January 19 – King Christian II of Denmark and Norway defeats the Swedes at Lake Åsunden in Sweden. The Swedish regent Sten Sture the Younger is mortally wounded in the battle. He is rushed towards Stockholm, in order to lead the fight against the Danes from there, but dies from his wounds on February 3.
April 16 – Revolt of the Comuneros: Citizens of Toledo, Castile opposed to the rule of the Flemish-born Charles V, Holy Roman Emperor, rise up when the royal government attempts to unseat radical city councilors.
June – Moctezuma II, Aztec ruler of Tenochtitlan, is declared deposed due to his captivity by conquistador Hernán Cortés. His brother Cuitláhuac rises to the throne.
June 7 – King Henry VIII of England and King Francis I of France meet at the famous Field of Cloth of Gold.
June 10 – Revolt of the Comuneros: Blockade of Segovia.
June 15 – Pope Leo X issues the bull Exsurge Domine (Arise O Lord), threatening Martin Luther with excommunication if he does not recant his position on indulgences and other Catholic doctrines.
July 1 – La Noche Triste (Night of Sorrow): The forces of Cuitláhuac, Aztec ruler of Tenochtitlan, gain a major victory against the forces of conquistador Hernán Cortés. This results in the death of about 400 conquistadors and some 2,000 of their Native American allies. However, Cortés and the most skilled of his men manage to escape and later regroup.
July 20 – The Spaniards defeat the Aztecs at Otumba near Lake Texcaco.
August – Martin Luther writes To the Christian Nobility of the German Nation.
September 7 – Christian II makes his triumphant entry into Stockholm, which has surrendered to him a few days earlier. Sten Sture's widow Christina Gyllenstierna, who has led the fight after Sten's death, and all other persons in the resistance against the Danes, are granted amnesty and are pardoned for their involvement in the resistance.
September 22 – Suleiman I succeeds his father Selim I as Sultan of the Ottoman Empire.
October – Cuitláhuac, Aztec ruler of Tenochtitlan, dies from smallpox. He is succeeded by his nephew Cuauhtémoc.
October 21 (Feast of St. Urusula) – The islands of Saint Pierre and Miquelon are discovered by Portuguese explorer João Álvares Fagundes off Newfoundland. He names them "Islands of the 11,000 Virgins" in honour of Saint Ursula.
November 1 – Christian II is elected king of Sweden.
November 4 – Christian II is crowned king of Sweden. The coronation is followed by a three-day feast in Stockholm.
November 7 – At the end of the third day of Christian's coronation feast, several leading figures of the Swedish resistance against the Danish invasion are imprisoned and tried for high treason.
November 8–November 10 – 82 noblemen and clergymen, having been sentenced to death for their involvement in the Swedish resistance against the Danish invasion, are executed by beheading in the Stockholm Bloodbath.
November 28 – After navigating through the South American strait, three ships under the command of Portuguese explorer Ferdinand Magellan reach the Pacific Ocean, becoming the first Europeans to sail from the Atlantic Ocean to the Pacific (the strait was later named the Strait of Magellan).
December 10 – Martin Luther burns a copy of The Book of Canon Law (see Canon Law) and his copy of the Papal bull Exsurge Domine.
The Franciscan friar Matteo Bassi is inspired to return to the primitive life of solitude and penance as practiced by St. Francis, giving rise to the Order of Friars Minor Capuchin.
Duarte Barbosa returns to Cananor.
Aleksandra Lisowska (Roxelana) is given as a gift to Suleiman I on the occasion of his accession to the throne.
January 3 – Pope Leo X excommunicates Martin Luther in the papal bull Decet Romanum Pontificem.
January 22 – Charles V, Holy Roman Emperor, opens the Diet of Worms in Worms, Germany.
January 27 – Suleiman the Magnificent suppresses a revolt by the ruler of Damascus.
January 28 – The Diet of Worms begins, lasting until May 25.
February 2 – The Nydala Abbey Bloodbath take place in Nydala Abbey in Sweden.
