In 1502 the newly appointed governor, Nicolás de Ovando, arrived in Hispaniola. The Spanish Crown expected Ovando to bring order to a colony in disarray. Ovando interpreted this as authorizing subjugation of the native Taínos. Thus, Ovando authorized the Jaragua Massacre in November 1503. In 1504, when Tainos overran a small Spanish garrison in Higüey on the island's eastern side, Ovando assigned Ponce de León to crush the rebellion. Ponce de León was actively involved in the Higüey massacre, about which friar Bartolomé de las Casas attempted to notify Spanish authorities. Ovando rewarded his victorious commander by appointing him frontier governor of the newly conquered province, then named Higüey also. Ponce de León received a substantial land grant which authorized sufficient Indian slave labor to farm his new estate.
Ponce de León prospered in this new role. He found a ready market for his farm produce and livestock at nearby Boca de Yuma where Spanish ships stocked supplies before the long voyage back to Spain. In 1505 Ovando authorized Ponce de León to establish a new town in Higüey, which he named Salvaleón. In 1508 King Ferdinand (Queen Isabella having opposed the exploitation of natives but dying in 1504) authorized Ponce de León to conquer the remaining Taínos and exploit them in gold mining.
His earlier exploration had confirmed the presence of gold and gave him a good understanding of the geography of the island. In 1508, Ferdinand II of Aragon gave permission to Ponce de León for the first official expedition to the island, which the Spanish then called San Juan Bautista. This expedition, consisting of about 50 men in one ship, left Hispaniola on July 12, 1508 and eventually anchored in San Juan Bay, near today's city of San Juan. Ponce de León searched inland until he found a suitable site about two miles from the bay. Here he erected a storehouse and a fortified house, creating the first settlement in Puerto Rico, Caparra. Although a few crops were planted, the settlers spent most of their time and Energy searching for gold. By early 1509 Ponce de León decided to return to Hispaniola. His expedition had collected a good quantity of the precious metal but was running low on food and supplies.
Even as Ponce de León was settling the island of San Juan, significant changes were taking place in the politics and government of the Spanish West Indies. On July 10, 1509, Diego Colón, the son of Christopher Columbus, arrived in Hispaniola as acting Viceroy, replacing Nicolás de Ovando. For several years Diego Colón had been waging a legal battle over his rights to inherit the titles and privileges granted to his father. The Crown regretted the sweeping powers that had been granted to Columbus and his heirs and sought to establish more direct control in the New World. In spite of the Crown's opposition, Colón prevailed in court and Ferdinand was required to appoint him Viceroy. Although the courts had ordered that Ponce de León should remain in office, Colón circumvented this directive on October 28, 1509 by appointing Juan Ceron chief justice and Miguel Diaz chief constable of the island, effectively overriding the authority of the governor. This situation prevailed until March 2, 1510, when Ferdinand issued orders reaffirming Ponce de León's position as governor. Ponce de León then had Ceron and Diaz arrested and sent back to Spain.
Rumors of undiscovered islands to the North West of Hispaniola had reached Spain by 1511, and Ferdinand was interested in forestalling further exploration and discovery by Colón. In an effort to reward Ponce de León for his services, Ferdinand urged him to seek these new lands outside the authority of Colón. Ponce de León readily agreed to a new venture, and in February 1512 a royal contract was dispatched outlining his rights and authorities to search for "the Islands of Benimy".
For the next several days the fleet crossed open water until April 2, 1513, when they sighted land which Ponce de León believed was another island. He named it La Florida in recognition of the verdant landscape and because it was the Easter season, which the Spaniards called Pascua Florida (Festival of Flowers). The following day they came ashore to seek information and take possession of this new land. The precise location of their landing on the Florida coast has been disputed for many years. Some historians believe it occurred at or near St. Augustine; others prefer a more southern landing at a small harbor now called Ponce de León Inlet; but some also believe that Ponce came ashore even farther south near the present location of Melbourne Beach, a theory that has been criticized by some scholars in recent years. The latitude coordinate recorded in the ship's log closest to the landing site, reported by Herrera (who had the original logbook) in 1601, was 30 degrees, 8 minutes. This sighting was recorded at noon the day before with either a quadrant or a mariner's astrolabe, and the expedition sailed north for the remainder of the day before anchoring for the night and rowing ashore the following morning. This latitude corresponds to a spot north of St. Augustine between what is now the Guana Tolomato Matanzas National Estuarine Research Reserve and Ponte Vedra Beach.
