Misión Santa Rosa de las Palmas, also known as Todos Santos Mission, was founded by the Roman Catholic Jesuits in 1733. After 1748, the mission was known as Nuestra Señora del Pilar de la Paz. The mission was the first European settlement at the site of what is now the city of Todos Santos, Baja California Sur. The Santa Rosa Mission was located in one of the few areas of Baja California suitable for agriculture. The residents of the Mission were primarily Guaycura Native Americans (American Indians) whom the Jesuits and their successors, the Franciscans and Dominicans, attempted to convert to Christianity and to make into sedentary farm workers. Recurrent epidemics of introduced European diseases reduced the Indian population to only a handful by the 19th century and in 1825 the mission was closed.
In 1724, Jesuit priest Jaime Bravo, stationed at the Misión de Nuestra Señora del Pilar de La Paz Airapí at present day La Paz, Baja California Sur, founded a visita (subsidiary post to a mission) at a place he named Todos Santos which was near the Pacific Ocean. In the deserts of Baja California Todos Santos was attractive because of a relative abundance of water, tillable land, and good grazing for livestock. The site was inhabited by Uchiti Indians, probably a band of the Guaycura people. The visita became the mission of Santa Rosa in 1733 under Sigismundo Taraval.
Agriculture at Santa Rosa was successful, but the area was contested between warring bands of the Guaycura, including the Uchiti, and Pericues peoples. The Uchiti, in particular, were hostile to the mission and its Christian converts (neophytes). About 10 Spanish and a few dozen neophyte soldiers attempted to protect Santa Rosa, other missions in southern Baja California, the Jesuits, and the neophytes. In addition, the Indians living at or near the mission were impacted by recurrent epidemics of European diseases such as smallpox and measles. Syphilis, although known in America before the Europeans, was also a serious disease and may have been spread widely in Baja California by visiting or castaway Spanish and English sailors.