Ferdinand Magellan discovers Guam.
Martin Luther is summoned to appear before the Diet of Worms.
March 16 – Ferdinand Magellan reaches the Philippines. Starting this year, the Philippines is now one day behind its Asian neighbors.
Ferdinand Magellan arrives at Cebu.
Martin Luther preaches an inflammatory sermon to students at Erfurt while on his way to Worms.
April 16–18 – Martin Luther is examined before Emperor Charles V and the Diet of Worms.
April 24 – Revolt of the Comuneros – Battle of Villalar: Castilian royalists defeat the rebels and execute their three leaders.
April 26 – Martin Luther leaves Worms and disappears for a year – he is rumored to be murdered, but is actually in hiding at the Wartburg castle.
April 27 – Ferdinand Magellan is killed in the Philippines, in the Battle of Mactan.
May – Italian War of 1521–26 breaks out between Charles V, Holy Roman Emperor, and Francis I of France.
May 17 – Edward Stafford, 3rd Duke of Buckingham, is executed for treason in London.
May 20 – Battle of Pampeluna: The French defeat the Spanish.
May 25 – The Diet of Worms ends when Charles V, Holy Roman Emperor issues the Edict of Worms, declaring Martin Luther an outlaw.
May 27 – Jiajing Emperor ascends the throne of the Ming dynasty.
June 29 or 30 – The oldest surviving dateable document written primarily in the Romanian language: Neacșu's letter, written by a trader from Câmpulung, to Johannes Benkner, the mayor of Brașov, warning that the Ottoman Empire is preparing its troops to cross into Wallachia and Transylvania; the script used is Romanian Cyrillic.
June 30 – Battle of Esquiroz: French forces under Henri d'Albret, exiled King of Navarre, are defeated by the Spanish and forced to abandon their attempt to recover Henri's kingdom.
July – Pfaffensturm: Student rebellion against priests in Erfurt.
August 8 – Fall of Tenochtitlan: Hernán Cortés and allied local indigenous peoples of the Americas defeat the Aztec forces of Cuauhtémoc, the last Tlatoani (Aztec Emperor), at Tenochtitlan in the Valley of Mexico.
August 13 – Fall of Tenochtitlan: Cuauhtémoc surrenders to Cortés, thus incorporating the Aztec Empire into the Spanish Empire.
August 23 – Christian II of Denmark is deposed as king of Sweden and Gustav Vasa is elected new Swedish regent.
August 29 – Belgrade is captured by the Ottoman army of Suleiman the Magnificent.
November 23 – Spanish–German–Papal forces under Prospero Colonna force French Marshal Odet de Lautrec to abandon Milan.
Jacopo Berengario da Carpi publishes Commentaria cum amplissimus additionibus super anatomiam Mundini in Bologna, including observation of the vermiform appendix.
San Juan Bautista is founded in the archipelago of Puerto Rico.
The principality of Ryazan is annexed by the Grand Duchy of Moscow.
January 9 – Pope Adrian VI (born Adriaan Florenszoon Boeyens, Dedens or Dedel; Hadrianus in Latin) succeeds Pope Leo X as the 218th pope. The only Dutch pope, he will be the last non-Italian elected for more than 450 years.
April 27 – 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.
May – England presents an ultimatum to France and Scotland.
June 19 – Charles V, Holy Roman Emperor visits King Henry VIII of England and signs the Treaty of Windsor pledging a joint invasion of France, bringing England into the Italian War of 1521–1526.
July – The English army attacks Brittany and Picardy from Calais, burning and looting the countryside.
July 28 – Ottoman Sultan Suleiman I begins his 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 Sanlúcar de Barrameda in Spain under the command of Juan Sebastián Elcano, becoming the first ship to circumnavigate the world.
September – Luther Bible: Martin Luther's translation of the Bible's New Testament into Early New High German from Greek, Das newe Testament Deutzsch, is published in Germany, selling thousands in the first few weeks.