Ponce de León decided he should return to Spain and personally report the results of his recent expedition. He left Puerto Rico in April 1514 and was warmly received by Ferdinand when he arrived at court in Valladolid. There he was knighted, and given a personal coat of arms, becoming the first conquistador to receive these honors. He also visited Casa de Contratación in Seville, which was the central bureaucracy and clearinghouse for all of Spain's activities in the New World. The Casa took detailed notes of his discoveries and added them to the Padrón Real, a master map which served as the basis for official navigation charts provided to Spanish captains and pilots.
Three ships were purchased for his armada and after repairs and provisioning Ponce de León left Spain on May 14, 1515 with his little fleet. The record of his activities against the Caribs is vague. There was one engagement in Guadeloupe on his return to the area and possibly two or three other encounters. The campaign came to an abrupt end in 1516 when Ferdinand died. The king had been a strong supporter and Ponce de León felt it was imperative he return to Spain and defend his privileges and titles. He did receive assurances of support from Cardinal Francisco Jiménez de Cisneros, the regent appointed to govern Castile, but it was nearly two years before he was able to return home to Puerto Rico.
In early 1521, Ponce de León organized a colonizing expedition consisting of some 200 men, including Priests, farmers and artisans, 50 horses and other domestic animals, and farming implements carried on two ships. The expedition landed somewhere on the coast of southwest Florida, likely in the vicinity of Charlotte Harbor or the Caloosahatchee River. Before the settlement could be established, the colonists were attacked by a large party of native Calusa warriors. Ponce de León was mortally wounded in the skirmish when, historians believe, an arrow poisoned with the sap of the manchineel tree struck his thigh. The expedition immediately abandoned the colonization attempt and returned to Havana, Cuba, where Ponce de León soon died of his wounds. He was buried in Puerto Rico, in the crypt of San José Church from 1559 to 1836, when his remains were exhumed and transferred to the Cathedral of San Juan Bautista.
According to a popular legend, Ponce de León discovered Florida while searching for the Fountain of Youth. Though stories of vitality-restoring waters were known on both sides of the Atlantic long before Ponce de León, the story of his searching for them was not attached to him until after his death. In his Historia general y natural de las Indias of 1535, Gonzalo Fernández de Oviedo y Valdés wrote that Ponce de León was looking for the waters of Bimini to cure his aging. A similar account appears in Francisco López de Gómara's Historia general de las Indias of 1551. Then in 1575, Hernando de Escalante Fontaneda, a shipwreck survivor who had lived with the Native Americans of Florida for 17 years, published his memoir in which he locates the waters in Florida, and says that Ponce de León was supposed to have looked for them there. Though Fontaneda doubted that Ponce de León had really gone to Florida looking for the waters, the account was included in the Historia general de los hechos de los castellanos of Antonio de Herrera y Tordesillas of 1615. Most historians hold that the search for gold and the expansion of the Spanish Empire were far more imperative than any potential search for such a fountain.
There is a possibility that the Fountain of Youth was an allegory for the Bahamian love vine, which locals brew today as an aphrodisiac. Ponce de León could have been seeking it as a potential entrepreneurial venture. Woodrow Wilson believed Indian servants brewing a "brown tea" in Puerto Rico may have inspired Ponce de León's search for the Fountain of Youth. Arne Molander has speculated that the adventurous conquistador mistook the natives' "vid" (vine) for "vida" (life) – transforming their "fountain vine" into an imagined "fountain of life".