1541

January–June

• February 12 - Pedro de Valdivia founds Santiago del Nuevo Extremo, which will become the capital of Chile.
• April 7 - Francis Xavier leaves Lisbon, on a mission to the Portuguese East Indies.
• April 24 - Battle of Sahart: Gelawdewos is defeated by the forces of Imam Ahmad ibn Ibrahim al-Ghazi.
• May 8 - Spanish explorer Hernando de Soto reaches the Mississippi River, naming it the Rio de Espiritu Santo.
• May 23 - Jacques Cartier departs from Saint-Malo, France on his third voyage.
• June 18 - By the Crown of Ireland Act, the Parliament of Ireland declares King Henry VIII of England and his heirs to be Kings of Ireland, replacing the Lordship of Ireland with the Kingdom of Ireland.

  July–December

• July 9 - Estêvão da Gama departs Massawa, leaving behind 400 matchlock men and 150 slaves under his brother Cristóvão da Gama, with orders to assist the Emperor of Ethiopia to defeat Ahmad ibn Ibrahim al-Ghazi, who has invaded his Empire.
• August 29 - The Janissaries of Suleiman the Magnificent take Buda by ruse, hiding themselves as visitors.
• September 9-11 - Spanish noblewoman Beatriz de la Cueva serves as governor of the colony of Guatemala, before she is killed in a mudslide from Volcán de Agua, which ruins the capital city, Ciudad Vieja.
• September 13 - After three years of exile, John Calvin returns to Geneva to reform the church under a body of doctrine that comes to be known as Calvinism.
• October - An Algerian military campaign by Charles V of Spain is unsuccessful.
• December 10 - Thomas Culpeper and Francis Dereham are executed for having affairs with Catherine Howard, Queen of England and wife of Henry VIII.

  Date unknown

• Ottoman Sultan Suleiman the Magnificent seals off The Golden Gate in Jerusalem.
• Iceland adopts the Lutheran faith.
• Gerardus Mercator makes his first globe.
• The first official translation of the entire Bible into Swedish is made.
• John Calvin translates his Institutio Christianae religionis into French, as L'Institution chrétienne.
• Elia Levita's chivalric romance, the Bovo-Bukh, is first printed, the earliest published secular work in Yiddish.