"We hope this series will be the beginning of a relationship with London that persists and a continuation of increasing exposure for Major League Baseball in Europe". The Red Sox will be the home team, not that it really matters.
Manfred said: "We are bringing you one of the best rivalries in baseball".
The 2019 matches are set for June 29-30, with the Red Sox designated as the home team, in what will be the first regular-season Major League Baseball fixtures staged in Europe.
With a two-year deal agreed upon, Major League Baseball will host an additional series in London in 2020, with those teams to be announced later.
The league has, however, played games in Mexico, Japan, Puerto Rico and Australia.
Baseball commissioner Robert Manfred described the plan as "our most significant endeavor in Europe", while Tony Clark, executive director of the players' association, MLBPA, said fans should expect intense competition.
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"They are excited about the chance to meet new fans, and showcase the game they love. This is a major coup demonstrating, once again, that London is the sporting capital of the world and I am excited about a new partnership with MLB and the long term future of this sport in our great city".
Both the Red Sox and Yankees have played games on worldwide soil in recent years, visiting the Tokyo Dome for season openers.
"We could not be happier that Commissioner Manfred has been able to make this a reality", Red Sox owner John Henry said. "I can't wait to hear someone shout "play ball" at London Stadium", he added.
That the Sox and Yankees were chosen is a testament to their rivalry's resurgence.
London already has a strong presence in both the National Football League and NBA.