Old Ramireno was located on land granted to Don Jose Luis Ramirez by the King of Spain in 1784. Part of the colonization effort of Col. Jose de Escandon, Ramirez' grant was designated as Porcion 5. A resident of Revilla (now Guerrero), Nuevo Santander (now Tamaulipas) in Mexico, Don Jose Luis Ramirez, his wife Maria Bacilia Martinez, and their children moved across the Rio Grande and established a home on their land in present Zapata County. Don Jose Luis and Maria Bacilia Martinez had ten children. Their families and descendants formed the nucleus of the community of Ramireno.
The men of the ill-fated Mier Expedition of 1842 camped at Ramireno during their march to Mexico, and the settlement was also the site of United States military activity during the Mexican Revolution and border raids of 1916-17.
The construction of Falcon Reservoir on the Rio Grande caused the relocation of several area communities, including Ramireno. The settlement founded by Don Jose Luis Ramirez was moved in 1953 to a site two miles from the original Ramirez Ranch. The hand-cut sandstone Ramirez ranch home was covered by the waters of Falcon Reservoir.