Western Honduras was at the southeastern edge of the great Maya civilization during the 1st millennium ad, and the ruins at Copán attest to the advanced stage of the country’s population. The Maya, however, were already in decline by the time Christopher Columbus reached their shores on his fourth voyage in 1502. Several non-Maya tribes also inhabited the Caribbean coastal region. The indigenous population was decimated by the Spanish conquest and by the European diseases it introduced, but the number of Spanish settlers was small and included few women. Race mixture followed rapidly therefore, and mestizos became Honduras’s dominant ethnic group.

When the Spanish arrived to colonize Honduras, the land was occupied by a variety of indigenous peoples, the most advanced of whom were the Maya. Gold stimulated Spanish conquest of the area early in the 16th century, and the Honduran gold-mining town of Gracias became the capital of Spanish Central America (the Audiencia de los Confines) in 1544. By 1548, however, the Spaniards had exhausted the gold, and Santiago (Antigua Guatemala) became the new capital of the Kingdom of Guatemala. Honduras, with its capital at Comayagua and agriculture the base of its economy, was a province of that kingdom (audiencia) within the Viceroyalty of New Spain. In the 1570s, a silver strike in the highlands brought a rush of prospectors to Honduras, resulting in the rise of an important population centre at Tegucigalpa, which competed thereafter, especially in the 18th century, with Comayagua.

The conquest of Honduras began in 1524 and was characterized by bitter struggles among rivals representing Spanish power centers in Mexico, Panama, and Hispaniola. Hernán Cortés, the conqueror of Mexico, went to Honduras in 1525 to establish a firm claim, but the discovery of gold there made it a center of intrigue and conflict for several years. Pedro de Alvarado, the governor of the Kingdom of Guatemala, finally overcame all challengers in 1539 to gain control of Honduras. The province became a part of the Guatemalan kingdom, which encompassed almost all of Central America and was itself a part of the vast Spanish colony known as the Viceroyalty of New Spain. Comayagua, established in 1540, served as the province’s capital during most of the colonial period. An early mining boom around Gracias gave the town such importance that in 1544 it became the capital for the Kingdom of Guatemala. The gold and silver deposits were more limited than originally believed, however, and Honduras lost its early importance; the regional capital was moved to Santiago de Guatemala (today known as Antigua Guatemala) in 1549.