Interleague play is the term used to describe regular season Major League Baseball games played between teams in different leagues, introduced in 1997. Before the 1997 season, teams in the American League and National League did not meet during the regular season. AL/NL matchups only occurred during spring training, the All-Star Game, other exhibition games such as the Hall of Fame Game in Cooperstown, New York, and the World Series. Unlike modern interleague play, none of these contests, except for the World Series, counted toward official team or league records.

Interleague or interconference matchups have long been the norm in other professional sports leagues such as the NFL. Regular season interleague play was discussed for baseball's major leagues as early as the 1930s. In December 1956, Major League owners considered a proposal by Cleveland general manager and minority-owner Hank Greenberg to implement limited interleague play beginning in 1958. Under Greenberg's proposal, each team would continue to play a 154-game season, with 126 within that team's league, and 28 against the eight clubs in the other league. The interleague games would be played immediately following the All-Star Game. Notably, under Greenberg's proposal, all results would count in regular season game standings and league statistics. While this proposal was not adopted, the current system shares many elements. Bill Veeck predicted in 1963 that Major League Baseball would someday have interleague play. While the concept was again considered in the 1970s, it was not implemented until the 1990s, at least in part as an effort to renew the public's interest in MLB following the 1994 players' strike.