A list of events in the 1500s, otherwise known as the Sixteenth Century, related to Pirates of the Caribbean.
- Unknown date – Hernán Cortés conquered Mexico and the Aztec Empire. Note: In real-world history, Cortés conquered the Aztecs with only his armies. But according to the Jack Sparrow series, Cortés did this through the use of his cursed sword.
- June 29 – Montecuhzoma was killed in some battle following Hernán Cortés' return in Tenochtitlan, Mexico.
- Unknown date – Sent to discover the marvels of the New World, the Santiago disappeared on the route taken during Ponce de León's search for the Fountain of Youth. Ponce de León died at some point on the wreck of his ship. Note: In real-world history, Ponce de León died on Cuba in 1521 because of a wound from a poisoned arrow. But according to promotional material for Pirates of the Caribbean: On Stranger Tides, Ponce de León died aboard the Santiago at some point during his search for the Fountain.
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