Each season consists of 162 games (with an additional game, or games, in case of a tie breaker needed to determine postseason participation), which generally begins on the first Sunday in April and ends on the first Sunday in October, with the postseason played in October and sometimes into early November. The same rules and regulations are played between the two leagues with one exception: the American League operates under the Designated Hitter Rule, while the National League does not. Utilization of the DH Rule in interleague play, the All-Star and World Series games is determined by the home team's league rules.

MLB is controlled by the Major League Baseball Constitution that has undergone several incarnations since 1876 with the most recent revisions being made in 2005. Under the direction of Commissioner of Baseball (currently Bud Selig), Major League Baseball hires and maintains the sport's umpiring crews, and negotiates marketing, labor, and television contracts. As is the case for most of the sports leagues in the United States and Canada, the "closed shop" aspect of MLB effectively prevents the yearly promotion and relegation of teams into and out of the Major League by virtue of their performance. Major League Baseball maintains a unique, controlling relationship over the sport, including most aspects of minor league baseball. This is due in large part to a 1922 U.S. Supreme Court ruling in Federal Baseball Club v. National League, which held that baseball is not interstate commerce and therefore not subject to federal antitrust law. This ruling has been weakened only slightly in subsequent years.

The production/multimedia wing of MLB is New York-based MLB Advanced Media, which oversees MLB.com and all 30 of the individual teams' websites. Its charter states that MLB Advanced Media holds editorial independence from the League itself, but it is indeed under the same ownership group and revenue-sharing plan. MLB Productions is a similarly-structured wing of the league, focusing on video and traditional broadcast media.

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