The 1500s ran from January 1, 1500, to December 31, 1509.
- January 5 – Duke Ludovico Sforza recaptures Milan, but is soon driven out again by the French.
- January 26 – Spanish navigator Vicente Yáñez Pinzón reaches the northern coast of Brazil.
- February 17 – Battle of Hemmingstedt: The Danish army fails to conquer the peasants' republic of Dithmarschen.
- April 22 – Portuguese navigator Pedro Álvares Cabral officially discovers Brazil, and claims the land for the Kingdom of Portugal. He has 13 vessels with him.
- July 14 – The Muscovites defeat the Lithuanians and the Poles in the Battle of Vedrosha.
- August – : The Turkish fleet of Kemal Reis defeats the Venetians in the Second Battle of Lepanto. The Turks proceed to capture Modon and Coron, the "two eyes of the Republic".
- August 10 – Diogo Dias discovers an island which he names St Lawrence (after the saint's day on which it was first sighted), later to be known as Madagascar.
- November 11 – Treaty of Granada: Louis XII of France and Ferdinand II of Aragon agree to divide the Kingdom of Naples between them.
- November 16 – Emperor Go-Kashiwabara accedes to the throne of Meiō era Japan.
- December 24 – The Siege of the Castle of St. George ends, and the island of Cephalonia is captured by a joint Venetian–Spanish fleet.
- December 31 – The last of the incunabula are published.
- Europe's population is estimated at 56.7 million people (Spielvogel).
- Heinrich Cornelius Agrippa is admitted to baccalaureate.
- Saxony's mint at Annaberg begins producing guldengroschens.
- Although other reports exist, it is thought that the last wolf in England was killed this year, making the species extinct in that country. The wolf is thought to have been killed in Allithwaite, in Cumbria. However, reports of wolf sightings and laws concerning wolf bounties existed in rural areas of the north until the 18th century.
- January 17 – Cesare Borgia returns triumphantly to Rome, from Romagna.
- March 25 – Portuguese navigator João da Nova probably discovers Ascension Island. It is definitely sighted and named on May 20, 1503 (Feast of the Ascension) by Afonso de Albuquerque.
- April – The Rebellion of the Alpujarras ends with the surrender of the last Muslim insurgents in the Alpujarra Mountains, who are given the choice of expulsion or conversion to Christianity.
- May 15 – Harmonice Musices Odhecaton, the first printed collection of polyphonic music, is published by Ottaviano Petrucci in Venice.
- July – Ismail I is enthroned as Shah of Azerbaijan, choosing Tabriz as his capital, founding the Safavid Dynasty in northern Iran. He declares Shi'ism the official and compulsory religion, under penalty of death.
- July 21 – Portuguese explorer Pedro Cabral returns to Lisbon, from his expedition to Calicut (Nicolau Coelho having arrived on June 23).
- July 27 – Copernicus is formally installed, as canon of Frauenberg Cathedral.
- August 27 – Battle of the Siritsa River: The Livonian Order, supporting the Grand Duchy of Lithuania in the Second Muscovite–Lithuanian War, and commanded by Wolter von Plettenberg, defeats an army of the Grand Duchy of Moscow and Pskov Republic.
- October 13 – Treaty of Trente: Maximilian of Austria and Louis XII of France sign the treaty, with Austria recognizing all French conquests in the northern territories of Italy.
- October 30 – The Banquet of Chestnuts is purportedly held by Cesare Borgia, in the Papal Palace of Rome (this account is not historical fact, and could be attributed to enemies of Alexander VI).
- November 1 (All Saints) – Amerigo Vespucci discovers and names Baía de Todos os Santos, in Brazil.
- November 4
- November 12 – Sten Sture the Elder is elected Regent of Sweden for the second time.
- November 14 – Arthur, Prince of Wales, marries the Spanish princess Catherine of Aragon.
- November 24 – A large army of the Grand Duchy of Moscow overruns Livonia during the Second Muscovite–Lithuanian War.
- December 12 – Alexander Jagiellon becomes King of Poland.
- The Swiss cantons of Basel and Schaffhausen join the Old Swiss Confederacy.
- Gaspar Corte-Real, Portuguese navigator, makes the first documented European landing in North America since c. 1000 A.D.
- Rodrigo de Bastidas, sailing westward from Venezuela in search of gold, becomes the first European to explore the Isthmus of Panama.
- Amerigo Vespucci maps the two stars Alpha Centauri and Beta Centauri, as well as the stars of the constellation Crux, which are below the horizon in Europe.
- Michelangelo returns to his native Florence, to begin work on the statue David.
