Over 300 years ago, Ohlone Indians, also known as Costanoan, roamed the peninsula area catching fish and snaring small game in the verdant hills and valleys.  Oysters, clams, and mussels were abundant along the shoreline.  The Spanish soldiers arrived in 1769 and pillaged the territory, conquering the peaceful Ohlones, bringing much hardship and decimation to their tribe. After the Spaniards departed (and until California became a part of the United States) the Mexican government was in control.  The Mexican government gave huge land grants to its supporters. In 1835, Senor Don Jose Antonio Sanchez was granted the vast Rancho Buri Buri. Less than ten years later, Sanchez died, and his children retained 14,639 acres of their father's Northern Peninsula Land Grant.
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Heir, Astro Sanchez sold 1463.91 acres to Alfred Edmondson for $10,000 in 1853, and then Edmondson resold the same acreage to Charles Lux (1823-1887), an immigrant butcher, in 1856 for $18,000.  Lux used the land to graze and fatten cattle before herds were driven to San Francisco via El Camino Real.  It was on this property Lux built his family a beautiful country home and named the area Baden.  In 1858 Lux partnered with Henry Miller (1827-1916), another successful immigrant butcher, to buy land and sell beef during the California Gold Rush.  The two became wealthy land barons and later organized the Pacific Live Stock Company.  In 1890, after Lux's death, his heirs sold the land to Peter Iler of Omaha, who was representing meat packer Gustavus F. Swift. Swift selected the site as South San Francisco, a West Coast stockyard and market place, similar to his operations in South Omaha and South Chicago.

Needing money, Swift aligned with several Chicago capitalists and formed two joint stock corporations:  South San Francisco Land and Improvement Company, and the Western Meat Company.  The driving force behind the Land and Improvement Company was William J. Martin whose efforts to attract industries and workers to South San Francisco led to the city's growth and its incorporation on September 19, 1908.  Major industries continued to locate in South San Francisco and two world wars brought a transition to shipbuilding.  The Shaw-Batcher shipyard built cargo ships and between wars it built barges and dredges and fabicated pipe, becoming one of the pioneers of automatic welding machinery.  The shipyard in South San Francisco had four berths from which ships were launched sideways, two on each side of a large basin at Oyster Point.   Following World War II the population boomed and a well-balanced community of industrial and residential areas developed.

The 1950's brought modern industrial parks to the East of 101 area, such as Cabot, Cabot and Forbes; freight forwarding, light industries, and other airport related businesses thrived.  A new era for South San Francisco began in 1976 with the founding of Genentech by venture capitalist Robert Swanson and molecular biologist Dr. Herbert Boyer.  Their objective: to explore ways of using recombinant DNA technology to create breakthrough medicines.  This earned South San Francisco the title of "Birthplace of Biotechnology", and thus attracted other biotech and pharmaceutical businesses to the area, bringing economical growth and stability to the community for several years. In 2008, the city celebrated its centennial with many memorable events honoring its forefathers, and recognizing businesses, organizations, and outstanding citizens for their contributors.

History has proven that South San Francisco is resourceful; it evolves and transforms with the times...always ready for challenges and a new beginning.