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1530s decade ran from January 1, 1530, to December 31, 1539.
July 25 – The city of Santiago de Querétaro, Mexico is founded.
August 26 – Comet Halley achieves its perihelion.
September 22 – Battle of Obertyn: The Moldavians are defeated by Polish forces under Jan Tarnowski, allowing the Poles to recapture Pokucie.
October 11 – Battle of Kappel: The forces of Zürich are defeated by the Catholic cantons. Huldrych Zwingli, the Swiss religious reformer, is killed.
October 28 – Battle of Amba Sel: Imam Ahmad ibn Ibrahim al-Ghazi again defeats the army of Lebna Dengel, Emperor of Ethiopia. The southern part of Ethiopia thus falls under Imam Ahmad's control.
December 9 - The Virgin of Guadalupe first appears to Juan Diego at Tepeyac, Mexico City.
December 12 – Mary, mother of Jesus, in the guise of Our Lady of Guadalupe, appears imprinted on the tilmàtli of Juan Diego Cuauhtlatoatzin, an Aztec convert to Catholicism, in Tepeyac near Mexico City.
July 11 – Henry VIII is excommunicated by Pope Clement VII, as is Archbishop Cranmer.
July 22 – Treaty of Constantinople between the Ottoman Empire and the Archduchy of Austria: Ferdinand I, King of the Romans, withdraws his claims to most of Hungary and János Szapolyai, voivode of Transylvania, becomes King of Hungary under the suzerainty of Suleiman the Magnificent, Sultan of the Ottoman Empire.
July 26 – Sapa Inca Atahualpa is executed by garotte, at the orders of Francisco Pizarro in Cajamarca. The Spanish arrange for his younger brother Túpac Huallpa to be crowned as a successor, but he dies of smallpox soon afterwards.
September 7 – Anne Boleyn gives birth to Princess Elizabeth, the future Elizabeth I of England.
November 15 – Francisco Pizarro arrives in Cusco, Peru.
December 3 – Ivan IV succeeds his father Vasili III as Grand Prince of Muscovy at the age of three years.
December – Hernando de Grijalva and his crew discover the uninhabited Revillagigedo Islands, off the Pacific coast of Mexico.
January 15 – The Parliament of England passes the , recognising the marriage of Act Respecting the Oath to the Succession Henry VIII and Anne Boleyn, and their children as the legitimate heirs to the throne. 
February 23 – A group of Anabaptists, led by Jan Matthys, seize Münster, Westphalia and declare it The New Jerusalem, begin to exile dissenters, and forcibly baptize all others.
April 5 ( Easter Sunday) – Anabaptist Jan Matthys is killed by the Landsknechte, who lay siege to Münster on the day he predicted as The Second Coming of Christ. His follower John of Leiden takes control of the city.
April 7 – Sir Thomas More is confined in the Tower of London.
May 10 – Jacques Cartier explores Newfoundland, while searching for the Northwest Passage.
June 9 – Jacques Cartier is the first European to discover the Saint Lawrence River.
June 23 – Copenhagen opens its gates to Count Christopher of Oldenburg, leading the army of Lübeck (and the Hanseatic League), nominally in the interests of the deposed King Christian II of Denmark. The surrenders of Copenhagen and, a few days later, of Malmö represent the high point of the Count's War for the forces of the League. These victories presumably lead the Danish nobility to recognize Christian III as King on July 4.  
June 29 – Jacques Cartier discovers Prince Edward Island.
July 4 – The Election of Christian III, as King of Denmark and Norway, takes place in the town of Rye.
July 7 – The first known exchange occurs between Europeans and natives of the Gulf of St. Lawrence, in New Brunswick.
August 15 – Ignatius of Loyola and six others take the vows that lead to the establishment of the Society of Jesus, in Montmartre (Paris).
August 26 – Piero de Ponte becomes the 45th Grandmaster of the Knights Hospitaller.
October 13 – Pope Paul III succeeds Pope Clement VII, as the 220th pope.
October 18 – Huguenots post placards all over France attacking the Catholic Mass, provoking a violent sectarian reaction.
November 3– December 18 – The English Reformation Parliament passes the Act of Supremacy, establishing Henry VIII as supreme head of the Church of England. 
December 6 – Over 200 Spanish settlers, led by conquistador Sebastián de Belalcázar, found what is now Quito, Ecuador.
Act for the
Submission of the Clergy is confirmed by the Parliament of England, requiring churchmen to submit to the king, and forbidding the publication of ecclesiastical laws without royal permission.
Manco Inca Yupanqui is crowned as Sapa Inca in Cusco, Peru by Spanish conquistador Francisco Pizarro, in succession to his brother Túpac Huallpa (d. October 1533).
Cambridge University Press is given a Royal Charter by Henry VIII of England, and becomes the first of the privileged presses.
is published by Gargantua François Rabelais.
Martin Luther's translation of the complete Christian Bible into German is printed by Hans Lufft in Wittenberg, adding the Old Testament and Apocrypha to Luther's 1522 translation of the New Testament, and including woodcut illustrations. The first book in
Yiddish is printed (in Kraków), Mirkevet ha-Mishneh, a Tanakh concordance by Rabbi Asher Anchel, translating difficult phrases in biblical Hebrew. 
January 18 – Lima, Peru, is founded by Francisco Pizarro, as . Ciudad de los Reyes
February 27 – George Joye publishes his Apologye in Antwerp, to clear his name from the accusations of William Tyndale.
March – English forces under William Skeffington storm Maynooth Castle in Ireland, the stronghold of Thomas FitzGerald, 10th Earl of Kildare. 
March 10 – Fray Tomás de Berlanga discovers the Galápagos Islands, when blown off course en route to Peru.
