|Covid-19|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 translation 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 relationships between church and state in France.
October 28 – Battle of Yaunis Khan: Ottoman forces under the Grand Vizier Sinan Pasha defeat the Mameluks 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).
The fall of the Nantan meteorite possibly observed near the city of Nantan, Nandan County, Guangxi (China).
Juan Díaz de Solís discovers the Río de la Plata.
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 established in Augsburg (Bavaria) as the world's oldest social housing complex still in use.
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, 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 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 noble (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, Poet; Dramatist (d. 1590)
Antonio Bernieri, Italian painter during the Renaissance period (d. 1565)
John Foxe, biographer (d. 1587)
Manco Inca Yupanqui, ruler of the Inca (d. 1544)
Canghali of Kazan, khan of Qasim and Kazan
Shri Gusainji, son of Shri Vallabhacharyaji.
James Hamilton, Duke of Châtellerault (d. 1572)
January 20 – Juan Díaz de Solís, Spanish navigator and explorer (b. 1470)
January 23 – King Ferdinand II of Aragon (b. 1452)
February 4 – St. Anthony of Supraśl
March 13 – King Vladislaus II of Bohemia and Hungary (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 30 – Johann V of Nassau-Vianden-Dietz (b. 1455)
August – Hieronymus Bosch, Dutch painter (b. 1450)
December 13 – Johannes Trithemius, German scholar and cryptographer (b. 1462)
date unknown – Giuliano da Sangallo, Italian sculptor and architect (b. 1443)
probable – Giovanni Bellini, Italian painter (b. 1430)
Year 1516 (MDXVI) was a leap year starting on Tuesday (link will display the full calendar) of the Julian calendar.