The NFL has staged games in London every year since 2007, and last Sunday the New England Patriots beat the St Louis Rams 45-7 in front of a sold-out Wembley crowd that included Johnson.
Next year, Wembley will host two NFL games and the north London stadium has an exclusive deal to host the International Series games until 2016.
But Johnson, who is chairman of the London Legacy Development Corporation responsible for deciding how the Olympic Stadium will be used in the future, wants to see if there is a role for the Stratford venue.
A spokesman for the Mayor said in a statement: "Sunday's game at Wembley, in front of over 80,000 fans, further cements London's reputation as the natural home of American Football outside of the United States.
"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.
"Given the ever growing popularity of Gridiron on 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 involving the NFL and London.
"The talks were exploratory, we are at an early stage, but the signs are encouraging."
The Mayor's office are exploring the long-term possibility of utilising the Olympic Stadium to bring more games to London, potentially in addition to Wembley.
One prospect often discussed is whether London could be the base for a new NFL franchise.
A decision on the future use of the Olympic Stadium is not expected before December.
West Ham are one of those interested in moving into the venue, which will retain a running track.