May 4 – The first of the English Carthusian Martyrs is executed.
May 10 – Amsterdam: A small troop of Anabaptists, led by the minister Jacob van Geel, attacks the city hall, in an attempted coup to seize the city. In the counter-attack by the city's militia, the burgemeester, Pieter Colijns, is killed by the rebels. In another incident this year in Amsterdam, seven men and five woman walk nude in the streets; and Anabaptists rebel in other cities of the Netherlands. 
May 19 – French explorer Jacques Cartier sets sail for his second voyage to North America with three ships, 110 men, and Chief Donnacona's two sons (taken by Cartier during his first voyage).
May 20 – William Tyndale is arrested in Antwerp for heresy, in relation to his Bible translation, and imprisoned in  Vilvoorde.
June 1 – The Conquest of Tunis by Charles V, Holy Roman Emperor, begins with the destruction of Barbarossa's fleet. Following the eventual capture of the city from the Ottoman Empire, around 30,000 inhabitants are massacred.
June 8 – Battle of Bornholm: Combined Swedish and Danish fleets defeat the Hanseatic navy.
June 22 – Cardinal John Fisher, Bishop of Rochester, is executed for his refusal to swear an oath of loyalty to King Henry VIII of England. 
June 24 – Münster Rebellion: The Anabaptist state of Münster is conquered and disbanded.
July 6 – Sir Thomas More, author of and one time Utopia Lord Chancellor of England, is executed for treason, after refusing to recognize King Henry VIII as head of the English Church, and separate from the Roman Catholic Church. 
July 15 – Archdeacon Charles Reynolds (cleric), envoy to James V, Charles V, and Pope Paul III, is buried in Rome. He died of malaria while lobbying for the excommunication of King Henry VIII for heresy.
October 2 – Jacques Cartier reaches the island in the Saint Lawrence River, that eventually becomes Montreal.
October 4 – The first complete English-language Bible is printed in Antwerp, with translations by William Tyndale and Myles Coverdale.
December – Manco Inca Yupanqui, nominally Sapa Inca, is imprisoned by the Spanish Conquistadors of Peru.
January 7 – Catherine of Aragon, first queen of Henry VIII of England, dies.
January 22 – John of Leiden, Bernhard Knipperdolling, and Bernhard Krechting are executed in Münster for their roles in the Münster Rebellion.
February 2 – Spaniard Pedro de Mendoza founds Buenos Aires, Argentina.
February 25 – Jacob Hutter is burned at the stake for heresy.
April 30 – The Inquisition is implemented in Portugal.
May 2 – Anne Boleyn, second queen of Henry VIII of England, is arrested on the grounds of incest, adultery, and treason.
May 6 – Incan emperor Manco Inca Yupanqui, having on April 18 escaped from imprisonment in Cuzco, begins his revolt against his captors, when his army begins the 10-month Siege of Cuzco, against a garrison of Spanish conquistadors and Indian auxiliaries, led by Hernando Pizarro.
May 17 – The five men accused of adultery with Anne Boleyn, including her own brother George Boleyn, are executed.
May 19 – Anne Boleyn, queen consort of Henry VIII of England is executed in the Tower of London.
May 30 – Henry VIII of England marries Jane Seymour.
June 24 – Cristóbal de Oñate founds San Juan Bautista del Teul.
June 26 – Andrés de Urdaneta and a few companions arrive in Lisbon, completing a circumnavigation which began with de Loaísa's expedition of 1525.
June 27 – San Pedro Sula is founded by Pedro de Alvarado.
War resumes between Francis I of France and Charles V, Holy Roman Emperor. Francis seizes control of Savoy, and captures Turin. Charles triumphally enters Rome, following the Via Triumphalis, and delivers a speech before the Pope and College of Cardinals, publicly challenging the king of France to a duel.
Battle of Un no Kuchi: Takeda Family forces defeat Hiraga Genshin. Various religious buildings are closed as part of
Henry VIII of England's Dissolution of the Monasteries, including
The legal and political union of
Wales with England is reinforced, by . An Acte for Lawes & Justice to be ministred in Wales in like fourme as it is in this Realme
Reformation in Denmark–Norway and Holstein: Protestantism is introduced in Denmark and Norway, by King Christian III.
John Calvin's , a seminal work of Institutio Christianæ religionis Protestant systematic theology, is published. 
Battle of Reynogüelén: Spanish conquistadors defeat the Mapuches in Chile, in the opening battle of the Arauco War. The
Portuguese crown divides Colonial Brazil into fifteen donatory captaincies. A
trade compact exempts French merchants from Ottoman law and allows them to travel, buy and sell throughout the sultan's dominions, and to pay low customs duties on French imports and exports. The compact is renewed in 1569.
January – Bigod's Rebellion, an uprising by Roman Catholics against Henry VIII of England, is crushed.
January 6 – Alessandro de' Medici, Duke of Florence, is assassinated.
March – Diego de Almagro successfully charges Manco Inca's siege of Cuzco, thereby saving his antagonists, the Pizarro brothers.
March 12 – Recife is founded by the Portuguese, in Brazil.
April 1 – Catholicism is definitively ended in Norway. Archbishop Olav Engelbrektsson flees from Nidaros ( Trondheim) to Lier, Belgium.
June 2 – Pope Paul III publishes the encyclical , which declares the natives of the Sublimis Deus New World to be rational beings with souls, who must not be enslaved or robbed.
Henan province, China, a severe drought with swarms of locusts is made worse, by a major epidemic outbreak of the plague. The first printing press in
North America is set up in Mexico City.  Teseo Ambrogio's
Introductio in Chaldaicam lingua, Syriaca atq Armenica, & dece alias linguas, published in Pavia, introduces several Middle Eastern languages to western Europe for the first time.
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