Development of this area began about 1749 when Col. José de Escandón began bringing colonists to establish permanent settlements along Mexico's northern frontier. When parcels of land were granted to the colonists by the Spanish government in 1767, Ysabel Maria Sanchez, widow of early settler and rancher Joseph Lopez, was allotted more than 6,000 acres. The village of Lopeño that later developed on part of the land was named in honor of the Lopez family.
During the early 1800s, part of the Lopez land passed to the ownership of the Ramirez family, founders of the nearby village of Falcon. In 1821 Benito Ramirez built a combination home, fort, and chapel that later came to be called Fort Lopeño. Federal troops briefly occupied the fort during 1856 while in the area helping to ease border disturbances.
The general store established in Lopeño in the early 1900s by Serafin Benavides served as the area's only supply point at the time. A post office was established in 1920, and in 1934 oil and gas wells were successfully drilled just outside the village. When Falcon Reservoir was created in 1952, residents relocated their village to this site.