Santo Tomás was born in Seville, Spain. He was educated in local church schools and entered the Dominican Order as a youth. After becoming ordained as a priest and serving in Spain for years, he was assigned as a missionary to the Spanish colonial Viceroyalty of Peru in 1540, soon after the initial conquest of 1533. He founded the convent (monastery) and city of Yungay on 4 August 1540 to evangelize to the Inca.
For the purpose of Indian Reductions, by which the Spanish brought natives together around missions for teaching and work, Domingo learned the Quechua language dialect spoken along the Peruvian coast near Lima. The coastal dialect of Quechua was significantly different from that current in Cuzco; these were described in detail by Diego González Holguín in the early 17th century.
In 1560 he published his Grammatica o arte de la lengua general de los indios de los Reynos del Perú in Valladolid, Spain. It was the first book to be printed in the Quechua language. In the same year he published his Lexicon, o Vocabulario de la lengua general del PERV.