The Chicago Bears will face the Oakland Raiders in the first NFL match at the Tottenham Hotspur Stadium, the NFL confirmed on Wednesday.
Spurs' new home was purposely designed with an NFL field under the playing surface and the Bears and Raiders will get first use of the pitch.
A total of five regular season matches will be hosted outside the United States, with London hosting another three and the other in Mexico City.
The London schedule will kick off with an intriguing game between the Bears and the Raiders as Chicago will bring Khalil Mack overseas to play against the team that traded him out of Oakland, while the Raiders bring a new look to their roster with Antonio Brown.
Seven days later, the Carolina Panthers will face the Tampa Bay Buccaneers at the same venue in a match-up that will feature NFC South divisional rivals as Cam Newton and Jameis Winston square off.
Wembley will also host two matches as the Cincinnati Bengals meet the Los Angeles Rams, while the final match sees the Jacksonville Jaguars – complete with new quarterback Nick Foles - play the Tennessee Texans in an AFC South match-up.
The NFL will give a game in Mexico another shot after the Rams versus the Kansas City Chiefs was cancelled last season out of concern for player safety concerns due to field conditions.
This time the Chiefs will meet the Los Angeles Charges in mid-November at the Azteca Stadium.