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.
The Diet of Nuremberg is held.
The Knights' Revolt erupts in Germany.
Costa Rica is named by the Spanish colonizer Gil González Dávila when he finds copious quantities of gold in Pacific beaches.
The third edition of Erasmus's Greek Textus Receptus of the Bible is published.
Chinese Ming Dynasty records indicate that the War Ministry official He Ru is the first to acquire the Portuguese breech-loading culverin, while copies of them are made by two Westernized Chinese at Beijing, Yang San (Pedro Yang) and Dai Ming.
Some believe that Australia is sighted by a Portuguese expedition led by Cristóvão de Mendonça who maps the continent and names it Jave la Grande ("The Greater Java").
April – Martin Luther helps Katharina von Bora, his eventual wife, escape from the Nimbschen convent by placing her and 12 other nuns in herring barrels.
May – The Ningbo Incident: Two rival trade delegations from Japan feud in the Chinese city of Ningbo, resulting in the pillage and plunder of the city.
June 6 – Gustav Vasa is elected king of Sweden, finally establishing its full independence of Sweden from Denmark, marking the end of the Kalmar Union.
July 1 – Johann Esch and Heinrich Voes became the first Flemish Lutheran martyrs, burned at the stake by Roman Catholic authorities in Brussels.
November 19 – Pope Clement VII succeeds Pope Adrian VI as the 219th pope.
The Ming Dynasty Chinese navy captures two Western ships with Portuguese breech–loading culverins aboard, which the Chinese call a fo–lang–ji (Frankish culverin). According to the Ming Shi, these cannons are soon presented to the Jiajing Emperor by Wang Hong, and their design is copied in 1529.
Martin Luther's translation of the Pentateuch into German (Das allte Testament Deutsch) is published.
Wijerd Jelckama, a Frisian warlord and military commander is executed in Leeuwarden. His death ends the successful Frisian rebellion fought by the Arumer Black Heap.
The Swabian League destroyed 23 robber baron castles in the Franconian War.
January 17 – Florentine explorer Giovanni da Verrazzano, on board La Dauphine in the service of Francis I of France, sets out from Madeira for the New World to seek out a westabout sea route to the Pacific Ocean.
March – Spanish conquistador Pedro de Alvarado destroys the K'iche' kingdom of Q'umarkaj, taking the capital, Quiché.
March 1 (approximate date) – da Verrazzano's expedition makes landfall at Cape Fear.
April 17 – Verrazzano's expedition makes the first European entry into New York Bay and sights the island of Manhattan.
April 30 – Spanish forces under Charles de Lannoy defeat the French army in Italy under William de Bonnivet in the Battle of the Sesia. The French, now commanded by François de St. Pol, withdraw from the Italian Peninsula.
June 8 – Spanish conquistador Pedro de Alvarado leads the Battle of Acajutla, defeating a battalion of Pipiles, in the neighborhoods of present day Acajutla, El Salvador
Summer – Paracelsus visits Salzburg. He also visits Villach during the year.
July 8 – Verrazzano's expedition returns to Dieppe.
August–September – Marseille is besieged by Imperial forces under the Duke of Bourbon.
Late August – Protestant theologians Martin Luther and Andreas Karlstadt dispute at Jena.
October 28 – A French army invading Italy under King Francis besieges Pavia.
December 8 – Francisco Hernandez de Cordoba founds the city of Granada, Nicaragua, the oldest Hispanic city in the mainland of the Western Hemisphere.
The first Dalecarlian rebellions in Sweden.
January 21 – The Swiss Anabaptist Movement is born when Conrad Grebel, Felix Manz, George Blaurock, and about a dozen others baptize each other in the home of Manz's mother on Neustadt-Gasse, Zürich, breaking a thousand-year tradition of church-state union.
February 24 – Battle of Pavia: Spanish forces under Charles de Lannoy and the Marquis of Pescara defeat the French army and capture Francis I of France, after his horse is wounded by Cesare Hercolani.
