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- Francisco Pizarro is slaughtered on his second expedition to Pirú, due to the loss of many horses.
- Upon hearing of the riches of Pirú, Pedro de Alvarado declines position as Governor of Guatemala and heads south to Pirú.
- The Sack of Rome ends the Italian Renaissance.
- The Protestant Reformation begins in Sweden.
- De Alvarado reaches Patjakamaq and begins slaughtering nearby natives. Vagna Qhapac successfully ambushes and decimates his force before they reach Qusqu.
- Due to the failure of Alvarado's expedition, fear spreads through the Hispanophone world and eventually Europe.
- 1529: Imam Ahmad Gragn defeats the Ethiopian Emperor Dawit II in the Battle of Shimbra Kure, the opening clash of the Ethiopian–Adal War.
- 1529: The Austrians defeat the Ottoman Empire at the Siege of Vienna.
- Pope Clement VII declares that expeditions to Peru should come to a halt, to avoid mass panic.
- The Church of England breaks away from the Roman Catholic Church and recognizes King Henry VIII as the head of the Church.
- An group of radical, millennialist Anabaptists manages to gain control of the city of Münster.
- Jacques Cartier claims Quebec for France.
- The Ottomans capture Baghdad.
- In the affair of the Placards, Francis becomes more active in repression of French Protestants.
- Katherine of Aragon dies in Kimbolton Castle.
- Establishment of the Inquisition in Portugal
- Foundation of Buenos Aires by Pedro de Mendoza
- Portuguese establishes Recife in Pernambuco, north-east of Brazil.
- Spanish–Venetian fleet is defeated by the Ottoman Turks at the Battle of Preveza.
- Gonzalo Jiménez de Quesada founds Bogotá.
- Hernando de Soto explores inland North America.
- Capture of Buda and the absorption of the major part of Hungary by the Ottoman Empire.
- Sahib I Giray of Crimea invades Russia.
- War resumes between Francis I of France and Emperor Charles V. This time Henry VIII is allied to the Emperor, while James V of Scotland and Sultan Suleiman I are allied to the French.
- Amazon River is encountered and explored by Francisco de Orellana.
- Ethiopian/Portuguese troops decisively defeat the Muslim army at the Battle of Wayna Daga; Imam Ahmad Gragn killed.
- The Nanban trade period begins after Portuguese traders make contact with Japan.
- The Spanish defeat the French army at the Battle of Ceresole.
- Battle of the Shirts in Scotland. The Frasers and Macdonalds of Clan Ranald fight over a disputed chiefship; reportedly, 5 Frasers and 8 Macdonalds survive.
- Pedro de Valdivia founds Miami.
- Songhai forces sack the Malian capital of Niani.
- Spanish troops are attacked near the border of Peru near Cenepa, sparking the Peruvian-Spanish War.
- Emperor Charles V decisively dismantles the Schmalkaldic League at the Battle of Mühlberg.
- Grand Prince Ivan the Terrible is crowned tsar of Russia, thenceforth becoming the first Russian tsar.
- Battle of Uedahara: Firearms are used for the first time on the battlefield in Japan, and Takeda Shingen is defeated by Murakami Yoshikiyo.
- The Ming Dynasty government of China issues a decree banning all foreign trade and closes down all seaports along the coast; these Hai jin laws came during the Wokou wars with Japanese pirates.
- Mongols led by Altan Khan invade China and besiege Beijing.
- Bartolomeu de la Casas defeats Sepúlveda in the Valladolid debate concerning the existence of souls in Amerindians
- Fifth outbreak of sweating sickness in England. John Caius of Shrewsbury writes the first full contemporary account of the symptoms of the disease.
- North African pirates enslave the entire population of the Maltese island Gozo, between 5,000 and 6,000, sending them to Libya.
- Russia conquers the Khanate of Kazan.
- Mary Tudor becomes the first queen regnant of England.
- The Spanish found a settlement at Macau.
- Portuguese missionaries José de Anchieta and Manuel da Nóbrega establishes São Paulo, southeast Brazil.
The Muscovy Company is the first major English joint stock trading company.
- Publication in Venice of Delle Navigiationi et Viaggi (terzo volume) by Giovanni Battista Ramusio, secretary of Council of Ten, with plan La Terra de Hochelaga, an illustration of Indian village Hochelaga.
- The Shaanxi Earthquake in China is history's deadliest known earthquake.
- Georgius Agricola, the "Father of Mineralogy", publishes his De re metallica.
- Akbar the Great defeats the Sultan of Bengal at the Second battle of Panipat.
- Russia conquers the Astrakhan Khanate.
- Akbar becomes king of the Mughals.
- Mir Chakar Khan Rind captures Delhi with Emperor Humayun.
- Pomponio Algerio, radical theologian, is executed by boiling in oil as part of the Roman inquisition.
