February 12, 1541 – Santiago, Chile is founded by Pedro de Valdivia.

April 7, 1541 – Francis Xavier leaves Lisbon on a mission to the Portuguese East Indies.

May 8, 1541 – Hernando de Soto reaches the Mississippi River and names it Río de Espíritu Santo.

June 26, 1541 – Francisco Pizarro is assassinated in Lima by the son of his former companion and later antagonist, Diego Almagro the younger. Almagro is later caught and executed.

August 23, 1541 – French explorer Jacques Cartier lands near Quebec City in his third voyage to Canada.

August 29, 1541 – The Ottoman Turks capture Buda, the capital of the Hungarian Kingdom.

September 11, 1541 – Santiago, Chile, is destroyed by indigenous warriors, led by Michimalonko.

September 13, 1541 – After three years of exile, John Calvin returns to Geneva to reform the church under a body of doctrine known as Calvinism.

December 10, 1541 – Thomas Culpeper and Francis Dereham are executed for having affairs with Catherine Howard, Queen of England and wife of Henry VIII.

January 26, 1541 – Florent Chrestien, French writer (d. 1596)

March 25, 1541 – Francesco I de' Medici, Grand Duke of Tuscany (d. 1587)

April 8, 1541 – Michele Mercati, Italian physician (d. 1593)