- Christopher Columbus arrives in Central America, specifically in what is now Honduras.
- Amerigo Vespucci explores the Caribbean coast of Central America.
1509:
- Spanish conquistadors led by Vasco Núñez de Balboa reach the Pacific Ocean after crossing the Isthmus of Panama.
1513:
- Balboa becomes the first European to explore the Pacific Ocean from the American continent.
1519:
- Hernán Cortés lands on the coast of what is now Mexico and begins the conquest of the Aztec Empire.
1524:
- Pedro de Alvarado, a lieutenant of Cortés, leads an expedition into Central America and conquers the Maya city-states of Iximché and Q'umarkaj.
1525:
- The Spanish found the city of San Miguel de Tegucigalpa (present-day Tegucigalpa, Honduras).
1527:
- The first African slaves are brought to Central America.
1530:
- The Spanish found the city of Santiago de los Caballeros de Guatemala (present-day Antigua Guatemala).
1539:
- The Franciscans arrive in Central America and begin to evangelize the indigenous people.
1542:
- The Dominican friar Bartolomé de las Casas arrives in Central America and begins his campaign to defend the rights of the indigenous people.
1549:
- The Spanish Crown passes the New Laws, which improve the treatment of the indigenous people.