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Year 1519 (MDXIX) was a common year starting on Saturday (link will display the full calendar) of the Julian calendar.
- July 4 – Martin Luther joins the debate regarding papal authority, against Johann Eck at Leipzig.
- July 10 – The Prince of Ning rebellion begins, after Zhu Chenhao declares the Ming dynasty's Zhengde Emperor a usurper, and leads his army north in an attempt to capture Nanjing.
- August 15 – Panama City is founded.
- August 20 – Ming Dynasty Chinese philosopher and general Wang Yangming, governor of Jiangxi, defeats Zhu Chenhao, ending the Prince of Ning rebellion. Wang has expressed the intention of using fo–lang–ji cannons in suppressing the rebellion, probably the earliest reference in China to the breech-loading Frankish culverin.
- September 20 – Ferdinand Magellan departs from Spain with a fleet of five ships, to sail westbound to the Spice Islands.
- October 12 – Hernán Cortés and his men, accompanied by 3,000 Tlaxcalans, enter Cholula.
- November 8 – Hernán Cortés enters Tenochtitlan, and the court of Aztec ruler Moctezuma.
- January 1 – Gómez Pérez Dasmariñas, Spanish colonial administrator (d. 1593)
- January 18 – Isabella Jagiellon, Queen of Hungary (d. 1559)
- February 5 – René of Châlon, Prince of the House of Orange (d. 1544)
- February 15 – Pedro Menéndez de Avilés, first Spanish Governor of Florida (d. 1574)
- February 16 – Gaspard de Coligny, French Huguenot leader (d. 1572)
- February 17 – Francis, Duke of Guise, French soldier and politician (d. 1563)
- February 19 – Froben Christoph of Zimmern, author of the Zimmern Chronicle (d. 1566)
- March 4
- March 17 – Thoinot Arbeau, French priest and author (d. 1595)
- March 22 – Catherine Brandon, Duchess of Suffolk, English noblewoman (d. 1580)
- March 31 – King Henry II of France (d. 1559)
- April 13 – Catherine de' Medici, queen of Henry II of France (d. 1589)
- May 27 – Girolamo Mei, Italian humanist historian (d. 1594)
- June 6 – Andrea Cesalpino, Italian philosopher, physician, and botanist (d. 1603)
- June 12 – Cosimo I de' Medici, Grand Duke of Tuscany (d. 1574)
- June 15 – Henry FitzRoy, 1st Duke of Richmond and Somerset, royal bastard of Henry VIII (d. 1536)
- June 23 – Johannes Goropius Becanus, Dutch physician, linguist, and humanist (d. 1572)
- June 24 – Theodore Beza, French theologian (d. 1605)
- July 20 – Pope Innocent IX (d. 1591)
- September 23 – Francis, Count of Enghien, French military leader (d. 1546)
- October 14 – Marie of Brandenburg-Kulmbach, Princess of Brandenburg-Kulmbach and by marriage Electress Palatine (d. 1567)
- November 9 – Ogasawara Nagatoki, Japanese daimyo (d. 1583)
- November 22 – Johannes Crato von Krafftheim, German humanist and physician (d. 1585)
- date unknown
- January 12 – Maximilian I, Holy Roman Emperor (b. 1459)
- January – Vasco Núñez de Balboa, Spanish explorer (b. 1475)
- February 6 – Lorenz von Bibra, Prince-Bishop of the Bishopric of Würzburg (b. 1459)
- March 29 – Francesco II Gonzaga, Marquess of Mantua (b. 1466)
- April 15 – Henry, Count of Württemberg-Montbéliard (1473–1482) (b. 1448)
- April 18 – Sibylle of Bavaria, Electress Palatine consort (b. 1489)
- May 2 – Leonardo da Vinci, Italian inventor and painter (b. 1452)
- May 4 – Lorenzo de' Medici, Duke of Urbino (b. 1492)
- May 13 – Artus Gouffier, Lord of Boissy, French nobleman and politician (b. 1475)
- June 2 – Philippe de Luxembourg, French Catholic cardinal (b. 1445)
- June 24 – Lucrezia Borgia, Duchess of Ferrara (b. 1480)
- July 13 – Zhu Youyuan, Ming Dynasty politician (b. 1476)
- July 27 – Zanobi Acciaioli, librarian of the Vatican (b. 1461)
- August 11 – Johann Tetzel, German opponent of the Reformation (b. 1465)
- August 23 – Philibert Berthelier, Swiss patriot (b. c. 1465)
- September – John Colet, English churchman and educator (b. 1467)
- date unknown
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