Next year's game, to be played on September 29 2013, will precede the already scheduled October 27 contest between the San Francisco 49ers and Jacksonville Jaguars, both games part of the NFL's International Series.
As part of the series, the league has been playing one regular-season contest a year in London since the 2007 season.
This year's clash is slated for October 28 when the New England Patriots are due to face the St. Louis Rams.
Now 2013 will mark the first time the league has included two regular-season overseas games.
"Since we started playing regular-season games in London five years ago, we have heard very clearly from our UK fans — they want more football," said NFL Commissioner Roger Goodell at the league's Fall Meeting in Chicago.
"We are excited to play two games in London and take this next step in the growth of our game. We believe that more football will lead to more fans."
The five previous games held in London have drawn crowds from about 76,000 to over 84,000 spectators.
The NFL has committed to playing at least once a year in London through 2016, with the Jaguars serving as the host team for a game in each of the next four seasons.
Meanwhile NFL owners have approved the sale of the Cleveland Browns.
New majority owner Jimmy Haslam immediately said Mike Holmgren would be replaced as team president, with former Philadelphia Eagles president Joe Banner taking on the role of the Browns' chief executive officer.
Holmgren will stay with the club until the end of the season to smooth the transition, Haslam said.
"With us coming in and taking a more active role, Mike has decided at the end of the year to leave the Cleveland Browns and retire," Haslam said. "Mike will work closely with us over the next four months to make this transition as easy as possible."
Haslam's group purchased 70 per cent of the franchise from Randy Lerner in early August, reportedly for a price of more than $1 billion (Dh3.67bn).