- Jan 10 Gerardus Noviomagus [Gerrit Geldenhauer], Dutch theologist, die at 59
- Feb 1 Girolamo Aleandro, Italian Catholic cardinal, dies at 61
- Feb 13 Catherine Howard, Queen of England (1540-42), 5th wife of Henry VIII, beheaded at 18 or 19 for adultery
- Feb 13 Jane Boleyn, Viscountess Rochford, sister-in-law of King Henry VIII of England, beheaded in the Tower of London at 36 or 37
Hernando de Soto (c. 1500-1542)
May 21 Spanish conquistador and 1st European to discover the Mississippi River, dies of a fever while searching for gold, near the Mississippi River at about 46
- Jun 19 Leo Jud[ae], Swiss pastor/church reformer
- Aug 24 Gasparo Contarini, Italian diplomat and cardinal (b. 1483)
- Aug 29 Cristovão da Gama, Portuguese soldier (born c. 1516)
- Sep 16 Diego de Almagro, Spanish captain-general of Peru, beheaded
- Sep 21 Juan Boscán Almogáver, Spanish poet
- Oct 6 Thomas Wyatt, English poet (b. 1503)
- Oct 27 Abraham ben Avigdor, rabbi/author (commentary on Tur), dies
James V (1512-1542)
Dec 14 King of Scotland (1513-42), dies likely of cholera or dysentery at 30
- Dec 28 Albert Pigge [Pighius], Dutch theologist/astronomer, dies at about 52