Hernando de Soto was born in Jerez de los Caballeros, Spain sometime around the year 1500. He was born to parents who lived in Extremadura, an area of great hardship and poverty. Like many young men at the time, de Soto longed to escape Extremadura and achieve military fame exploring new lands.

In 1514, de Soto sailed with the Spanish governor of Panama where he assisted in the conquest of Central America. From an early age, de Soto gained a reputation for bravery, intellect, and brutality. In 1528, de Soto became regidor or Guatemala and sailed from there to the Yucatan Peninsula of Mexico, hoping to find a passage from the Atlantic to Pacific Ocean that would enable Spanish trade with the East Indies. The expedition ultimately failed, and de Soto joined Francisco Pizzaro and his conquest of South America. Because de Soto had a major part in the conquest of the Incan Empire, he became fabulously wealthy upon his return to Spain. De Soto was made governor of Cuba, and was expected to colonize the mainland of North America. He chose 620 men for the voyage from Cuba to the interior of North America. De Soto hoped to find the passage from the Atlantic Ocean to the Pacific Ocean.

In May of 1539, de de Soto, 620 men, and 220 horses land at Charlotte Harbor, Florida. He named it Espíritu Santo after the Holy Spirit. The expedition then traveled north through the peninsula of Florida where they endured native ambushes along the way. By 1540, de Soto had reached Georgia and South Carolina, in pursuit of gold mines rumored to exist in the region. Unsuccessful in his attempts to find gold, de Soto continued north into the Appalachians of North Carolina. Once again, there was no gold to be found, but de Soto spent a month in the mountains resting his horses before traveling to Tennessee and then south again toward the Gulf of Mexico to meet supply ships. While traveling south, de Soto and his men were ambushed by the Choctaw Indians near their fortified city of Mabila. In the battle, 20 of de Soto's men were killed and thousands of Indians died. Despite the victory, de Soto and his men lost most of their possession and many had become sick. Consequently, de Soto directed his expedition back north into Tennessee where they spent the winter.

After the winter, de Soto's expedition traveled south west. On May 8, 1541, Hernando de Soto discovered the Mississippi River, although de Soto was not exactly thrilled with the finding. The Mississippi River was a huge, broad river that stood in the way of his expedition. It took over a month to build the appropriate floats to navigate across the river. Once across the river, the expedition continued into Arkansas, Oklahoma, and Texas. They spent the next winter on the Arkansas River. Things began falling apart for de Soto, when Juan Ortiz, his faithful interpreter died. The death of Ortiz made the communication with Indians and the procurement of food much harder. Furthermore, while in Arkansas, de Soto and his men clashed with the Tula Indians which took a great toll on the already weakened men. On May 21, 1542, Hernando de Soto himself died of a fever.

At the time, the de Soto expedition was seen as a great failure. De Soto failed to establish any permanent colonies, found no gold, and did not find the passage between the two great oceans. Furthermore, his expedition left death and disease wherever it traveled that resulted in the destruction of countless Indian villages. De Soto's expedition, however, did provide the first documented descriptions of the Indians in the southeastern United States and caused the Spanish to concentrate their colonies in Florida and along the Pacific coast.