Quarterback Alex Smith will lead the 49ers out at Wembley
The San Francisco 49ers and the Denver Broncos will play at Wembley Stadium on 31 October 2010, American's National Football League has confirmed.
The 49ers, officially the home team, are five-time NFL champions, while the Broncos have twice won the Super Bowl.
Wembley secured the game following the success of the previous three fixtures that have been held in London.
"We hope to have a second game this season and expect to know within a fortnight," NFL UK confirmed.
Following the success of the NFL's first trip to London in 2007 the league committed to three further games in the UK. The New England Patriots beat the Tampa Bay Buccaneers in front of an 84,254 crowd in last year's event.
"The 49ers organisation is excited to be part of the NFL's 2010 international schedule," said San Francisco 49ers president Jed York.
"The international games have been so well received in recent years that it will surely be an exciting experience for our players, coaches, staff and fans."
San Francisco, who regularly attract more than 69,000 fans to Candlestick Park Stadium, will give up a home game and act as hosts for the Wembley clash. Like the Broncos, they finished with an even record of eight wins and eight defeats in the 2009 season.
The 49ers are well-known in the UK because their success in the 1980s coincided with the sport enjoying a sustained period of popularity in Britain.
NFL at Wembley in 40 seconds
They won the Super Bowl at the end of the 1981, 1984, 1988, 1989 and 1994 seasons. The team has struggled in recent years though and have not appeared in the play-offs since 2002.
Denver have been more successful over the last decade, but the team has not appeared in the Super Bowl since legendary quarterback John Elway retired having led the team to victory over the Atlanta Falcons in the 1998 edition.
"It's a wonderful, historic opportunity for our franchise and will be an unforgettable experience for our players, coaches and fans," said Broncos president Pat Bowlen.
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