- Italic type (cut by Francesco Griffo) is first used by Aldus Manutius at the Aldine Press in Venice, in an edition of Virgil.
- Martin Luther enters the University of Erfurt.
- January 1 – Portuguese explorers, led by Gonçalo Coelho, sail into Guanabara Bay, Brazil, mistaking it for the mouth of a river, which they name Rio de Janeiro.
- February 12 – Isabella I issued an edict outlawing Islam in the Crown of Castile, forcing virtually all her Muslim subjects to convert to Christianity.
- May 3 – Portuguese navigator João da Nova discovers the uninhabited island of Saint Helena.
- May 11 – Christopher Columbus leaves Cadiz, Spain for his fourth and final trip to the New World. He explores Central America, and discovers St. Lucia (possibly), the Isthmus of Panama, Honduras, and Costa Rica.
- July – Ismail I becomes Shah of Persia.
- August 14 – Christopher Columbus lands at Trujillo, and names the country 'Honduras'.
- September – A Greek and Italian parallel text edition of Herodotus' Histories, done for Count Matteo Maria Boiardo, is published in Venice by Aldus Manutius.
- September 18 – Christopher Columbus lands at Costa Rica.
- September 29; The Wedding of Vladislaus II of Bohemia and Hungary and Anne of Foix-Candale
- October 1 – An annular solar eclipse occurs.
- November 7 – Columbus reaches the coast of Honduras, and passes south to Panama.
- December 26 – Cesare Borgia kills Ramiro d'Orco; this incident is referenced in Machiavelli's The Prince
- December 31 – Cesare Borgia (son of Pope Alexander VI) occupies Urbino, where he imprisons two potentially treacherous allies, Vitellozzo and Oliveretto; he executes them the next morning.
- The first African slaves brought to the New World arrive at the island of Hispaniola (modern-day Haiti and Dominican Republic).
- Bristol merchants return from Newfoundland (first so named this year from a letter) to England, carrying three native people and cod from the Grand Banks.
- Moctezuma II is elected emperor of the Aztecs, following the death of Ahuitzotl.
- Meñli I Giray defeats the Golden Horde and sacks their capital, Sarai.
- Wittenberg University is founded.
- In Germany, Peter Henlein of Nuremberg uses iron parts and coiled springs to build a portable timepiece.
- In Italy, Asher Lämmlein declares that the Jewish Messiah will arrive in the next 6 months, resulting in the year of penance.
- The King's School, Macclesfield, England, is founded by Sir John Percyvale.
- Heinrich Cornelius Agrippa receives the degree of magister artium from the University of Cologne.
- Wilhelm Bombast moves to Villach with his son, Paracelsus.
- January 20 – Seville in Castile is awarded exclusive rights to trade with the New World.
- January 24 – Construction of the Henry VII Chapel at Westminster Abbey begins in the perpendicular style, the final stage of English Gothic art.
- February 11 – Queen Elizabeth of York, wife of Henry VII of England, dies on her 37th birthday, more than a week after giving birth to her daughter Katherine Tudor, who died the previous day.
- February 13 – Challenge of Barletta: Thirteen Italian knights defeat thirteen French knights, near Barletta.
- February 23 – French–Spanish Wars in Italy – Battle of Ruvo: The Spanish defeat the French.
- April 21 – Battle of Seminara: Spanish forces under Fernando de Andrade de las Mariñas defeat the French under Bernard Stewart, 4th Lord of Aubigny.
- April 28 – Battle of Cerignola: Spanish forces under Gonzalo Fernández de Córdoba defeat the French under Louis d'Armagnac, Duke of Nemours, who is killed (considered to be the first battle in history won by gunpowder small arms).
- May 10 – Christopher Columbus discovers the Cayman Islands, which he names Las Tortugas, after the numerous sea turtles there.
- May 13 – Naples is captured by the Spanish.
- May 20 (Feast of the Ascension) – Ascension Island is first definitively sighted, by Portuguese admiral Afonso de Albuquerque.
- May 28
- July 23 – Orbital calculations suggest that on this day, Pluto moves outside Neptune's orbit, remaining there for 233 years.
- July 30 – Saint Helena is first definitively sighted, by ships of Portuguese navigator Estêvão da Gama returning from the East.
- August 8 – King James IV of Scotland marries Margaret Tudor, daughter of King Henry VII of England, at Holyrood Abbey, Edinburgh, Scotland.
- August 20 – Stephen III of Moldavia concludes a treaty with Sultan Bayezid II, preserving Moldavia's self-rule at the cost of an annual tribute to the Ottoman Empire.