February 28 – The last Aztec Emperor, Cuauhtémoc, is killed by Hernán Cortés.
March 20 – In the German town Memmingen the pamphlet The Twelve Articles: The Just and Fundamental Articles of All the Peasantry and Tenants of Spiritual and Temporal Powers by Whom They Think Themselves Oppressed is published , the first human rights related document written in Europe.
April 10 – Albert, Duke of Prussia commits Prussian Homage.
May 15 – Insurgent peasants led by radical pastor Thomas Müntzer were defeated at the Battle of Frankenhausen, ending the German Peasants' War in the Holy Roman Empire.
June 13 – Martin Luther marries ex-nun Katharina von Bora. The painter Lucas Cranach the Elder is one of the witnesses.
June 16 – Henry VIII of England appoints his illegitimate son Henry FitzRoy Duke of Richmond and Somerset.
July 29 – Santa Marta, the first city in Colombia, is founded by Spanish conqueror Rodrigo de Bastidas.
European-brought diseases sweep through the Andes, killing thousands, including the Inca.
Mixco Viejo, capital of the Pocomam Maya State, falls to the Spanish Conquistadores of Pedro de Alvarado in what is now Guatemala after a 3-month siege.
The Bubonic plague spreads in southern France.
The New Testament is translated into English by William Tyndale.
The first French ambassador arrives in Istanbul.
The start of the Navarre witch trials (1525-26).
The Chinese Ministry of War under the Ming dynasty orders ships having more than one mast sailing along the southeast coast to be seized, investigated, and destroyed; this in an effort to curb piracy and limit private commercial trade abroad.
Over 75,000 peasants are killed in Germany.
Francis I of France and Suleiman I strike an alliance against Habsburg Empire.
Age of Samael ends and the Age of Gabriel starts according to Johannes Trithemius.
January 14 – Treaty of Madrid: Peace is declared between Francis I of France and Charles V, Holy Roman Emperor. Francis agrees to cede Burgundy to Charles, and abandons all claims to Flanders, Artois, Naples, and Milan.
April 21 – Battle of Panipat: Babur becomes Mughal emperor, invades northern India and captures Delhi, beginning the Mughal Empire, which lasts until 1857.
May 22 – Francis repudiates the Treaty of Madrid and forms the League of Cognac against Charles, including Pope Clement VII, Milan, Venice, and Florence.
May 24 – A Transit of Venus occurs, the last before optical filters allowed astronomers to observe them.
June 9 – Emperor Go-Nara ascends to the throne of Japan.
July – The Spanish ship Santiago from García Jofre de Loaísa's expedition reaches the Pacific Coast of Mexico, the first to navigate from Europe to the west coast of North America.
July 24 – Milan is captured by the Spanish.
August 21 – Spanish explorer Alonso de Salazar becomes the first European to sight the Marshall Islands in the Pacific Ocean.
August 29 – Battle of Mohács: The Turkish army of Sultan Suleiman I defeats the Hungarian army of King Louis II, who is killed in the retreat. Suleiman takes Buda, while Archduke Ferdinand of Austria and John Zápolya, Prince of Transylvania, dispute the succession. As a result of the battle, Dubrovnik achieves independence, although it acknowledges Turkish overlordship.
December – Paracelsus arrives at Strasbourg.
Spring – The first complete printed translation of the New Testament of the Bible into the English language by William Tyndale arrives in England from Germany, having been printed in Worms. In October, Cuthbert Tunstall, Bishop of London, attempts to collect all the copies in his diocese and burn them.
The first official translation is made of the New Testament into Swedish, the entire Bible is completed in 1541.
Gunsmith Bartolomeo Beretta establishes the Beretta Gun Company, which will still be in business in the 21st century, making it one of the world's oldest corporations.
January 5 – Felix Manz, co-founder of the Swiss Anabaptists, is drowned in the Limmat in Zürich by the Zürich Reformed state church.
