The London Stadium will have a 55,000 capacity for the games but Henry believes Londoners will struggle to secure tickets.
A two-year deal has been agreed that will include another series in London in 2020, with participating teams to be announced, and other initiatives that will aim to establish a footprint in the city.
One of the fiercest rivalries in sport - the New York Yankees versus the Boston Red Sox - is on the move and heading to London as Major League Baseball flies across the Atlantic to broaden its global reach.
The NFL has played regular-season games in London since 2007, holding 18 games at Wembley and three at Twickenham. "All the hard work has paid off".
Boston Red Sox Principal Owner John W. Henry, whose Fenway Sports Group owns Champions League finalists Liverpool, said: "For several years the Red Sox and Yankees have discussed playing in London as the first-ever Major League Baseball regular season game in Europe".
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Mr Khan has said he wants to make London the sporting capital of the world.
"It's also the first time the Red Sox and Yankees have played one another outside of NY or Boston", added Henry, who also co-owns English Premier League side Liverpool. There were significant challenges that had to be overcome. Two of the most recognizable teams are once again two of the best.
Red Sox principal owner John Henry, who also owns Liverpool FC of the Premier League, said that Boston and NY have been talking about playing overseas for some time.
"London was a target for us regardless of either football or basketball", Manfred was quoted as saying by the London Evening Standard. "I can't wait to hear someone shout "play ball" at London Stadium".
"As a venue, we are immensely proud to be hosting MLB's London Series at London Stadium in 2019", said Graham Gilmore, CEO of London Stadium 185. Located in the eastern part of the capital, the stadium is now home of Premier League club West Ham United and was also used during the 2015 Rugby World Cup and the 2017 Athletics World Championships. "That fact, coupled with the nature of the rivalry and our desire to make the most out of the London series, made this the flawless choice for the London outing".