- September 22 – Pope Pius III (Francesco Todeschini Piccolomini) succeeds Alexander VI as the 215th pope, but dies on October 18.
- October 30 – Queen Isabella I of Spain prohibits violence against indigenous peoples in the New World.
- October 31 – Pope Julius II succeeds Pius III, as the 216th pope (some sources list November 1 as the date of election).
- December 29 – Battle of Garigliano, near Gaeta, Italy: Spanish forces under Gonzalo Fernández de Córdoba defeat a French–Italian mercenary army under Ludovico II, Marquess of Saluzzo; the French forces withdraw to Gaeta.
- Vasco da Gama establishes India's first Portuguese fortress, at Cochin.
- Mariotto Albertinelli paints The Visitation.
- Hieronymus Bosch works on the triptych The Garden of Earthly Delights.
- Leonardo da Vinci probably starts work on painting the Mona Lisa in Florence.
- The book The Imitation of Christ by Thomas à Kempis is re-published in an English translation.
- The pocket handkerchief comes into general use in polite European society.
- From this year until 1650, sixteen million kilograms of silver and 185,000 kilograms of gold will enter the port of Seville.
- January 1 – French troops of King Louis XII surrender Gaeta to the Spanish, under Gonzalo Fernández de Córdoba.
- January 21 – After the death of Sten Sture the Elder on December 14 the year before, Svante Nilsson is elected the new Regent of Sweden.
- January 31 – Treaty of Lyon: France cedes Naples to Ferdinand II of Aragon, who becomes King of Naples as Ferdinand III.
- February 29 – Christopher Columbus uses his knowledge of a lunar eclipse this night, to convince the indigenous Jamaican people to provide him with supplies.
- April 1 – English guilds become subject to state control.
- April 23 – Maximilian I, Holy Roman Emperor, routes troops to Bavaria.
- September 8 – Michelangelo's sculpture of David is completed in Florence.
- September 13 – Queen Isabella and King Ferdinand issue a Royal Warrant for the construction of Capilla Real, a Royal Chapel, to be built.
- September 22 – A settled engagement is arranged, between Karel of Luxembourg and Claudia the Beaujeu.
- September 22 – Treaty of Blois: Philip I of Castile, Maximilian I and Louis XII agree to terms.
- October 12 – Isabella I of Castile signs her testament.
- November 7 – Christopher Columbus returns to Spain from his fourth voyage, during which he and his younger son, Ferdinand, explored the coast of Central America from Belize to Panama.
- November 26 – Isabella I of Castile, Catholic Queen of Castile and Aragon, dies, ending her patronage for Columbus. The Crown of Castile passes to her daughter Joanna.
- December 8 (approximate date) – Islamic scholar Ahmad ibn Abi Jum'ah issues the Oran fatwa for Muslims in Spain (1 Rajab 910 AH in Hijri calendar, Gregorian date is approximate).
- December 24 – The Alvsson's rebellion was crushed at Olsborg Castle in Båhuslen.
- Babur besieges and captures Kabul.
- Islamization of the Sudan region: A Funj leader, Amara Dunqas, founds the Sultanate of Sennar.
- Sheikh Ahmad, final leader of the Great Horde, is last heard of as a Lithuanian prisoner at Vilnius.
- Juan de la Cosa begins his first independent voyage, to the Isthmus of Panama.
- In Florence, Leonardo da Vinci and Niccolò Machiavelli become involved in a scheme to divert the Arno River, cutting the water supply to Pisa to force its surrender: Colombino, the project foreman, fails to follow da Vinci’s design, and the project is a major failure.
- Venetian ambassadors suggest to Turkey the construction of a Suez Canal.
- Aldus Manutius publishes his edition of Demosthenes in Venice.
- Matthias Grünewald paints a Crucifixion.
- The Signoria of Florence commissions both Leonardo da Vinci and Michelangelo to paint the walls of the Grand Council Chamber in the Palazzo Vecchio.
- Raphael paints The Marriage of the Virgin, which exemplifies some major principles of High Renaissance art.
- June 19 – Zhengde Emperor ascends the throne of the Ming Dynasty.
- June 27 – The future King Henry VIII of England repudiates his engagement to Catherine of Aragon, at his father's command.
- July 2 – Martin Luther, then 22, vows to become a monk in a moment of terror, due to a near lightning strike during a thunderstorm, near the village of Stotternheim.
- July – The Kalmar Bloodbath takes place in Kalmar, Sweden.
- July 17 – Luther enters the monastic life, at an Augustinian cloister in Erfurt.
