The 2012 Major League Baseball season began on April 5 because during the MLB Spring Training it was the first of a two-game series between the Seattle Mariners and the Oakland Athletics at the Tokyo Dome in Japan. On November 22, 2011, a new contract between Major League Baseball and its players union was ratified, and as a result, an expanded playoff format adding two clubs would be adopted no later than 2013 according to the new Collective Bargaining Agreement. The new format of the 2012 postseason to used the 1 game series of the Wild Card round of the format for the 2012 postseason only. The restriction against divisional rivals playing against each other in the Division Series round that had existed in previous years was eliminated, as the Baltimore Orioles and New York Yankees squared off in one of the best-of-five LDS in the American League. On April 4, 2012, it was the last day of the MLB Spring Training and ended with the new Marlins Park, as the newly renamed Miami Marlins hosted the defending World Series champion St. Louis Cardinals. The regular season ended on Wednesday, October 3. The entire master schedule was released on September 14, 2011.

Tokyo Dome is an indoor stadium in Bunkyo, Tokyo, Japan. It was designed as a baseball stadium following its predecessor, Korakuen Stadium. In Japan, it is often used as a unit of size; for example, "the new construction is five times the size of Tokyo Dome."