on October 30.
The NFL has enjoyed great success in staging matches at London's Wembley and recently extended its agreement with the stadium, with a minimum of two games per year to be played there through to 2020.
The English capital will also play host to regular-season games at Tottenham's new stadium from 2018.
NFL commissioner Roger Goodell said: "The passion our UK fans have shown for the NFL is overwhelming.
"We are very appreciative of the strong and growing fan support, not only for the games, but for all of the related NFL events we host in the UK throughout the year.
"We look forward to welcoming new fans to their first NFL game in 2016 and welcoming back thousands of others that are helping our sport grow to new levels of popularity in London and beyond."
The game times and a possible additional International Series game outside of the UK will be announced at a later date, the NFL added.