1521

January–June

• January 3 - Pope Leo X excommunicates Martin Luther, in the papal bull Decet Romanum Pontificem.
• January 22 - Charles V, Holy Roman Emperor, opens the Diet of Worms in Worms, Germany.
• January 27 - Suleiman the Magnificent suppresses a revolt by the ruler of Damascus.
• January 28 - The Diet of Worms begins, lasting until May 25.
• February 2 - The Nydala Abbey Bloodbath take place in Nydala Abbey, Sweden.
• March 6
• * Ferdinand Magellan discovers Guam.
• * Martin Luther is summoned to appear before the Diet of Worms.
• March 16 - Ferdinand Magellan reaches the Philippines.
• March 31 - The First Mass in the Philippines is held.
• April - The Battle of Tunmen occurs, in Tuen Mun, where the Ming Dynasty navy defeats the Portuguese navy. Arguably the first Sino-European battle in world history.
• April 7
• * Ferdinand Magellan arrives at Cebu.
• * Martin Luther preaches an inflammatory sermon to students at Erfurt, while on his way to Worms.
• April 16-18 - Martin Luther is examined before Emperor Charles V and the Diet of Worms, where he proclaims, "Here I stand", regarding his belief in the Bible alone, as the standard of Christian doctrine.
• April 24 - Revolt of the Comuneros - Battle of Villalar: Castilian royalists defeat the rebels and execute their three leaders.
• April 26 - Martin Luther leaves Worms and disappears for a year - he is rumored to be murdered, but is actually in hiding at the Wartburg castle.
• April 27 - Battle of Mactan: Ferdinand Magellan is killed in the Philippines.
• May - The Italian War of 1521–26 breaks out between Charles V, Holy Roman Emperor, and Francis I of France.
• May 17 - Edward Stafford, 3rd Duke of Buckingham, is executed for treason in London.
• May 20 - Battle of Pampeluna: The French defeat the Spanish.
• May 25 - The Diet of Worms ends when Charles V, Holy Roman Emperor issues the Edict of Worms, declaring Martin Luther an outlaw.
• May 27 - Jiajing Emperor ascends the throne of the Ming Dynasty.
• June 25 - Suleiman the Magnificent begins the siege of Belgrade.
• June 29 or 30 - The oldest surviving dateable document written primarily in the Romanian language: Neacșu's letter, written by a trader from Câmpulung, to Johannes Benkner, the mayor of Brașov, warning that the Ottoman Empire is preparing its troops to cross into Wallachia and Transylvania; the script used is Romanian Cyrillic.
• June 30 - Battle of Esquiroz: French forces under Henri d'Albret, exiled King of Navarre, are defeated by the Spanish, and forced to abandon their attempt to recover Henri's kingdom.

  July–December

• July - Pfaffensturm: Students rebel against priests in Erfurt.
• August 8 - Fall of Tenochtitlan: Hernán Cortés and allied local indigenous peoples of the Americas defeat the Aztec forces of Cuauhtémoc, the last Tlatoani, at Tenochtitlan in the Valley of Mexico.
• August 13 - Fall of Tenochtitlan: Cuauhtémoc surrenders to Cortés, thus incorporating the Aztec Empire into the Spanish Empire and ending the Late Postclassic period in Mesoamerica.
• August 29 - Belgrade is captured by the Ottoman army of Suleiman the Magnificent.
• November 23 - Spanish–German–Papal forces under Prospero Colonna force French Marshal Odet de Lautrec to abandon Milan.
• December 27 - The Zwickau prophets arrive in Wittenberg, disturbing the peace and preaching the Apocalypse.

  Date unknown

• Jacopo Berengario da Carpi publishes Commentaria cum amplissimus additionibus super anatomiam Mundini in Bologna, including observation of the vermiform appendix.
• San Juan Bautista is founded in the archipelago of Puerto Rico.
• The Principality of Ryazan is annexed by the Grand Duchy of Moscow.

  Births

• March 21 - Maurice, Elector of Saxony
• April 5 - Francesco Laparelli, Italian architect
• April 14 - Johann Marbach, German theologian
• April 18 - François de Coligny d'Andelot, French general
• May 8 - Petrus Canisius, Dutch Jesuit
• May 10 - John Ernest, Duke of Saxe-Coburg,
• June 18 - Maria of Portugal, Duchess of Viseu, daughter of King Manuel I
• June 21 - John II, Duke of Schleswig-Holstein-Haderslev
• August 4 - Pope Urban VII
• August 19 - Lodovico Guicciardini, Italian historian
• October 1 - Frederick Magnus I, Count of Solms-Laubach,
• November 22 - Edmund Sheffield, 1st Baron Sheffield, English baron
• November 29 - Marcantonio Maffei, Italian Catholic archbishop and cardinal
• December 1 - Takeda Shingen, Japanese warlord
• December 13 - Pope Sixtus V
• date unknown
• * Anne Askew, English Protestant martyr
• * John Aylmer, English divine
• * Sue Harukata, Japanese retainer and later daimyō under Ouchi Yoshitaka
• * Thomas Chaloner, English statesman and poet
• * Philippe de Monte, Flemish composer
• * Rokkaku Yoshikata, Japanese daimyō
• * Thomas Wyatt the Younger, English rebel
• possible
• * Catherine Howard, Fifth Queen of Henry VIII of England,

  Deaths

• January 6 - Cardinal William de Croÿ
• March 15 - John II, Duke of Cleves
• April 20 - Zhengde Emperor of China
• April 24 - Spanish rebels
• * Juan López de Padilla
• * Juan Bravo
• * Francisco Maldonado
• April 27 - Ferdinand Magellan, Portuguese explorer
• April 28 - Suzanne, Duchess of Bourbon
• May 10 - Sebastian Brant, German humanist and satirist
• May 17 - Edward Stafford, 3rd Duke of Buckingham
• June 15 - Tamás Bakócz, Hungarian Catholic cardinal and statesman
• June 22 - Leonardo Loredan, Doge of Venice
• July 9 - Raffaele Riario, Italian cardinal
• July - Juan Ponce de León, Spanish conquistador
• August 27 - Josquin des Prez, Flemish composer
• October 7 - Margaret of Anhalt-Köthen, Princess of Anhalt by birth, Duchess consort of Saxony
• October 22 - Edward Poynings, Lord Deputy to King Henry VII of England
• October 24 - Robert Fayrfax, English Renaissance composer
• November 2 - Margaret of Lorraine, French Duchess of Alençon, Roman Catholic nun and blessed
• December 1 - Pope Leo X
• December 13 - King Manuel I of Portugal
• December 21 - Domenico Spadafora, Italian Roman Catholic priest and blessed
• date unknown
• * Cuauhtémoc, 11th Tlatoani of Tenochtitlan, 1520-1521, hanged