On January 3, 1521, Pope Leo X issues the papal bull Decet Romanum Pontificem, which excommunicates Martin Luther from the Catholic Church.

Martin Luther, the chief catalyst of Protestantism, defies the Holy Roman Emperor Charles V by refusing to recant his writings. He had been called to Worms, Germany, to appear before the Diet (assembly) of the Holy Roman Empire and answer charges of heresy. His response, known as the "Here I Stand" speech, would go down as one of the greatest pieces of oratory in world history.

After traveling three-quarters of the way around the globe, Portuguese navigator Ferdinand Magellan is killed during a tribal skirmish on Mactan Island in the Philippines. Earlier in the month, his ships had dropped anchor at the Philippine island of Cebu, and Magellan met with the local chief, who after converting to Christianity persuaded the Europeans to assist him in conquering a rival tribe on the neighboring island of Mactan. In the subsequent fighting, Magellan was hit by a poisoned arrow and left to die by his retreating comrades.

After a three-month siege, Spanish forces under Hernán Cortés capture Tenochtitlán, the capital of the Aztec empire. Cortés’ men leveled the city and captured Cuauhtémoc, the Aztec emperor.