March 17 – Battle of Khanwa: This and two other major Moghul victories lead to their domination of northern India.
March – Paracelsus is appointed as town physician of Basle.
April 30 – Treaty of Westminster (1527), an alliance during the War of the League of Cognac.
May 6 – Sack of Rome: Spanish and German troops led by the Duke of Bourbon sack Rome, forcing Pope Clement VII to make peace with Charles V, Holy Roman Emperor, marking the end of the High Renaissance. The Pope grows a beard in mourning.
May 16 – In Florence, the Piagnon, a group devoted to the memory of Girolamo Savonarola, drive out the Medici for a second time, re-establishing the Republic of Florence until 1530.
June 17 – The Narváez expedition to conquer Florida sets sail from Spain.
June 17 – The Protestant Reformation begins in Sweden. The Riksdag of the Estates in Västerås adopts Lutheranism as the state religion in place of Roman Catholicism.
June 21 – Niccolò Machiavelli, Italian historian, politician, diplomat, philosopher and humanist dies in Florence, Italy.
June 22 – Jakarta, current capital of Indonesia, was founded as Jayakarta.
June 23 – Paracelsus burns books of Avicenna.
August 3 – The first known letter is sent from North America by John Rut while at St. John's, Newfoundland.
August 20 – Sixty Anabaptists meet at the Martyrs' Synod in Augsburg.
August 20 – Diet of Odense (Denmark). King Frederick I declares religious tolerance for Lutherans, permits marriage of priests and forbids seeking papal pallium (approval) for royal appointments of Church officials.
September 27 – Battle of Tarcal: Ferdinand, future Holy Roman Emperor, defeats John Zápolya and takes over most of Hungary. John appeals to the Turks for help.
The Spanish conquest of Guatemala highlands is completed; the first Guatemala City (Ciudad Vieja) is founded.
Spanish Conquistador Francisco de Montejo invades Yucatán.
Members of the University of Wittenberg flee to Jena in fear of the bubonic plague.
Bishop Vesey's Grammar School at Sutton Coldfield in the West Midlands of England is founded by Bishop John Vesey.
Sir George Monoux College is founded as a grammar school at Walthamstow, England, by Sir George Monoux, draper and Lord Mayor of London.
The Ming Dynasty government of China greatly reduces the quotas for taking grain, severely diminishing the state's capacity to relieve famines through a previously successful granary system.
The second Dalecarlian rebellions in Sweden.
January 12 – Gustav I of Sweden is crowned king of Sweden, having already reigned since his election in June 1523.
Peasant uprising in Dalarna, Sweden: rebel campaign fails and the rebel leader, later known as Daljunkern, flees to Rostock.
Diego García de Moguer explores the Sierra de la Plata along the Río de la Plata and begins to travel up the Paraná River.
Paracelsus visits Colmar in Alsace.
June 19 – Battle of Landriano: A French army in Italy under Marshal Francis de Bourbon, Count of St. Pol is decisively defeated.
September 12 – Andrea Doria defeats his former allies, the French, and establishes the independence of Genoa.
October 3 – Álvaro de Saavedra Cerón arrives in the Maluku Islands.
October 13 – Cardinal Thomas Wolsey founds a college in his birthplace of Ipswich in England, which becomes the modern-day Ipswich School (incorporating institutions in the town dating back to 1299).
October 20 – The Treaty of Gorinchem is signed between Charles V, Holy Roman Emperor, and Charles, Duke of Guelders.
November 6 – Spanish conquistador Álvar Núñez Cabeza de Vaca and his companions become the first known Europeans to set foot on the shores of what is present-day Texas.
Montenegro gains autonomy under Turkish power.
The Maya peoples drive Spanish Conquistadores out of Yucatán.
Spain takes direct control of Acapulco.
Bubonic plague breaks out in England.
The fourth major outbreak of the sweating sickness occurs in England. This time the disease also spreads to northern Europe.
St George's Chapel in Windsor Castle is completed.
Chateau Fontainebleau in France is begun.
