The 2021 Major League Baseball season began on April 1, while the regular season ended on October 3. The postseason began on October 5. The World Series then began on October 26 and ended on November 2 with the Atlanta Braves defeating the Houston Astros in six games to win their second title since moving to Atlanta.
For the second consecutive year, cross-border travel restrictions due to the COVID-19 pandemic forced the Toronto Blue Jays to open their home schedule in the United States, with tenures in Dunedin, Florida, and Buffalo, New York. Later, the Canadian government granted an exemption to allow the Blue Jays to return to Rogers Centre in Toronto, Ontario, beginning July 30.
The 91st All-Star Game held on July 13 was supposed to be held at Truist Park, the home of the Braves, but league officials moved the game to Coors Field, home of the Colorado Rockies, following the passage of the Georgia Senate Bill 202 by the Georgia General Assembly, which MLB considered to be restrictive of voting rights.
This was the final season of the Cleveland Indians competing with that nickname. On December 14, 2020, the team announced that they would unveil their new moniker and associated uniform and stadium changes before the 2022 season to replace the 106-year-old nickname. On July 23, the Indians revealed that their new nickname would be the "Guardians", debuting the following season.