1521

January–June

• January 3 – Pope Leo X excommunicates Martin Luther, in the papal bull Decet Romanum Pontificem.^[1]
• January 22 – Charles V, Holy Roman Emperor, opens the Diet of Worms in Worms, Germany.^[2]
• January 27 – Suleiman the Magnificent suppresses a revolt by the ruler of Damascus, Janbirdi al-Ghazali.^[3]
• February 2 – The Nydala Abbey Bloodbath takes place at Nydala Abbey, Sweden; the abbot and many monks are murdered by Danes.^[4]
• March 6
  • Ferdinand Magellan makes the first European contact with Guam,^[5] most likely landing in Tumon.^[6]
  • Martin Luther is summoned to appear before the Diet of Worms.^[7]
• March 16 – Ferdinand Magellan reaches the Philippines, in eastern Samar.^[8]
• March 31 – The First Mass in the Philippines is held.^[9]
• April or May – Battle of Tunmen in Tuen Mun (present-day Hong Kong): The Ming Dynasty navy defeats the Portuguese navy^[10] (arguably the first Sino-European battle in world history).
• April 7
  • Ferdinand Magellan arrives at Cebu.^[11]
  • Martin Luther preaches an inflammatory sermon to students at Erfurt, while on his way to Worms.^[12]
• April 16–18 – Martin Luther is examined before Emperor Charles V and the Diet of Worms, where he refuses to recant his writings and allegedly proclaims, "Here I stand", regarding his belief in the Bible alone, as the standard of Christian doctrine.
• April 23 – Revolt of the Comuneros – Battle of Villalar: Castilian royalists defeat the rebels.^[13] Juan López de Padilla, Francisco Maldonado, and Juan Bravo are executed the following day as the leaders of the rebels.
• April 26 – Martin Luther leaves Worms and disappears for around a year^[14] – he is rumored to be murdered, but is actually in hiding at the Wartburg castle.^[15]
• April 27 – Battle of Mactan: Ferdinand Magellan is killed in the Philippines.^[16]
• May – The Italian War of 1521–1526 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 Tower Hill.^[17]
• May 20 – Battle of Pampeluna: Allied French-Navarrese forces defeat the Spanish.^[18]
• May 25 – The Diet of Worms ends when Charles V, Holy Roman Emperor issues the Edict of Worms, declaring Martin Luther an outlaw and banning his literature.^[19]
• May 27 – Jiajing Emperor ascends the throne of the Ming dynasty.^[20]
• 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 André de Foix, fighting for the exiled King of Navarre Henri d'Albret, are defeated by the Spanish, and forced to abandon their attempt to recover Henri's kingdom.^[21]

July–December

• July – Pfaffensturm: Students rebel against priests in Erfurt.
• July 15 — San Juan Bautista is founded as the new capital of the archipelago of Puerto Rico.
• August 13 – Fall of Tenochtitlan: Cuauhtémoc surrenders to Cortés,^[22] 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.^[23][24]
• October 25 – Revolt of the Comuneros is crushed.
• 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 spreading the idea of rejecting infant baptism.^[25]

Date unknown

• Jacopo Berengario da Carpi publishes Commentaria cum amplissimus additionibus super anatomiam Mundini in Bologna, including observation of the vermiform appendix.^[26]
• The Grand Duchy of Ryazan is annexed by the Grand Duchy of Moscow.^[27]