- July 24 – Travelling to India, a group of Portuguese explorers sack the city-state of Kilwa in East Africa, killing the king for failing to pay tribute.
- November 6 – Vasili III succeeds Ivan III, as Grand Prince of Muscovy.
- December 18 – John IX van Horne, prince-bishop of Lièges, Belgium, is executed.
- A Portuguese fleet attacks Kilwa, and then Mombasa. The Portuguese then attempt to monopolize the trade in the east African ports, but are unable to maintain control (by the late 16th century, Swahili groups regain control of several ports from the Portuguese).
- Portuguese merchants establish factories on the east coast of Africa.
- Portuguese explorers under Dom Lourenço d'Almeida reach Colombo, Sri Lanka, and send envoys to the King of Kotte; they also reach the Comoros.
- Bermuda is discovered by Spanish explorer Juan de Bermúdez.
- King Alexander of Poland signs the Nihil novi Act, making Poland a Nobles' Democracy.
- Poland prohibits peasants from leaving their lands, establishing serfdom.
- Christ's College, Cambridge, is re-founded, receiving its charter from Lady Margaret Beaufort.
- Judah Abravanel becomes personal physician to the viceroy of Naples.
- Battle of Achnashellach in Scotland: The Cameron Clan emerges victorious over several other clans.
- The M8.2–8.8 Lo Mustang earthquake strikes Nepal, causing severe damage in Kathmandu, western Nepal, and some parts of the Indo-Gangetic plain.
- 1505 (or 1506) – Portuguese explorer Gonçalo Álvares is the first to sight what will later be known as Gough Island, in the South Atlantic.
- January 14 – The classical statue of Laocoön and His Sons is unearthed in Rome. On the recommendation of Giuliano da Sangallo and Michelangelo, Pope Julius II purchases it, and places it on public display in the Vatican a month later.
- January 22 – The Swiss Guard arrives at the Vatican, to serve as permanent ceremonial and palace guards under Pope Julius II.
- April 18 – Pope Julius II lays the foundation stone of the new (current) St. Peter's Basilica in Rome, replacing the Old St. Peter's Basilica.
- April 19–21 – Lisbon Massacre: Thousands of Jews are tortured and killed by Catholics in Lisbon, Portugal.
- August 6 – Battle of Kletsk: The Grand Duchy of Lithuania defeats the Tatars of the Crimean Khanate.
- August 19 – Sigismund I the Old succeeds his brother, as king of Poland.
- November 6 – Pope Julius II personally leads his troops into Bologna, retaking the city from the excommunicated tyrant Giovanni II Bentivoglio.
- The Portuguese mariner Tristão da Cunha sights the islands of Tristan da Cunha, naming them after himself.
- In Ming Dynasty China, the costs of the courier system are met by a tax in silver on land, instead of corvée labor service.
- Duarte Barbosa returns to Lisbon.
- Johannes Trithemius becomes abbot of the monastery of St. Jacob, at Würzburg.
- Leonardo da Vinci completes most of his work on the Mona Lisa.
- April 25 – Martin Waldseemüller publishes his Cosmographiae Introductio ("Introduction to Universal Cosmography") and accompanying wall map, the first to show the Americas as a separate continent, naming them in honour of Amerigo Vespucci, his friend and idol.
- July 4 – Martin Luther is ordained a priest of the Catholic Church.
- August 20 – Guru Nanak Dev becomes the first guru, and leader, of the Sikh religion.
- The Timurid Dynasty ends, when Uzbeks under Muhammad Shaybani capture the capital, Herat, and Emir Badi' al-Zaman Mirza flees.
- The Portuguese occupy Mozambique, and the islands of Socotra and Lamu.
- Cardinal Cisneros is appointed major inquisitor of Castile.
- King Henry VII of England prosecutes lords for keeping private armies, which might threaten his régime.
- King James IV grants a patent for the first printing press in Scotland, to Walter Chapman and Andrew Myllar.
- Raphael paints The Deposition, among other works.
- The Aztec New Fire ceremony is held for the last time (according to Bernardino de Sahagún).
- August – Lebna Dengel succeeds his father Na'od, as Emperor of Ethiopia. Due to his young age, his grandmother Eleni acts as regent.
- December – Michelangelo begins painting the Sistine Chapel ceiling in the Holy See of Rome, on a commission by Pope Julius II (signed May 10).
- December 10 – The League of Cambrai is formed as an alliance against the Republic of Venice, between Pope Julius II, Louis XII of France, Maximilian I, Holy Roman Emperor and Ferdinand II of Aragon.
- February 3 – Battle of Diu: The Portuguese defeat a coalition of Indians, Muslims and Italians.
