On June 21, the following notable historical events related to Missouri have been recorded:

• 1818: The steamboat Independence became one of the first to navigate the Missouri River, reaching Franklin, Missouri, around this date. This marked a significant advancement in transportation and commerce for the Missouri Territory, boosting settlement and trade.
• 1861: During the Civil War, pro-Union and pro-Confederate factions in Missouri were engaged in ongoing tensions. While no specific battle occurred on June 21, this date falls within the period of the "Camp Jackson Affair" aftermath, where St. Louis was a focal point of conflict between Union forces and secessionist militias.
• 2004: The St. Louis Cardinals played a notable game against the Chicago Cubs at Busch Stadium, with Albert Pujols hitting a key home run, contributing to a Cardinals victory. This game was part of their successful 2004 season, which saw them reach the World Series.