Michelangelo Buonarroti begins work on the fortifications of Florence.
Baldassare Castiglione publishes The Book of the Courtier.
In Henan province of China, during the mid Ming Dynasty, a vast drought deprives the region of harvests for the next two years, killing off half the people in some communities due to starvation and cannibalism.
Paracelsus leaves Basle.
March 7–March 9 – Battle of Shimbra Kure: Imam Ahmad ibn Ibrahim al-Ghazi, with 200 men armed with matchlocks, defeats the army of Lebna Dengel, Emperor of Ethiopia.
April 8 – Flensburg Disputation, a debate, attended by Stadtholder Christian of Schleswig-Holstein (later King Christian III of Denmark) between Lutherans (led by Hermann Fast) and the more radical Anabaptists (led by Melchior Hoffman). Johannes Bugenhagen, a close associate of Martin Luther, presides. The Disputation marks the rejection of radical ideas by the Danish Reformation.
April 9 – The Westrogothian rebellion in Sweden.
April 19 – At the Diet of Speyer, a group of rulers (German: Fürst) and independent cities (German: Reichsstadt) protest the reinstatement of the Edict of Worms, beginning the Protestant movement.
April 22 – The Treaty of Zaragoza divides the eastern hemisphere between Spanish and Portuguese empires, stipulating that the dividing line should lie 297.5 leagues or 17° east of the Moluccas.
May–July – Cardinal Thomas Wolsey, Archbishop of York, presides over a legatine court at Blackfriars, London, to rule on the legality of King Henry VIII of England's marriage to Catherine of Aragon.
May 10 – The Turkish army under Suleiman I leaves Constantinople to invade Hungary once again.
June 21 – War of the League of Cognac: Battle of Landriano: French forces in northern Italy are decisively defeated by Spain.
July 30 – The only Continental outbreak of English sweating sickness reaches Lübeck, spreading from there into Schleswig-Holstein in the next few months.
August 5 – Charles V, Holy Roman Emperor, and Francis I of France sign the Treaty of Cambrai, or "Ladies' Peace" in the War of the League of Cognac: Francis abandons his claims in Italy, but is allowed to retain the Duchy of Burgundy. Henry VIII of England accedes on August 27.
September 1 – Sancti Spiritu, the first European settlement in Argentina, is destroyed by local natives.
Buda is recaptured by the invading forces of the Ottoman Empire.
The city of Maracaibo, Venezuela is founded by Ambrosius Ehinger.
September 23 – Siege of Vienna: Vienna is besieged by the Ottoman forces of Suleiman the Magnificent.
October 15 – With the season growing late, Suleiman abandons the Siege of Vienna, a turning point in the Ottoman wars in Europe.
October 26 – Cardinal Wolsey falls from power in England due to his failure to prevent Habsburg expansion in Europe and obtain an annulment of Henry VIII's marriage. Thomas More succeeds him as Lord Chancellor.
November 4–December 17 – First sitting of the English Reformation Parliament.
Aylesbury is granted the county town of Buckinghamshire in England by King Henry VIII.
Stephen Báthory becomes governor of Transylvania.
Boromrajathira IV succeeds Rama Thibodi II as king of Ayutthaya.
Fluorite is first described by Georg Agricola.
Giorgio Vasari visits Rome.
Pietro Bembo becomes historiographer of Venice.
Heinrich Bullinger becomes pastor of Bremgarten, Switzerland.
Paracelsus visits Nuremberg.
Paracelsus uses the name Paracelsus for the first time.
Occultist Heinrich Cornelius Agrippa publishes Declamatio de nobilitate et praecellentia foeminei sexus ("Declamation on the Nobility and Preeminence of the Female Sex"), a book pronouncing the theological and moral superiority of women.
25 March — Blood libel against the Jewish community of Bosen (formerly in Hungary, today in Slovakia), on the first day of Passover. Three Jews are accused and killed, while the boy is discovered alive, kidnapped for the benefit of the scheme.