Santo Domingo is one of the largest most conservative Indian Pueblos in New Mexico. When Don Juan de Onate visited Santo Domingo in 1598, the pueblo was on the north bank of the Galisteo Creek, few miles east of the present village. Galisteo floodwaters washed this village away shortly afterwards and the survivors established a new Pueblo on the Rio Grande. Flood waters struck Santo Domingo in 1692 and again in 1886, washing away much of the Pueblo each time. Most of the present pueblo and the present mission church were built since the disastrous flood of 1886. During much of the Spanish colonial period, Santo Domingo was an important Franciscan mission center and the ecclesiastical capital of New Mexico. A mission church erected here before 1607 by Fray Juan de Escalona, was considered one of the largest and finest in New Mexico. It was washed away in the 1886 flood, but most of the records and religious objects were saved.
Santo Domingo played host to many famous visitors during its long history, including Zebulon Pike in 1809 and General Stephan Watts Keamy in1846.
In 1598, Santo Domingo Tribe was designated as the Capitol for the 19 Pueblo Indian Tribes in the State of New Mexico. The inhabitants of Santo Domingo Pueblo today are conservative and traditional. Their ceremonial dances are considered among the finest to be seen in New Mexico.