- 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.
- November 4 – Afonso de Albuquerque becomes the governor of the Portuguese settlements in India.
- Erasmus writes his most famous work, In Praise of Folly.
- St Paul's School, London is founded by John Colet, Dean of St Paul's Cathedral.
- Royal Grammar School, Guildford, England, is founded under the will of Robert Beckingham.
- Queen Elizabeth's Grammar School, Blackburn, England, is founded as a grammar school for boys.
- Basil Solomon becomes Syriac Orthodox Maphrian of the East.
- January 1 – Guillaume Le Testu, French privateer (d. 1573)
- January 2 – Henry of Stolberg, German nobleman (d. 1572)
- January 3 – Gian Girolamo Albani, Italian Catholic cardinal (d. 1591)
- January 25 – Giovanni Morone, Italian Catholic cardinal (d. 1580)
- February 2 – John of Leiden, Dutch Anabaptist leader (d. 1536)
- February 10 – Vidus Vidius, Italian surgeon and anatomist (d. 1569)
- March 27 – Wolrad II, Count of Waldeck (1539–1575) (d. 1575)
- April 23 – Afonso of Portugal, Roman Catholic cardinal (d. 1540)
- July 4 – Magnus III of Mecklenburg-Schwerin, Lutheran bishop of the Prince-Bishopric of Schwerin (d. 1550)
- July 10 – John Calvin, French religious reformer (d. 1564)
- July 25 – Philip II, Count of Nassau-Saarbrücken, German noble (d. 1554)
- August 3 – Étienne Dolet, French scholar and printer (d. 1546)
- August 7 – Joachim I, Prince of Anhalt-Dessau, German prince (d. 1561)
- August 25 – Ippolito II d'Este, Italian cardinal and statesman (d. 1572)
- October 20 – Arthur Stewart, Duke of Rothesay, Scottish prince (d. 1510)
- November 4 – John, Duke of Münsterberg-Oels and Count of Glatz (d. 1565)
- date unknown
- John Erskine of Dun, Scottish religious reformer (d. 1591)
- Stanisław Odrowąż, Polish noble (d. 1545)
- Anneke Esaiasdochter, Dutch Anabaptist (d. 1539)
- Gonzalo Jiménez de Quesada, Spanish conquistador (d. 1579)
- Bernardino Telesio, Italian philosopher and natural scientist (d. 1588)
- Kamran Mirza, Mughal prince (d. 1557)
- January – Adam Kraft, sculptor and architect
- January 27 – John I, Count Palatine of Simmern (1480–1509) (b. 1459)
- March 14 – Giovanni Antonio Sangiorgio, Italian cardinal
- April 21 – King Henry VII of England (b. 1457)
- April 27 – Margaret of Brandenburg, abbess of the Poor Clares monastery at Hof (b. 1453)
- May 28 – Caterina Sforza, countess and regent of Forli (b. 1463)
- June 29 – Margaret Beaufort, Countess of Richmond and Derby, mother of Henry VII of England (b. 1443)
- July 11 – William II, Landgrave of Hesse (b. 1469)
- July 16
- December 1 – Lê Uy Mục, 8th king of the later Lê Dynasty of Vietnam (b. 1488)
- date unknown