1516

January–June

• January - Juan Díaz de Solís discovers the Río de la Plata.
• 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–December

• 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 : 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 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.

  Date unknown

• 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, 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.

  Births

• January 1 - Margaret Leijonhufvud, queen of Gustav I of Sweden
• January 14 - Herluf Trolle, Danish admiral
• January 16 - Bayinnaung, King of Burma
• February 2 - Girolamo Zanchi, Italian theologian
• February 16 - Prospero Spani, Italian sculptor
• February 18 - Queen Mary I of England, daughter of King Henry VIII of England and Queen Catherine of Aragon
• March 15 - Alqas Mirza, Safavid prince
• March 26 - Conrad Gessner, Swiss naturalist
• April 16 - Tabinshwehti, King of Burma
• April 23 - Georg Fabricius, Protestant German poet
• June 28 - Charles Blount, 5th Baron Mountjoy, English courtier and patron of learning
• July 27 - Emilie of Saxony, German nobleman
• July 28 - William, Duke of Jülich-Cleves-Berg, German nobleman
• August 13 - Hieronymus Wolf, German historian
• September 2 - Francis I, Duke of Nevers
• September 21 - Matthew Stewart, 4th Earl of Lennox
• October 4 - Archangelo de' Bianchi, Italian cardinal
• October 23 - Charlotte of Valois, French princess
• October 27 - Ruy Gómez de Silva, Portuguese noble
• November 5 - Martin Helwig, German cartographer of Silesia
• December 21 - Giuseppe Leggiadri Gallani, Italian poet and dramatist
• date unknown
• * Antonio Bernieri, Italian painter during the Renaissance period
• * John Foxe, biographer
• * Manco Inca Yupanqui, ruler of the Inca
• * Canghali of Kazan, khan of Qasim and Kazan
• * Margaretha Coppier, Dutch heroine
• * Shri Gusainji, son of Shri Vallabhacharyaji.
• probable
• * James Hamilton, Duke of Châtellerault

  Deaths

• January 20 - Juan Díaz de Solís, Spanish navigator and explorer
• January 23 - King Ferdinand II of Aragon
• February 4 - Anthony of Supraśl, Polish Orthodox priest and saint
• March 13 - Vladislaus II, king of Bohemia, Hungary and Croatia
• March 17 - Giuliano de' Medici, Duke of Nemours, ruler of Florence
• April 25 - John Yonge, English diplomat
• June 14 - King John III of Navarre
• July 10 - Alice FitzHugh, English heir
• July 30 - Johann V of Nassau-Vianden-Dietz, Dutch count
• August 9 - Hieronymus Bosch, Dutch painter
• August 21 - John III of Egmont, Dutch count
• August 24 - Al-Ashraf Qansuh al-Ghuri, Mamluk sultan
• November 26 - Giovanni Bellini, Venetian painter
• December 13 - Johannes Trithemius, German scholar and cryptographer
• date unknown - Giuliano da Sangallo, Florentine sculptor and architect