"We are bringing you one of the best rivalries in baseball," MLB commissioner Rob Manfred said Tuesday.
Boston will be the home team on June 29 and 30, 2019, for MLB's first games in Europe. The stadium will have a capacity of 55,000 in a baseball configuration.
MLB said it is also "committed to playing in London in 2020 and our intention is to establish a long-term footprint in the city" as American pro sports leagues continue to attempt to expand their reach to British fans.
The NFL has played regular-season games in London since 2007, holding 18 games at Wembley Stadium and three at Twickenham Stadium. Three more NFL games are scheduled for this year, including one at Tottenham's new stadium.
The NBA and NHL have also held regular-season games in London.
"The stadium infrastructure in this city gives Major League Baseball every opportunity to put on a first-class event," Manfred said. "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."
MLB has put renewed emphasis on international games since Manfred became commissioner in 2015.
Cleveland and Minnesota played a two-game series last month in San Juan, Puerto Rico, and San Diego and the Los Angeles Dodgers played in a three-game series in Monterrey, Mexico, last week. MLB announced Tuesday that Oakland and Seattle will open next season at the Tokyo Dome on March 20 and 21.