- January 1 - French troops surrender Gaeta to the Spanish under Cordoba.
- January 31 - France cedes Naples to Aragon
- Michelangelo Buonarroti finishes his sculpture of David.
- Moldavia, Stephan IIIrd the great fights against Turkey and Poland.
- Baber besieges and captures Kabul.
- Ferdinand II of Aragon becomes King of Naples as Ferdinand III.
- Christopher Columbus return to spain from his fourth voyage where he and his yonger son, Ferdinand, explored the coast of Central America from Belize to Panama.
- Aldo Manuzio publishes Demosthenes.
- Heinrich Bullinger, Swiss reformer.
- Michele Ghislieri, becomes Pope Pius V in 1566.
- Matthew Parker, becomes Archbishop of Canterbury in 1559.
- November 26 - Isabella of Castile, Queen of Castile, the wife of Ferdinand II of Aragon, the mother of Catherine of Aragon, and the patron of Christopher Columbus.
- Philibert II of Savoy, Duke of Savoy
- Domenico Maria Novara da Ferrara, Astronomer and teacher of Nicolaus Copernicus
- Thomas Stanley, 1st Earl of Derby