The Tataviam, also known as the Fernandeo, tribe of Indians and the Tongva had inhabited the valley for at least 6,000 years before the Spanish built the San Fernando Mission in 1797. The official first rancho and adobe settlement in the southeast part of the San Fernando Valley was occupied by the Reyes family, in what is now Encino, California. Another rancho settlement in the northeast part of the San Fernando Valley was occupied by the Cota Family, near the mission at San Fernando, California. The treaty ending the Mexican-American War in California was signed near the mouth of the Cahuenga Pass (at the southeast corner of San Fernando Valley) at an adobe owned by The Verdugo Family at Campo de Cahuenga in 1847.

The valley was a semi-desert and needed water in order to spur development and later urbanization. Once the aqueduct was built, crops such as corn, cotton, persimmons, lemons, oranges, and walnuts helped sustain the settlers and encouraged economic growth. Besides farming, the advent of three new industries – motion picture, automobile, and aircraft spurred urbanization. By 1960 the population in the valley had reached one million.

After the construction of the Owens Valley-Los Angeles Aqueduct, the mostly rural area was annexed by the city of Los Angeles in 1915, more than doubling the size of the city. A highly fictionalized story based on these events is told in the film Chinatown (1974). Los Angeles continued to consolidate its territories in the San Fernando Valley by annexing Laurel Canyon (1923), Lankershim (1923), Sunland (1926), La Tuna Canyon (1926), the incorporated city of Tujunga (1932), and Porter Ranch (1965). The additions expanded the Los Angeles portion of San Fernando Valley from the original 169 square miles (438 km2) to 224 square miles (580 km2) today. Six cities incorporated independent from Los Angeles: Glendale (1906), Burbank (1911), San Fernando (1911) Hidden Hills (1961), Calabasas (1991). Universal City is an unincorporated enclave that is home to Universal Studios theme park and Universal CityWalk.

The largest cities located entirely in the valley are Glendale and Burbank. The most populous districts of Los Angeles in the valley are North Hollywood and Van Nuys. Each of the two cities and the two districts named has more than 100,000 residents. Despite the San Fernando Valley’s reputation for sprawling, low-density development, the valley communities of Panorama City, North Hollywood, Van Nuys, Reseda, Canoga Park, and Northridge, all in Los Angeles, have numerous apartment complexes and contain some of the densest census tracts in Los Angeles. Poverty rates in the San Fernando Valley are lower than the rest of the county (15.3% compared to 17.9%). Nevertheless, in eight San Fernando Valley communities, at least one in five residents lives in poverty. The Pacoima district of Los Angeles is widely known in the region as a hub of suburban blight. Other San Fernando Valley communities, such as the Los Angeles sections of Mission Hills, Arleta, and Sylmar, have poverty rates well below the regional average. Many wealthy families live in the hills south of Ventura Boulevard, and along the hills to the north of the 118 freeway.

Communities in the San Fernando Valley are: Arleta, Cahuenga Pass, Canoga Park, Chatsworth, Colfax Meadows, Encino, Granada Hills, Kagel Canyon, Knollwood, Lake View Terrace, Lake Balboa, La Tuna Canyon, Mission Hills, NoHo Arts District, North Hills, North Hollywood, Northridge, Pacoima, Panorama City, Porter Ranch, Reseda, Shadow Hills, Sherman Oaks, Studio City, Sun Valley, Sunland, Sylmar, Tarzana, Toluca Lake, Toluca Woods, Tujunga, Valley Glen, Valley Village, Van Nuys,Ventura Business District, West Hills, West Toluca, Winnetka, Woodland Hills

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