The boundaries of the Mission Historic District were designed primarily to include the lower four missions in the San Antonio area (Listed from north to south: Concepcion, San Jose, San Juan Capistrano, and Espada), their acequias and fields, and secondarily the significant preserved historic and prehistoric sites in the area. These boundaries represent an area less impacted than most areas of San Antonio by urban development.
The area designated as the Mission Historic District, located along the San Antonio River in the south section of the city, originally attracted both prehistoric Indian and historic Spanish and Anglo populations because of the prevalence of unique natural resources. The abundant water, game, and other natural foods seem to have provided prehistoric Indians with an ample non-agricultural subsistence type of lifestyle based upon hunting, gathering, and fishing. The arrival of the Spanish missionaries brought primarily agricultural exploitation of this area by means of the acequia systems. After the establishment of the Spanish Missions, the area was similarly utilized for agricultural purposes as well as local industries; this trend continued well into the twentieth century.
The growth and expansion of the City of San Antonio, primarily since the 1930s, has transformed much of this area into an urban or suburban environment. The southern portion of this area, roughly between Mission San Juan and Mission Espada, can be characterized as an open-space, rural environment, with some agriculture still being practiced through use of the San Juan and Espada acequias. The remaining historic district area is interspersed with public and institutional land uses among residential, industrial, commercial, and historic areas through which the San Antonio River passes.