1581

January–March

• January 11 - Chandrasen Rathore, ruler of the Kingdom of Marwar dies at the age of 39, leaving a power vacuum that allows the Mughal Empire to take control of the kingdom.
• January 14 - The Treaty of Drohiczyn is concluded, ending the Livonian War and adding the conquered city of Riga to the Polish-Lithuanian Commonwealth.
• January 23 - The Treaty of Plessis-les-Tours between the Duchy of Anjou and most of the states of the Dutch Republic is ratified at Bourdeaux, granting François, Duke of Anjou executive authority over the Republic with the title "Protector of the Liberty of the Netherlands".
• February 8 - Prince Shin Thissa, later to become King of Burma in 1599 as Nyaungyan Min, receives his first executive job when he is appointed to be Governor of Nyaungyan by his father, King Bayinnaung.
• February 23 - The Spanish Army is forced to abandon the siege of Steenwijk in the Netherlands after more than four months.
• March 18 - The Parliament of England's Act against Reconciliation to Rome imposes heavy fines, for practising Roman Catholicism.
• March 25 - Iberian Union: Philip II of Spain is crowned Philip I of Portugal.

April–June

• April 4 - Following his circumnavigation of the world, Francis Drake is knighted by Elizabeth I of England.
• May 15 - Zsigmond Báthory, the 8-year-old son of Kristóf Báthory, ruler of the Principality of Transylvania, is elected by the Diet of Transylvania as the new voivode at the request of Kristóf, who dies 12 days later.
• May 26 - In Burma, Thiri Thudhamma Yaza of Martaban becomes the new Viceroy of Martaban after the demise of Minye Nandameit.
• June 2 - James Douglas, 4th Earl of Morton, the last regent for Scotland from 1572 to 1578 during the minority of King James VI, is beheaded at Edinburgh using the "Scottish Maiden", after being convicted of conspiracy in the 1567 murder of Henry Stuart, Lord Darnley, consort of Mary, Queen of Scots and father of King James."
• June 14 - The representatives of the States General of the Netherlands vote to declare that the throne of the Union of Utrecht is vacant because of the erratic behavior of King Philip II.

July–September

• July 11 - The Knights Hospitaller depose Jean de la Cassière as Grandmaster and appoint Mathurin Romegas in his place.
• July 14 - English Jesuit Edmund Campion is arrested.
• July 22 - At a meeting of the States General of the Union of Utrecht at Antwerp, the representatives vote to proclaim their independence from Spain in the Act of Abjuration, abjuring loyalty to Philip II of Spain as their sovereign, and appointing Francois, Duke of Anjou, as the new sovereign of the Netherlands; public practice of Roman Catholicism is forbidden.
• July 26
• *The Act of Abjuration is signed at The Hague by representatives of eight Dutch provinces as a declaration of independence from Spanish rule and a secession from the Union of Utrecht. The signing confirms a decision made in a July 22 meeting of the States General in Antwerp. King Philip II of Spain refuses to acknowledge the Abjuration.
• *A meteorite strikes the Earth in Thuringia in the Holy Roman Empire.
• July 27 - Capture of Breda: After a surprise attack the day before, Spanish troops under the command of Claude de Berlaymont, Lord of Haultepenne, take the walled city Breda in the Netherlands. Once inside the gates, the Spanish troops overcome the defenders and carry out the massacre of 584 citizens in the "Haultepenne Fury".
• August 28 - The army of King Stephen Báthory of Poland begins its siege of the Russian garrison of Pskov.
• September 6 - A mercenary army of Sweden, under Pontus De la Gardie, captures Narva from Russia.
• September 23 - Martín Enríquez de Almanza arrives in Lima and becomes the new Viceroy of Peru, replacing Francisco de Toledo, who was summoned home by King Philip II.
• September 30 - In Japan, warlord Oda Nobunaga invades the Iga Province. With 42,000 troops under his command against 10,000 defenders led by Takino Jurobei, Nobunaga controls most of central Japan within eight days.

October–December

• October 8 - The Tenshō Iga War ends in Japan with the surrender of Kashiwara Castle to Oda Nobunaga.
• October 10 - King Bayinnaung of Burma, who created the largest empire in mainland southeast Asia, dies at age 65.
• October 15 - Ballet Comique de la Reine, the first narrative ballet, devised by Louise of Lorraine, wife of Henry III of France, and choreographed by Balthasar de Beaujoyeulx, opens in its first performance at the court of Catherine de' Medici, in the Louvre Palace in Paris, as part of the wedding celebrations for Marguerite of Lorraine.
• November 4 - Jean de la Cassière is restored as Grandmaster of the Knights Hospitaller, by Pope Gregory XIII.
• December 1 - In England, Jesuit priest Edmund Campion is executed for treason.

Date unknown

• The Ming Dynasty Chancellor of China, Chief Grand Secretary Zhang Juzheng, imposes the Single Whip Reform, by which taxes are assessed on properties recorded in the land census, and paid in silver, as the accepted medium of exchange.
• The Trier witch trials begin.
• John Dee practices angel magic with Barnabas Saul, but with no success.
• Guru Arjan Dev becomes the fifth Guru of Sikhs, succeeding his father Guru Ram Das.
• The last Bishop of Meissen, John IX of Haugwitz, resigns his office in the wake of the Reformation.