Hernando de Soto played an important role in Francisco Pizarro's conquest of the Inca Empire in Peru, but is best known for leading the first European expedition deep into the territory of the modern-day United States (through Florida, Georgia, Alabama, Mississippi, and most likely Arkansas). He is the first European documented as having crossed the Mississippi River.

De Soto's North American expedition was a vast undertaking. It ranged throughout what is now the southeastern United States, both searching for gold, which had been reported by various Native American tribes and earlier coastal explorers, and for a passage to China or the Pacific coast. De Soto died in 1542 on the banks of the Mississippi River; different sources disagree on the exact location, whether it was what is now Lake Village, Arkansas, or Ferriday, Louisiana.