The new Tottenham Hotspur Stadium will host its first NFL game when the Chicago Bears play the Oakland Raiders on 6 October.
The £1bn multi-purpose venue, which opened earlier this month, will also welcome the Carolina Panthers and Tampa Bay Buccaneers on 13 October.
Wembley Stadium stages two games, including 2018 Super Bowl runners-up the LA Rams against the Cincinnati Bengals.
The NFL season starts on 5 September.
The Tottenham Hotspur Stadium opened on 3 April for the club's Premier League match against Crystal Palace.
The 62,062-seater arena was due to host its first NFL game in 2018 as part of a 10-year agreement with the league, only for it to be switched to Wembley because of delays in its construction.
The NFL's International Series concludes on 18 November with a game between the Kansas City Chiefs and the Los Angeles Chargers at Mexico City's Azteca Stadium.
NFL International Series fixtures
Tottenham Hotspur Stadium
Sunday, 6 October - Chicago Bears v Oakland Raiders (18:00 BST)
Sunday, 13 October - Carolina Panthers v Tampa Bay Buccaneers (14:30 BST)
Sunday, 27 October - Cincinnati Bengals v LA Rams (17:00 GMT)
Sunday, 3 November - Houston Texans v Jacksonville Jaguars (14:30 GMT)
Monday, 18 November - Kansas City Chiefs v Los Angeles Chargers (01:15 GMT Tuesday)