1516 1517 1518 - 1519 - 1520 1521 1522
1480s 1490s 1500s - 1510s - 1520s 1530s 1540s
- January 1 – Ulrich Zwingli preaches for the first time as people's priest of the Great Minister in Zurich
- March 4 – Hernán Cortés lands in Mexico
- April 21 – Hernán Cortés lands in Veracruz, Veracruz
- June 28 – Charles I of Spain becomes Charles V, Holy Roman Emperor (rules until 1556).
- July 4 – Martin Luther joins the debate regarding papal authority against John Eck at Leipzig.
- August 15 – Panama City is founded.
- September 20 – Ferdinand Magellan leaves Europe to circumnavigate the world.
- October 12 – Hernán Cortés and his men, accompanied by 3,000 Tlaxcalans, entered Cholula.
- November 8 – Hernán Cortés enters Tenochtitlan and the court of Aztec ruler Moctezuma.
- Erasmus publishes his Colloquia.
- Martin Luther questions the infallibility of papal decrees.
- The artistic form appears in Georgia and spreads.
- The Spanish find Barbados.
- The first civil revolt in Anatolia takes place, led by Alevi preacher Celâl.
- Cacao comes to Europe.
- Havana moves from the southern to the northern part of Cuba.
- The St. Olav Church is completed in Tallinn, Estonia.
- According to Wang Yangming (1472–1529), the Ming Dynasty philosopher and governor of Jiangxi, China, he intends to use fo–lang–ji cannons in suppressing the rebellion of Prince Zhu Chenhao in this year. This is most likely the earliest reference in China to the breech-loading Frankish culverin.
- A large pandemic spreads from the Greater Antilles into Central America, and perhaps as far as Peru in South America. This widespread epidemic kills off much of the indigenous populations in these areas. According to historian Alfred W. Crosby Jr. in his The Columbian Exchange: Biological and Cultural Consequences of 1492, this outbreak is the first widely documented epidemic in the New World.
- Central Mexico Amerindians' population – 25.3 million.
- Postclassic period ends in Mesoamerica.
- The first recorded fatal accident involving a gun in England was recorded at Welton, East Riding of Yorkshire.
- 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)
- 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 24 – Theodore Beza, French theologian (d. 1605)
- July 22 – Pope Innocent IX (d. 1591)
- date unknown
- Thoinot Arbeau, French priest and author (d. 1596)
- Johannes Goropius Becanus, Dutch physician, linguist, and humanist (d. 1572)
- Nicholas Grimald, English poet (d. 1562)
- Edmund Grindal, Archbishop of Canterbury (d. 1583)
- Ikeda Nagamasa, Japanese military commander (d. 1563)
- Edwin Sandys, English prelate (d. 1588)
- Imagawa Yoshimoto, Japanese warlord
- Stanisław Zamoyski, Polish nobleman (d. 1572)
- January 12 – Maximilian I, Holy Roman Emperor (b. 1459)
- January 21 – Vasco Núñez de Balboa, Spanish explorer (b. 1475)
- March 29 – Francesco II Gonzaga, Marquess of Mantua (b. 1466)
- May 2 – Leonardo da Vinci, Italian inventor and painter (b. 1452)
- May 4 – Lorenzo II de' Medici, Duke of Urbino (b. 1492)
- June 24 – Lucrezia Borgia, Duchess of Ferrara (b. 1480)
- August 11 – Johann Tetzel, German opponent of the Reformation (b. 1465)
- August 23 – Philibert Berthelier, Swiss patriot (b. c. 1465)
- September 10 – John Colet, English churchman and educator (b. 1467)
- date unknown
- William Grocyn, English scholar (b. 1446)
- Lorenz von Bibra, Prince-Bishop of the Bishopric of Würzburg (b. 1459)
- Cho Kwangjo, Korean scholar (b. 1482)
- Bars Bolud Jinong, Mongol khan (b. 1490)
- Ambrosius Holbein, German painter (b. 1494)
- Alonso Álvarez de Pineda, Spanish explorer and cartographer (b. 1494)