|Covid-19|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 in Sweden.
Ferdinand Magellan discovers Guam.
Martin Luther is summoned to appear before the Diet of Worms.
March 16 – Ferdinand Magellan reaches the Philippines. Starting this year, the Philippines is now one day behind its Asian neighbors.
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.
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 – Ferdinand Magellan is killed in the Philippines, in the Battle of Mactan.
May – 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 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 – Pfaffensturm: Student rebellion 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 (Aztec Emperor), 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.
August 23 – Christian II of Denmark is deposed as king of Sweden and Gustav Vasa is elected new Swedish regent.
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.
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.
March 21 – Maurice, Elector of Saxony (d. 1553)
April 5 – Francesco Laparelli, Italian architect (d. 1570)
April 14 – Johann Marbach, German theologian (d. 1581)
April 18 – François de Coligny d'Andelot, French general (d. 1569)
May 8 – Petrus Canisius, Dutch Jesuit (d. 1597)
May 10 – John Ernest, Duke of Saxe-Coburg, (d. 1553)
June 18 – Maria of Portugal, Duchess of Viseu, daughter of King Manuel I (d. 1577)
June 21 – John II, Duke of Schleswig-Holstein-Haderslev (d. 1580)
August 4 – Pope Urban VII (d. 1590)
August 19 – Lodovico Guicciardini, Italian historian (d. 1589)
October 1 – Frederick Magnus I, Count of Solms-Laubach, (d. 1561)
October 9 – Ottavio Farnese, Duke of Parma (d. 1586)
November 22 – Edmund Sheffield, 1st Baron Sheffield, English Baron (d. 1549)
November 29 – Marcantonio Maffei, Archbishop and Cardinal (d. 1583)
December 1 – Takeda Shingen, Japanese warlord (d. 1573)
December 13 – Pope Sixtus V (d. 1590)
Anne Askew, English Protestant martyr (d. 1546)
John Aylmer, English divine (d. 1594)
Thomas Chaloner, English statesman and poet (d. 1565)
Philippe de Monte, Flemish composer (d. 1603)
Thomas Wyatt the Younger, English rebel (d. 1554)
Catherine Howard, Fifth Queen of Henry VIII of England, (born in between 1518 and 1524; d. 1542)
April 20 – Zhengde Emperor of China (b. 1491)
April 25 – Juan López de Padilla, Juan Bravo and Francisco Maldonado, executed Spanish rebels
April 27 – Ferdinand Magellan, Portuguese explorer (b. 1480)
May 10 – Sebastian Brant, German humanist and satirist (b. 1457)
May 17 – Edward Stafford, 3rd Duke of Buckingham (executed) (b. 1478)
June 15 – Tamás Bakócz, Hungarian Catholic cardinal and statesman (b. 1442)
June 21 – Leonardo Loredan, Doge of Venice (b. 1436)
July 24 – Juan Ponce de León, Spanish conquistador (b. 1460)
August 27 – Josquin des Prez, Flemish composer (b. c. 1450)
October 22 – Edward Poynings, Lord Deputy to King Henry VII of England (b. 1459)
December 1 – Pope Leo X (b. 1475)
December 13 – King Manuel I of Portugal (b. 1469)
1521 in art
Year 1521 (MDXXI) was a common year starting on Tuesday (link will display the full calendar) of the Julian calendar.