|Covid-19|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: The Emperor of Ethiopia defeats an attack by the forces of Imam Ahmad Gragn.
May 8 – Spanish explorer Hernando de Soto reaches the Mississippi River, naming it the Rio de Espiritu Santo ("River of the Holy Spirit").
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 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.
October – An Algerian military campaign by Charles V of Spain (Habsburg) is unsuccessful.
The Portuguese defeat the Muslims near Lake Tana.
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.
January 24 – Magdalena Moons, Dutch heroine (d. 1613)
January 26 – Florent Chrestien, French writer (died 1596)
February 21 – Philipp V, Count of Hanau-Lichtenberg (d. 1599)
March 25 – Francesco I de' Medici, Grand Duke of Tuscany (died 1587)
April 8 – Michele Mercati, Italian physician and gardener (died 1593)
August 12 – Ipatii Potii, Metropolitan of Kiev (d. 1613)
Luigi Groto, Lutenist and poet (d. 1588)
Hernando de Cabezón, Spanish musician (died 1602)
September 16 – Walter Devereux, 1st Earl of Essex, English nobleman (died 1576)
September 17 – Roberto de' Nobili, Italian cardinal (d. 1559)
September 21 – Anna of Nassau-Dillenburg, Countess consort of Nassau-Weilburg (d. 1616)
November 9 – Menso Alting, Preacher and reformer (d. 1612)
November 25 – Michele Bonelli, Catholic cardinal (d. 1598)
December 12 – Johann Bauhin, Swiss botanist (d. 1613)
Pierre Charron, French philosopher (died 1603)
El Greco, or Domênikos Theotokópoulos (Greek: Δομήνικος Θεοτοκόπουλος), Cretian painter, sculptor and architect (died 1614)
Hatano Hideharu, Japanese samurai (died 1579)
Mizuno Tadashige, Japanese nobleman (died 1600)
Guðbrandur Þorláksson, mathematician (died 1627)
Hattori Hanzō, Ninja who served under Tokugawa Ieyasu (died 1596)
April – Jerzy Radziwiłł, Polish nobleman (born 1480)
May 27 – Margaret Pole, 8th Countess of Salisbury (executed) (born 1473)
June 26 – Francisco Pizarro, Spanish conquistador (born c. 1475)
July 4 – Pedro de Alvarado, Spanish conquistador (born 1495)
August – Juan de Valdés, Spanish religious writer (born 1500)
August 1 – Simon Grynaeus, German scholar and theologian (born 1493)
September 24 – Paracelsus, Swiss alchemist and physician (born 1493)
September – Beatriz de la Cueva, Governor of Guatemala (b. 1510)
October 18 – Margaret Tudor, queen of James IV of Scotland (born 1489)
November – Wolfgang Fabricius Capito, German reformer (born 1478)
November 30 – Amago Tsunehisa, Japanese warlord
December 10 – Thomas Culpeper, English courtier (executed)
December 24 – Andreas Karlstadt, Christian theologian and reformer (born 1486)
Jean Clouet, French miniature painter
Giovanni Guidiccioni, Italian poet (born 1480)
Year 1541 (MDXLI) was a common year starting on Saturday (link will display the full calendar) of the Julian calendar.