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Year 1581 (MDLXXXI) was a common year starting on Sunday (link will display the full calendar) of the Julian calendar, and a common year starting on Thursday (link will display full calendar) of the Proleptic Gregorian calendar.
- July 14 English Jesuit Edmund Campion is arrested.
- July 26
- August 28 – The army of King Stephen Báthory of Poland begins its siege of the Russian garrison of Pskov
- Summer (probable) – Yermak begins the Russian conquest of the Khanate of Sibir, with a band of 1,636 men.
- September – A mercenary army of Sweden, under Pontus De la Gardie, captures Narva from Russia.
- 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 – Execution in England of the Jesuit priest Edmund Campion for treason.
- The Knights Hospitaller depose Jean de la Cassière as Grandmaster, and appoint Mathurin Romegas.
- 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.
- Oda Nobunaga invades the Iga Province.
- 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.