- Jan 25 Battle at Talikota, India: Deccan sultanate destroys Vijayanagar's army and the last Hindu kingdom of Southern India
- Mar 1 Portuguese soldier Estácio de Sá founds the city of Rio de Janeiro, Brazil
- Mar 22 Turkish Armada leaves Constantinople bound for the siege of Malta with about 193 ships
- Apr 27 First Spanish settlement in the Philippines founded at Cebu City
- May 18 Turkish Armada arrives to begin the Great Siege of Malta, aiming to establish the island as their gateway for the conquest of Europe
- Jun 14 Catharina de Medici and Duke of Alva discuss Calvinism
- Jun 17 Matsunaga Hisahide assassinates the 13th Ashikaga shogun, Ashikaga Yoshiteru
- Jun 23 Turgut Reis [Dragut], commander of the Ottoman Navy, dies during the Siege of Malta
- Sep 8 1st permanent European settlement in the US founded at St. Augustine, Florida
- Sep 8 Turkish siege of Malta broken by Maltese & Knights of St John
- Sep 20 Spaniards capture Fort Caroline Florida & massacre the French
- Nov 13 Pope Pius IV publishes decree Professi fidei
- Dec 24 Compromise of the Nobles in Habsburg Netherlands closes against inquisition
Gregory I
Gregory XIII
Julius II
Julius III
Leo X
Pius V