The "Legend Series" will be played at Rod Carew Stadium in Panama City on March 15-16 and will honor former Yankees great Mariano Rivera of Panama, MLB's all-times saves leader, who retired at the end of the 2013 season.
Panama has long been a breeding ground for baseball talent, producing 40 MLB players over the years, including four currently on major league rosters.
"As long as I can remember, it has been my dream to bring my team, the Yankees, to play baseball in Panama," Rivera said in a statement.
"I grew up playing in Puerto Caimito, where I developed my passion for baseball and began a journey that brought me to New York. It is my hope that this legacy series will inspire other young players to pursue their dreams."
MLB has increasingly eyed international markets over the past two decades, and will start the 2014 season with two regular season games between the Los Angeles Dodgers and Arizona Diamondbacks in Sydney, Australia, on March 22-23.