Lucas Vasquez De Ayllon (c. 1475-1526), Spanish adventurer and colonizer in America, was born probably in Toledo, Spain, about 1475. He accompanied Nicolas Ovando to Hispaniola (Santo Domingo) in 1502, and there became a magistrate of La Concepcion and other towns, and a member of the superior court of Hispaniola. He engaged with great profit in various commercial enterprises, became interested in a plan for the extension of the Spanish settlements to the North American mainland, and in 1521 sent Francisco Gordillo on an exploring expedition which touched on the coast of the Florida peninsula and coasted for some distance northward. Gordillo's report of the region was so favourable that Ayllon in 1523 obtained from Charles V. a rather indefinite charter giving him the right to plant colonies. He sent another reconnoitring expedition in 1525, and early in 1526 he himself set out with 500 colonists and about 100 African slaves. He touched at several places along the coast, at one time stopping long enough to replace a wrecked ship with a new one, this being considered the first instance of shipbuilding on the North American continent.

Sailing northward to about latitude 33° 40′, he began the construction of a town which he called San Miguel. The exact location of this town is in dispute, some writers holding that it was on the exact spot upon which Jamestown, Va., was later built; more probably, however, as Lowery contends, it was near the mouth of the Pedee river. The employment of negro slaves here was undoubtedly the first instance of the sort in what later became the United States. The spot was unhealthy and fever carried off many of the colonists, including Ayllon himself, who died on the 18th of October 1526. After the death of their leader dissensions broke out among the colonists, some of the slaves rebelled and escaped into the forest, and in December the town was abandoned and the remnant of the colonists embarked for Hispaniola, less than 150 arriving in safety.

See Woodbury Lowery, Spanish Settlements within the Present Limits of the United States (2 vols., New York, 1903-1905).