Santa Susana is a former railroad town located mostly within the City of Simi Valley and partly in the neighboring Los Angeles neighborhood of Chatsworth. A small portion of the community, outside the Simi Valley city limits to the south of the Ventura County Metrolink rail line, is an unincorporated area and census-designated place (CDP). The community is in the eastern part of the Simi Valley and on the western part of Chatsworth, Los Angeles, surrounding the Santa Susana Mountains. With 87.2% identifying as being Caucasian in the 2010 U.S. Census, the Santa Susana CDP has the fifth highest percentage of white residents in Los Angeles County.

The town by the Santa Susana Mountains in the Simi Valley was founded in 1903, shortly after the Southern Pacific Company built the Santa Susana Depot. It is also spelled Santa Susanna, while it is currently more commonly referred to as the Santa Susana Knolls, which is the officially designated name, or the Simi Knolls. The name of Santa Susana is now more generally applied to a larger area at the very east end of the Simi Valley (often called east of East Simi Valley) in easternmost Ventura County, which was the name of the early settlement located at Tapo Street and East Los Angeles Avenue that is now within the city limits. The historic Santa Susana Depot was located there before being moved farther east along the coast route railroad and made into a museum. The Simi Valley train station opened in 1993 about midway between the historic site and the museum location next to Santa Susana Knolls. The 2010 United States census reported the Santa Susana CDP's population as 1,037. It is a sparsely populated rural area with rustic housing and no set-houses, in a hilly and relatively forested part of the valley.

The area was inhabited by the Chumash Indians as early as 500 AD and there have been numerous Chumash artifacts found in the area, in addition to the pictographs in Burro Flats Painted Cave. In the 1920s, the Knolls became home to brothels and also a religious cult. During the late 1960s Charles Manson and the Manson Family partially lived at Spahn's Movie Ranch.[14] During the 1950s and '60s, the Corriganville Movie Ranch and other areas was utilized as movie sets for Western movies. Films and TV-series filmed here includes Gunsmoke, Bonanza, The Lone Ranger, Adventures of Superman, The Adventures of Robin Hood (1938), The Three Musketeers, Tales of the Texas Rangers, Billy the Kid Versus Dracula, Fort Apache, Star Trek, Wagon Train, and hundreds of other mostly Western-inspired movies and TV-shows.

The rural Santa Susana is home to numerous species of native wildlife, including large amounts of snakes, coyotes, hawks and mountain lions.

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