Stars like Eli Manning will play the full game at Wembley
Miami Dolphins v NY Giants
Sunday 28 October, 1700 GMT
Highlights: 2300-2350, BBC TWO and the BBC website (UK users only)
Back in 1986, William "Refrigerator" Perry rumbled onto the hallowed turf of Wembley Stadium with the popularity of the NFL at its height.
Millions watched American football in its weekly Sunday teatime slot, and many knew the identities of Perry's Chicago Bears team-mates too.
But Premier League football and professional rugby gradually eclipsed American football for popularity through the 1990s to the degree where many people who hear the term think it is the sport David Beckham plays.
To gain a new generation of fans, the NFL has stepped up a gear. For the first time, a top-tier game in the UK counts.
When the Bears played the Dallas Cowboys in front of the old twin towers 21 years ago, it was in a pre-season exhibition game, just a tune-up for the real action to come.
This time, the Miami Dolphins and New York Giants will see the result reflected in their league standing in the first competitive NFL game ever played outside the Americas.
This time it is live; this counts in America and for the teams that are playing it
Former Miami linebacker
Former linebacker John Offerdahl played for the Dolphins against the San Francisco 49ers in another "American Bowl" pre-season game at Wembley in 1988.
He and fellow stars like quarterback Dan Marino only played a small part before coaches took a look at their reserve players.
Offerdahl told BBC Sport: "Because it was an exhibition after one or two series all the good players were off and the Brits were saying, 'Hey, this stinks!'
"This time it is live; this counts in America and for the teams that are playing it, and I think it's about time that the NFL brought real games international."
This time, some of the game's biggest stars, like quarterback Eli Manning and tight end Jeremy Shockey of the Giants and defensive end Jason Taylor of the Dolphins, will duel into the final minutes.
Anyone suggesting there is no interest in American football in the UK didn't battle for tickets to the Wembley game when they went on sale. The 90,000-seat stadium could have been sold out two or three times.
I would anticipate that we will be back here in London on a regular basis
NFL commissioner Roger Goodell is so pleased by the response he is already planning for more games in London.
"The owners approved two regular season games per year [abroad] and this has been a tremendous success even before the game's been played," he told BBC Sport.
"I would anticipate that we will be back here on a regular basis."
Goodell has also hinted the NFL's showpiece game, the Super Bowl, could be played at Wembley in future but that would not be before 2011, as sites are already fixed until then.
The NFL's motives are clear - to expand its fan base further, increasing television revenues and merchandise sales.
But as well as bringing one of its biggest games to Europe, the league has built on its youth development programmes, looking to spot talent and to increase interest among youngsters.
Londoner Gerry Anderson, who played for the London Monarchs in the now-defunct NFL Europe league in the early 1990s, is now a development officer for the NFL in the UK.
It will make my job easier because now kids are going to be able to identify American football and know what it's about
British NFL development officer
It is his job to go into schools and spread the gospel of American football to young people who may never have heard of the game.
"For most of them you've got to start from scratch because they just don't know. They're used to soccer. American football's a new sport for them," he told BBC Sport.
Anderson is a coach with the London Warriors urban American football programme, which involves around 120 players from the age of eight to 18 in South London.
He is very much looking forward to Sunday's game and the effect it will have on the country.
"The impact is going to be huge. It will make my job easier because now kids are going to be able to identify American football and know what it's about.
"I'm hoping it will make them aware there's an opportunity to play American football in the UK."
Part of Anderson's job is introducing scaled-down versions of the game, like flag football for younger players, which has no padding or tackling.
"I started at the age of 20, like most players at the time," said the former tight end.
"Now there are young players and programmes that have kids as young as eight or nine.
"The NFL has been trying to push the grassroots development and get people interested because if you don't know American football you won't watch it on TV because you don't understand it."
The men on the sidelines on Sunday will not be thinking about the wider implications, though. They must deal with the implications of a lengthy flight, arriving 56 hours before kick-off, and jet lag after moving five time zones.
"There's no doubt it will affect them. Just being in a different culture will affect them," said Offerdahl.
"But it's an experience for them, it's equal for both teams and it's a show.
"It will be interesting to see which team can assimilate to the environment and the culture and play well."
The Giants, who have won five consecutive games since losing their opening two, will be keen to retain that momentum and avoid the sort of late-season meltdown they suffered last year.
The Dolphins have lost seven games in seven for their worst start to a season in their 42-year history. They need to pull something out of the bag with an injury-ravaged team.
Offerdahl played in the last great Miami team, whose Super Bowl defeats in 1983 and '85 were some of the first games watched by a UK television audience.
But he admits that, more than 20 years on, the Florida side are struggling.
"We're looking for anything!" he said.
"We're hoping that in the UK we can get a fresh sense of new life."
Sunday's match is certainly a fresh departure for the NFL itself, and a massive boost for its British fans.