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|Ab urbe condita||2269|
|Balinese saka calendar||1437–1438|
|English Regnal year||7 Hen. 8 – 8 Hen. 8|
|Chinese calendar||乙亥年 (Wood Pig)|
4212 or 4152
— to —
丙子年 (Fire Rat)
4213 or 4153
|- Vikram Samvat||1572–1573|
|- Shaka Samvat||1437–1438|
|- Kali Yuga||4616–4617|
|Japanese calendar||Eishō 13|
|Minguo calendar||396 before ROC|
|Thai solar calendar||2058–2059|
1642 or 1261 or 489
— to —
1643 or 1262 or 490
|Wikimedia Commons has media related to 1516.|
- January – Juan Díaz de Solís discovers the Río de la Plata (in future Argentina).
- January 23 – With the death of Ferdinand II of Aragon, his grandson, Charles of Ghent, becomes King of Spain.
- March 1 – Desiderius Erasmus publishes a new Greek edition of the New Testament, Novum Instrumentum omne, in Basel.
- April 23 – The Reinheitsgebot is instituted in Ingolstadt, Bavaria, regulating the purity of beer permissible for sale.
- July – Selim I of the Ottoman Empire declares war on the Mamluk Sultanate of Cairo and invades Syria.
- August 13 – The Treaty of Noyon is signed. Francis I of France recognizes Charles I of Spain's claim to Naples, and Charles recognizes Francis's claim to Milan.
- August 18 – King Francis I of France and Pope Leo X sign the Concordat of Bologna, agreeing on the relationship between church and state in France.
- August 24– Battle of Marj Dabiq (Ottoman–Mamluk War (1516–17)): The Ottoman Sultan Selim I defeats the mamluk forces commanded by the sultan Al-Ashraf Qansuh al-Ghuri.
- October 28 – Battle of Yaunis Khan (Ottoman–Mamluk War (1516–17)): Ottoman forces under the Grand Vizier Sinan Pasha defeat the Mamluks near Gaza.
- December 4 – Treaty of Brussels: Peace is declared between the Kingdom of France and the Holy Roman Empire.
- c. December – Thomas More's most famous work, Utopia, completed this year, is published in Leuven (in Latin).
- Italian explorer Rafael Perestrello, a cousin of Christopher Columbus, commands an expedition from Portuguese Malacca to land on the shores of mainland southern China, and trade with Chinese merchants at Guangzhou, during the Ming Dynasty.
- Portuguese soldier Fernão Lopes becomes the first known permanent inhabitant of Saint Helena.
- The Venetian Ghetto is instituted, the first ghetto anywhere in the world.
- Leonardo da Vinci accepts Francis I's invitation to France.
- Gillingham School is founded, the oldest in Dorset, England.
- The predecessor of the Royal Mail, known as the Master of the Posts, is established by Henry VIII of England.
- Fuggerei is established in Augsburg (Bavaria), as the world's oldest social housing complex still in use.
- The fall of the Nantan meteorite is possibly observed near the city of Nantan, Nandan County, Guangxi (China).
- January 1 – Margaret Leijonhufvud, queen of Gustav I of Sweden (d. 1551)
- January 14 – Herluf Trolle, Danish admiral (d. 1565)
- January 16 – Bayinnaung, King of Burma (d. 1581)
- February 2 – Girolamo Zanchi, Italian theologian (d. 1590)
- February 16 – Prospero Spani, Italian sculptor (d. 1584)
- February 18 – Queen Mary I of England, daughter of King Henry VIII of England and Queen Catherine of Aragon (d. 1558)
- March 15 – Alqas Mirza, Safavid prince (d. 1550)
- March 26 – Conrad Gessner, Swiss naturalist (d. 1565)
- April 16 – Tabinshwehti, King of Burma (d. 1550)
- April 23 – Georg Fabricius, Protestant German poet (d. 1571)
- June 28 – Charles Blount, 5th Baron Mountjoy, English courtier and patron of learning (d. 1544)
- July 27 – Emilie of Saxony, German nobleman (d. 1591)
- July 28 – William, Duke of Jülich-Cleves-Berg, German nobleman (d. 1592)
- August 13 – Hieronymus Wolf, German historian (d. 1580)
- September 2 – Francis I, Duke of Nevers (d. 1561)
- September 21 – Matthew Stewart, 4th Earl of Lennox (d. 1571)
- October 4 – Archangelo de' Bianchi, Italian cardinal (d. 1580)
- October 23 – Charlotte of Valois, French princess (d. 1524)
- October 27 – Ruy Gómez de Silva, Portuguese noble (d. 1573)
- November 5 – Martin Helwig, German cartographer of Silesia (d. 1574)
- December 21 – Giuseppe Leggiadri Gallani, Italian poet and dramatist (d. 1590)
- date unknown
- January 20 – Juan Díaz de Solís, Spanish navigator and explorer (b. 1470)
- January 23 – King Ferdinand II of Aragon (b. 1452)
- February 4 – Anthony of Supraśl, Polish Orthodox priest and saint
- March 13 – Vladislaus II, king of Bohemia, Hungary and Croatia (b. 1456)
- March 17 – Giuliano de' Medici, Duke of Nemours, ruler of Florence (b. 1449)
- April 25 – John Yonge, English diplomat (b. 1467)
- June 14 – King John III of Navarre (b. 1469)
- July 10 – Alice FitzHugh, English heir (b. 1448)
- July 30 – Johann V of Nassau-Vianden-Dietz, Dutch count (b. 1455)
- August 9 (bur.) – Hieronymus Bosch, Dutch painter (b. 1450)
- August 21 – John III of Egmont, Dutch count (b. 1438)
- August 24 – Al-Ashraf Qansuh al-Ghuri, Mamluk sultan (b. c. 1441)
- November 26 – Giovanni Bellini, Venetian painter (b. 1430)
- December 13 – Johannes Trithemius, German scholar and cryptographer (b. 1462)
- date unknown – Giuliano da Sangallo, Florentine sculptor and architect (b. 1443)