Santo Tomás was born in Seville, Spain. He arrived in Spanish colonial Viceroyalty of Peru in 1540, founding the convent and city of Yungay on 4 August 1540.
For the purpose of Indian Reductions, he learned the Quechua language dialect spoken along the Peruvian coast near Lima. The coastal dialect of Quechua was significantly different from that of Cuzco, which was described 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, the first book printed in the Quechua language. In the same year appeared his Lexicon, o Vocabulario de la lengua general del PERV.