Born in the Mexican city of Zacatecas to Spanish colonists, he began his career as an Indian fighter in the frontier regions of northern Mexico. He married Isabel de Tolosa Cortés Moctezuma, a descendant of both Hernan Cortés, the conqueror of Mexico, and the Aztec Emperor Moctezuma (or Montezuma).
In 1595 he was ordered by Philip II to colonize the upper Rio Grande valley (explored by Francisco Coronado in 1540. His stated objective was to spread Roman Catholicism and establish new missions, however hopes of finding silver attracted most of his followers. He began the expedition in 1598, fording the Rio Grande at El Paso, Texas in May. That summer his party encamped among the Pueblo Indians of northern New Mexico.
Oņate soon gained a reputation as a stern ruler, to both his restless Spanish colonists who sought precious metals, and the indigenous people who suddenly found themselves under alien rule. His infamous suppression of the Acoma revolt, in which the left feet of the male captives were amputated by the Spaniards is still bitterly recalled.
In 1606, Oņate was recalled to Mexico City for a hearing into his conduct. After finishing plans for the foundation of Santa Fe he resigned his post, was tried, and eventually after delays, he was convicted of cruelty to both Indians and colonists, and adultery. He was banished from New Mexico, Oņate spent much of the rest of his life attempting to clear his name.
Eventually Oņate went to Spain, where the king gave him the position of mining inspector. He died in Spain in 1626.
Oņate is a controversial figure. Honored by some Anglo-Americans and Hispanics for his explorative ventures, he is still disdained by many Native Americans for his alleged cruelty to the Acoma Pueblo people. A twelve meter bronze equestrian statue of Oņate is currently being built by sculptor John Hauser for placement in downtown El Paso, Texas.