The area which is now South San Francisco was originally part of Rancho Buri Buri, a large Mexican land grant to the Sanchez family dating to 1827.
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Swift proposed the name South San Francisco based on South Chicago and South Omaha, where the Swift company already had plants. Iler of Omaha, Nebraska, an agent of the Beef Trust, purchased Lux's property, and in 1891 ownership was transferred to the South San Francisco Land and Improvement Company.
The area was divided into industrial and residential districts, and the company installed lighting, sewer connections, and water distributions in the residential areas.
It has tripled since World War II with the opening of such subdivisions as Buri Buri, Winston Manor and Westborough on the slopes west of El Camino; The city is particularly noted for the South San Francisco hillside sign on Sign Hill, which rises to the north of the city, with large white letters that proclaim "South San Francisco, The Industrial City".
The sign, a tribute to the city's industrial past, is listed on the National Register of Historic Places.
The major manufacturers closed, and new development was focused on office parks, housing, high-rise hotels, and yacht harbors.