London will host four NFL games in 2019 with two to be played at Tottenham's new stadium and two at Wembley.
Spurs' new 62,000-seat arena was in line to host the fixture between Seattle Seahawks and Oakland Raiders in October but has yet to open.
Wembley, which staged three sold-out NFL games in recent weeks, will host the remaining two games next year.
"London is the world's sporting capital," said Mayor of London Sadiq Khan.
"Hosting NFL matches here is fantastic for fans of American football in the UK as well as supporters from all over Europe."
Next year's fixtures will bring the total number of NFL games played in London to 28 since the first match in 2007.
Only three of the NFL's 32 teams have not played in the city.
Sports minister Tracey Crouch said: "The League brings an incredible Super Bowl-style atmosphere to the UK, with fans sporting jerseys from a range of NFL teams packing out Wembley this autumn in record numbers.
"I am sure the two games at Tottenham next year will also be a huge success as the UK will once again show its passion and enthusiasm for this fantastic sport."