Lucas Vázquez de Ayllón (c. 1475, probably Castile, Spain – 18 October 1526) is a Spanish explorer who in 1526 establishes the short-lived San Miguel de Gualdape colony, the first European attempt at a settlement in what is now the continental United States.

Ayllón's account of the region inspires a number of later attempts by the Spanish and French governments to colonize the southeastern United States.