Centuries: 15th century - 16th century - 17th century
- April 22 - Battle of Bicocca - French and Swiss forces under Odet de Lautrec are defeated by the Spanish in their attempt to retake Milan, and are forced to withdraw into Venetian territory.
- July 28 - Beginning of Ottoman Sultan Suleiman I's siege of the Knights of St. John in Rhodes.
- September 6 - The Vittoria, one of the surviving ships of Ferdinand Magellan's expedition, returns to Sanlcar de Barrameda in Spain, becoming the first ship to circumnavigate the world.
- December 18 - The Turks finally break into Rhodes, but the Knights continue fierce resistance in the streets
- December 20 - Suleiman the Magnificent accepts the surrender of the surviving Knights, who are allowed to evacuate. They eventually re-settle on Malta and become known as the Knights of Malta.
- First Diet of Nuremberg
- Adrian Dedens becomes Pope Adrian VI