• March 21 – Maurice, Elector of Saxony (d. 1553)^[28]
• April 5 – Francesco Laparelli, Italian architect (d. 1570)^[29]
• April 14 – Johann Marbach, German theologian (d. 1581)^[30]
• April 18 – François de Coligny d'Andelot, French general (d. 1569)^[31]
• May 8 – Petrus Canisius, Dutch Jesuit (d. 1597)^[32]
• May 10 – John Ernest, Duke of Saxe-Coburg, (d. 1553)^[33]
• June 8 – Maria of Portugal, Duchess of Viseu, daughter of King Manuel I (d. 1577)^[34]
• June 21 – John II, Duke of Schleswig-Holstein-Haderslev (d. 1580)^[35]
• August 4 – Pope Urban VII (d. 1590)^[36]
• August 19 – Lodovico Guicciardini, Italian historian (d. 1589)^[37][38]
• October 1 – Frederick Magnus I, Count of Solms-Laubach, (d. 1561)
• November 21 – Edmund Sheffield, 1st Baron Sheffield, English baron (d. 1549)^[39]
• November 29 – Marcantonio Maffei, Italian Catholic archbishop and cardinal (d. 1583)^[40]
• December 1 – Takeda Shingen, Japanese warlord (d. 1573)
• December 13 – Pope Sixtus V (d. 1590)^[41]
• date unknown
  • Anne Askew, English Protestant martyr (d. 1546)^[42]
  • John Aylmer, English divine (d. 1594)^[43]
  • Sue Harukata, Japanese retainer and later daimyō under Ōuchi Yoshitaka (d. 1555)^[44]
  • Thomas Chaloner, English statesman and poet (d. 1565)^[45]
  • Philippe de Monte, Flemish composer (d. 1603)^[46]
  • Rokkaku Yoshikata, Japanese daimyō (d. 1598)^[47]
  • Thomas Wyatt the Younger, English rebel (d. 1554)^[48]
• possible
  • Catherine Howard, fifth queen of Henry VIII of England, (b. between 1518 and 1524; d. 1542)^[49]

• January 6 – Cardinal William de Croÿ (b. 1497)^[50]
• January 15 – John II, Duke of Cleves (b. 1458)^[51]
• April 20 – Zhengde Emperor of China (b. 1491)^[52]
• April 24 – Spanish rebels (executed)^[13]
  • Juan López de Padilla
  • Juan Bravo
  • Francisco Maldonado
• April 27 – Ferdinand Magellan, Portuguese explorer (b. 1480)^[53]
• April 28 – Suzanne, Duchess of Bourbon (b. 1491)^[54]
• May 10 – Sebastian Brant, German humanist and satirist (b. 1457)^[55]
• May 17 – Edward Stafford, 3rd Duke of Buckingham (executed) (b. 1478)^[17]
• June 15 – Tamás Bakócz, Hungarian Catholic cardinal and statesman (b. 1442)^[56]
• June 22 – Leonardo Loredan, Doge of Venice (b. 1436)^[57]
• July – Juan Ponce de León, Spanish conquistador (b. 1460)^[58]
• July 9 – Raffaele Riario, Italian cardinal (b. 1461)^[59]
• August 27 – Josquin des Prez, Flemish composer (b. c. 1450)^[60]
• October 7 – Margaret of Anhalt-Köthen, Princess of Anhalt by birth, Duchess consort of Saxony (b. 1494)^[61]
• October 22 – Edward Poynings, Lord Deputy to King Henry VII of England (b. 1459)^[62]
• October 24 – Robert Fayrfax, English Renaissance composer (b. 1464)^[63]
• November 2 – Margaret of Lorraine, French Duchess of Alençon, Roman Catholic nun and blessed (b. 1463)^[64]
• December 1 – Pope Leo X (b. 1475)^[65]
• December 13 – King Manuel I of Portugal (b. 1469)^[66]
• December 21 – Domenico Spadafora, Italian Roman Catholic priest and blessed (b. 1450)^[67]

• 1521 in art
• 
  March–April: Ferdinand Magellan's voyage around the world.
• 
  May 25: Martin Luther outlawed.
• 
  Hans Maler zu Schwaz, Portrait of a beardless man with the inscription:
  "ALS MAN. 1521. ZALT. WAS. ICH. 33. IAR ALT"
  (mutatis mutandis to English: "as we had in 1521, I was 33 years old)
• 
  Lorenzo Lotto, Christ Taking Leave of His Mother