Premier League side West Ham United have long sought a move to the site, but the growing popularity of American football in the UK has increased speculation that the league might look to base a team in London.
Over 84,000 people packed into Wembley last weekend to watch the New England Patriots defeat the St. Louis Rams – the sixth year in succession that a regular season NFL game has sold out in the British capital.
There will be two games played at Wembley next season but something more permanent could now be in the pipeline according to the Daily Telegraph.
The paper quotes a spokesperson for the mayor as saying: "Given the ever-growing popularity of gridiron this side of the Atlantic, the mayor and his team have held a number of meetings with senior executives in the last few days to explore further opportunities for NFL in London.
"The talks were exploratory and we are at an early stage but the signs are encouraging.”
Mayor Johnson is the chairman of the London Legacy Development Corporation - the company that is responsible for the running of the Olympic Stadium.
The paper reports that West Ham's bid has been hampered by the fact that they would be reluctant to pay the estimated £200m needed for the installation of retractable seating under the stadium’s athletics track and would instead look for state aid to help make the modifications.
Another factor in the NFL's favour is that a team would only need the stadium for a maximum of 10 times a season, which would allow other speculated events – such as a rumoured Formula One race – to take place at the venue.
The mayor's spokesperson noted: “Sunday’s game at Wembley, in front of more than 80,000 fans, further cements London’s reputation as the natural home of American football outside of the US.
"Only last week the mayor, in conjunction with the NFL, announced an expansion from one to two regular-season matches in London from 2013. That means in total an additional £44 million in revenue for the capital from next year."
Robert Kraft, the owner of the New England Patriots, also backed the idea of a London team when over last weekend.
"For our game to continue to grow and be special we have to expand our fan base, and I think from our cultural and language point of view, going to England and playing there and developing the game made sense," he told the Boston Globe.
"We have such a following in the UK and people really grab on to the game. It’s wonderful to see another country embrace our sport, and by bringing the real game there I think they have really loved it.”