• March 4 - Hernan Cortes lands in Mexico
• Charles I of Spain becomes Emperor of Holy Roman Empire as Charles V, Holy Roman Emperor (ruled until 1556)
• Erasmus publishes his Colloquia[?]
• Martin Luther questions the infallibility of papal decrees
• Mannerism, artistic form appears in Italy and spreads
• Spaniard Hernando Cortes enters Tenochtitlan, the capital of the Mexican Aztec Empire
• Ferdinand Magellan (1480-1521) leaves Europe to circumnavigate the world (September 20th[?]

Births

• King Henri II of France (d.1559)
• April 13 - Catherine de Medici, queen of France

Deaths

• January 12 - Maximilian I, Holy Roman Emperor
• January 21 - Vasco Nuñez de Balboa, Spanish explorer
• August 11: Johann Tetzel
• Lucrezia Borgia, daughter of Rodrigo Borgia (b.1480)
• Leonardo da Vinci, inventor, painter and genius (b. 1452)
• Holy Roman Empire Emperor Maximilian I (b. 1459)