- Apr 20 Zhengde, 10th Emperor of the Ming Dynasty, dies at 29
- Apr 22 Juan de Padilla, Spanish nobleman/communero-rebel, beheaded
Ferdinand Magellan
Apr 27 Ferdinand Magellan, Portuguese explorer, killed by Filipino natives at 50 while on voyage to circumnavigate the world

Ferdinand Magellan
Juan Ponce de León
Jul 15 Juan Ponce de León, Spanish explorer and conquistador who searched for the fountain of youth and the first European to discover Florida, dies at 61

Juan Ponce de León
- Dec 13 Manuel I, King of Portugal (1495-1521) during era of Portuguese exploration known as "Manuel The Fortunate", dies at 52