The stadium will have a capacity of 55,000 in a baseball configuration.
The Red Sox and Yankees are now the best two teams in the Major League Baseball, with 25 and 24 wins respectively.
Major League Baseball is set to emulate the NFL as of next year and set up shop in London.
However, the venue has faced legacy concerns with London Mayor Sadiq Khan taking personal charge of the stadium's future following Newham Council's exit from ownership company E20 late previous year.
"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".More news: Joe Burrow To Transfer From Ohio State
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"The stadium infrastructure in this city gives Major League Baseball every opportunity to put on a first-class event", Manfred added.
Manfred said: "We are bringing you one of the best rivalries in baseball".
It has already been announced that Oakland and Seattle will play next season's opener at the Tokyo Dome on March 20-21. There were significant challenges that had to be overcome. This series will surely be the most significant worldwide event to date for Major League ball. "So we understand there will be a lot of excitement around it", said Yankees manager Aaron Boone on Sunday. "We expect an exciting and intense pair of games and appreciate the significance of representing our sport in such a meaningful way".
Khan said: "London is the sporting capital of the world. That fact, coupled with the nature of the rivalry and our desire to make the most out of the London series, made this the ideal choice for the London outing".
"Look, Red Sox-Yankees is always big, and obviously they're a great team".
Boston Red Sox joint owner John W Henry.