- April 21 – Henry VIII becomes King of England (for 38 years) on the death of his father, Henry VII.
- April 27 – Pope Julius II places Venice under interdict and excommunication, for refusing to cede part of Romagna to papal control.
- May 14 – Battle of Agnadello: French forces defeat the Venetians.
- June 11
- June 19 – Brasenose College, Oxford is founded by a lawyer, Sir Richard Sutton, of Prestbury, Cheshire, and the Bishop of Lincoln, William Smyth.
- June 24 – King Henry VIII of England and Queen Consort Catherine of Aragon are crowned.
- July 26 – Krishnadevaraya ascends the throne of the Vijayanagara Empire.
- September 10 – The Constantinople earthquake destroys 109 mosques, and kills an estimated 10,000 people.
- September 11 – Portuguese fidalgo Diogo Lopes de Sequeira becomes the first European to reach Malacca, having crossed the Gulf of Bengal.
- Erasmus writes his most famous work, In Praise of Folly.
- The Royal Dano-Norwegian Navy is founded.
- Royal Grammar School, Guildford, is founded by Robert Beckingham.
- St Paul's School is founded by John Colet, Dean of St Paul's Cathedral, London.
- Queen Elizabeth's Grammar School, Blackburn, is founded as a grammar school for boys.
- Afonso de Albuquerque becomes the governor of the Portuguese settlements in India.
- The earliest known pocket watch is made at Nuremberg, Germany by Peter Henlein.
- Albuquerque, Afonso de (2001). The commentaries of the great Afonso Dalboquerque, second viceroy of India, Adamant Media Corporation, p.xx. Issue 55. ISBN 1-4021-9511-7.
- "Ascension History". Mysterra Magazine. Retrieved December 9, 2011.
- Lea, Henry Charles (1901). The Moriscos of Spain: Their Conversion and Expulsion. Lea Brothers & Company. p. 40.
- "Ivan III Vasil'yevich (1440–1505)". Russia – Rulers. Xenophon Group International. Retrieved July 22, 2013.
- The traditional May 21 date is the Protestant feast day for Saint Helena (empress) and would not have been marked this day by the Portuguese because they were members of the Catholic Church and also because the island was discovered before the Reformation started. The discovery date is quoted as 3 May during the 16th/17th centuries, corresponding to the Catholic Feast day of the True Cross, a date that is closely linked to the name of Saint Helena. Bruce, Ian (2015). "St Helena Day" (PDF). Wirebird: The Journal of the Friends of St Helena (44): 32–46.
- "History of St. Lucia". Retrieved May 6, 2011.
- The New Encyclopædia Britannica: Micropædia, Encyclopædia Britannica, 1991, ISBN 978-0-85229-529-8, p. 295.
- Fabyan, Robert (1516). The New Chronicles of England and France.
- Nansen, Fridtjof. In Northern Mists: Arctic Exploration in Early Times.
- Valente, Michaela (2006). "Agrippa, Heinrich Cornelius". In Hanegraaff, Wouter J. Dictionary of Gnosis and Western Esotericism. Leiden: Brill. pp. 4–8. ISBN 90-04-15231-8.
- Palmer, Alan; Veronica (1992). The Chronology of British History. London: Century Ltd. pp. 137–140. ISBN 0-7126-5616-2.
- "Ascension History". Mysterra Magazine. Retrieved 2011-12-09.
- Schulenburg, A. H. (Spring 2002). "The discovery of St Helena: the search continues". Wirebird: the Journal of the Friends of St Helena. 24: 13–19.
- Leite, Duarte (1960). História dos Descobrimentos. II. Lisbon: Edições Cosmos. p. 206.
- da Montalboddo, Fracanzio (1507). Paesi Nuovamente Retovati & Nuovo Mondo da Alberico Vesputio Fiorentino Intitulato. Venice.
- Frieda 2013, p. 275 & 276.
- "Watercolour - Copy after The Visitation (The meeting of Mary and Elizabeth), Mariotto Albertinelli in the Uffizi (Florence)". m.vam.ac.uk. Retrieved 6 May 2018.
- "Historical Events for Year 1506 | OnThisDay.com". Historyorb.com. Retrieved 2016-06-28.
- Cheney, C. R.; Cheney, Christopher Robert; Jones, Michael (2000). A Handbook of Dates: For Students of British History. Cambridge University Press. pp. 37–38. ISBN 9780521778459.
- "On April 27, 1509, Pope Julius II excommunicated the..." tribunedigital-chicagotribune. Retrieved 19 June 2018.