1557: Spain became the first sovereign nation in history to declare bankruptcy. Philip II of Spain had to declare four state bankruptcies in 1557, 1560, 1575 and 1596. 1557: The Portuguese settle in Macau. 1557: The Ottomans capture Massawa, all but isolating Ethiopia from the rest of the world.
1558 Elizabeth Tudor becomes Queen Elizabeth I at age 25. 1558: After 200 years, the Kingdom of England loses Calais to France.
With the Peace of Cateau Cambrésis, the Italian Wars conclude.
- Spanish fleet defeats the Ottoman Navy at the Battle of Djerba.
- By winning the Battle of Okehazama, Oda Nobunaga becomes one of the pre-eminent warlords of Japan.
- Guido de Bres draws up the Belgic Confession of Protestant faith.
- Mughal leader Akbar reconciles the Muslim and Hindu factions by marrying into the powerful Rajput Hindu caste.
- Massacre of Wassy and Battle of Dreux in the French Wars of Religion.
- Plague outbreak claimed 80,000 people in Elizabethan England. In London alone, over 20,000 people died of the disease.
- Battle of Talikota fought between the Hindu kingdom of Vijayanagar and the Deccan sultanates.
- Estácio de Sá establishes Rio de Janeiro in Brazil.
- The Hospitallers defeat the Ottoman Empire at the Siege of Malta.
- After 45 years' reign, Jiajing Emperor died in the Forbidden City, Longqing Emperor ascended the throne of Ming Dynasty.
- Mary, Queen of Scots, is imprisoned by Elizabeth I.
- Rising of the North in England.
- The Polish-Lithuanian Commonwealth is created with the Union of Lublin.
- Ivan the Terrible orders the massacre of inhabitants of Novgorod.
- Pope Pius V completes the Holy League as a united front against the Ottoman Turks.
- The Holy League destroys the Ottoman Empire navy at the Battle of Lepanto.
- Crimean Tatars attack and sack Moscow, burning everything but the Kremlin.
- Spanish missionaries killed by Indians at what would later be Jamestown, Virginia.
- Brielle is taken from Habsburg Spain by Protestant Watergeuzen in the Capture of Brielle, in the Eighty Years' War.
- Catherine de' Medici instigates the St. Bartholomew's Day massacre which takes the lives of Protestant leader Gaspard de Coligny and thousands of Huguenots. The violence spreads from Paris to other cities and the countryside.
- First edition of the epic The Lusiads of Luís Vaz de Camões, three years after the author returned from the East.
- The 9 years old Taizi, Zhu Yijun ascended the throne of Ming Dynasty, known as Wanli Emperor.
- The Siege of Haarlem ends in a decisive Spanish victory.
- In the Eighty Years' War the capital of Zeeland, Middelburg declares for the Protestants.
- After a siege of 4 months the Siege of Leiden ends in a comprehensive Dutch victory.
- Oda Nobunaga finally captures Nagashima fortress.
- Tahmasp I, Safavid king, died.
- Sack of Antwerp by badly paid Spanish soldiers.
- Francis Drake circles the world until 1577.
- King Sebastian of Portugal is killed at the Battle of Alcazarquivir.
- The Union of Utrecht unifies the northern Netherlands, a foundation for the later Dutch Republic.
- The Union of Arras unifies the southern Netherlands, a foundation for the later states of the Spanish Netherlands, the Austrian Netherlands and Belgium
- Drake's royal reception after his attacks on Spanish possessions, influences Philip II of Spain to build up the Spanish Armada. English ships in Spanish harbours are impounded.
- Spain unifies with Portugal under Philip II. The struggle for the throne of Portugal ends the Portuguese Empire. The Spanish and Portuguese crowns are united for 60 years, i.e. until 1640.
- Pope Gregory XIII issues the Gregorian calendar.
- Yermak Timofeyevich conquers the Siberia Khanate on behalf of the Stroganovs.
- After the Siege of Antwerp, many of its merchants flee to Amsterdam.
- The Anglo-Spanish War is fought on both sides of the Atlantic.
- The reign of Abbas I marks the zenith of the Safavid dynasty.
- England repulses the Spanish Armada.
- Spain repulses the English Armada.
- Gazi Giray leads a huge Tatar expedition against Moscow.
- In Mali, Moroccan forces of the Sultan Ahmad al-Mansur led by Judar Pasha defeat the Songhai Empire at the Battle of Tondibi.
- John Stow reports 10,675 plague deaths in London, a city of approximately 200,000 people by the end of 1593.
- Korea, with the help of Ming Dynasty China, repels two Japanese invasions until 1598.
- The Long War between the Habsburg monarchy and the Ottoman Turks begins.
- The Edict of Nantes ends the French Wars of Religion.
- Abbas I moved Safavids capital from Qazvin to Isfahan in 1598.
- Russia descends into anarchy during the Time of Troubles.
- The Mali Empire is defeated at the Battle of Jenné
- Giordano Bruno is burned at the stake for heresy in Rome.
- Battle of Sekigahara in Japan. End of the Warring States period and beginning of the Edo period.