| 21 May 1067 | Byzantine Empire [administration] | The Byzantine emperor Constantine X dies. He is succeeded by his widow Eudocia Macrembolitissa. |
| 21 May 1254 | Holy Roman Empire, Germany, Sicily [political events] | The death of Conrad IV, Holy Roman Emperor and king of Sicily and Jerusalem, while on his way to recover control in Germany leads to an intensification of the factious dispute over succession within the royal house. He is succeeded in Sicily by his son, Conrad V (Conradin). |
| 21 May 1268 | Mameluke Sultanate, Syria, Principality of Antioch [wars] | The Mameluke sultan of Egypt, Baybars, takes Antioch, Syria (modern Antakya, Turkey), from its Crusader occupants, and destroys the city with unprecedented slaughter. The city never recovers. |
| 21 May 1369 | France, England [Hundred Years War (1337–1453)] | King Charles V of France declares war on England. |
| 21 May 1377 | Germany, Holy Roman Empire [revolution] | Ulm and thirteen other German towns that are members of the Swabian League defeat the forces sent by the Holy Roman Emperor Charles IV to suppress their organization, at Reutlingen, Germany. |
| 21 May 1471 | England [Wars of the Roses (1455–85)] | Richard, duke of Gloucester, brother of King Edward IV of England, defeats an attack on London, England, by the Lancastrian Lord Fauconberg that is aimed at taking Henry VI from confinement in the Tower of London. Edward has Henry executed, thereby extinguishing the Lancastrian dynasty. |
| 21 May 1471 | Germany [births and deaths] | Albrecht Dürer, considered to be the greatest German painter and printmaker of the Renaissance, born in Nuremberg, Germany (–1528). |
| 21 May 1506 | Spain, Genoa [births and deaths] | Christopher Columbus, Italian navigator and explorer, the first explorer of the New World to achieve long-term historical impact, dies in Valladolid, Spain (54). |
| 21 May 1527 | Spain, Portugal [births and deaths] | Philip II, King of Spain 1556–98, and King of Portugal 1580–98, who brought Spain to the zenith of its power, born in Valladolid, Spain (–1598). |
| 21 May 1542 | Spain, North America [exploration] | After the death of Hernando de Soto, leader of the Spanish expedition to southeastern North America, the remnants of his expedition return to New Spain (Mexico) by raft the following year. With the failure of Francisco Vázquez de Coronado's western expedition, this deters the Spanish from further exploration north of the Caribbean. |
| 21 May 1553 | England [political events] | The young king Edward VI of England, dying of tuberculosis, bestows the succession on his fellow Protestant, Lady Jane Grey, at the urging of her father-in-law John Dudley, Duke of Northumberland; the hereditary candidate, Mary Tudor, is Catholic. Dudley then marries his son Lord Guildford Dudley to Lady Jane Grey, the 15-year-old daughter of Henry, Duke of Suffolk, and great-niece of the late king Henry VIII of England; through placing them on the throne, he hopes to retain control of the kingdom. |
| 21 May 1662 | UK, Portugal [political events] | King Charles II of England marries Catherine of Braganza, daughter of King John IV of Portugal, at Portsmouth, England. |
| 21 May 1674 | Poland [administration] | Following his victory over the Ottoman Turks at Chocim, John Sobieski is elected king of Poland as John III. |
| 21 May 1688 | England [births and deaths] | Alexander Pope, English poet and satirist, author of ‘Essay on Man’, born in London, England (–1744). |
| 21 May 1849 | Germany [political events] | The core of the deputies to the German National Assembly in Frankfurt withdraw, having been unable to organize a peaceful parliamentary union of the German states. |
| 21–28 May 1871 | France [political events] | In ‘Bloody Week’ in Paris, France, fighting between government troops and demonstrators ends in the defeat of the extreme left-wing Paris Commune (provisional national government) at a cost of 20,000–30,000 lives. |
| 21 May 1904 | France [football] | The Fédération Internationale de Football Association (FIFA), a world governing body for football, is founded in France, without British support. |
| 21 May 1916 | United Kingdom [natural resources] | The British government introduces British Summer Time. The clocks are put forward one hour to help save valuable resources such as coal during wartime. |
| 21 May 1921 | [births and deaths] | Andrey Dimitriyevich Sakharov, Soviet nuclear physicist and outspoken supporter of human rights and civil liberties, born in Moscow, Russia (–1989). |
| 21 May 1996 | UK, Europe [political events] | Britain begins a policy of noncooperation with its European partners in response to the European Union (EU) ban on British beef exports, disrupting the running of the EU and the Intergovermental Conference to plan the future development of Europe. |
| 21 May 2003 | Algeria [natural disasters] | A major earthquake measuring 6.7 on the Richter scale in northern Algeria kills at least 2,200 people and injures thousands more. |
