[11] Lux bought out Edmonson's interest in 1856 and founded the town of Baden (now a neighborhood of South San Francisco) near the 12-Mile House.

[12] The city of South San Francisco was conceived as an industrial suburb and was promoted by representatives of the Beef Trust, a group including some of the country's largest meat packing firms.

In 1890 Peter E. Iler of Omaha, Nebraska, an agent of the Beef Trust, purchased the Lux properties; ownership was transferred to the South San Francisco Land and Improvement Company in 1891.

During the Great Depression the city maintained 35 industrial operations, including four meat-packing businesses, six iron or steel plants, a smelter for precious metals, seven equipment manufacturers of various kinds, two large paint factories, three other chemical works, and three food packing establishments.

The major manufacturers closed, and new development was focused on office parks, housing, high-rise hotels, and yacht harbors.

The microclimate of South San Francisco is dominated by wind from the nearby Pacific Ocean, which typically keeps the daytime temperatures quite cool year round, even during the summer months.

There are also developments of two-and-three bedroom condominiums in the Westborough district and on El Camino Real near the South San Francisco BART station.

South San Francisco does not levy gross receipts or payroll taxes, although companies have to pay a business fee of up to $125,000 per year.

Small pockets of farmland still exist near San Bruno Mountain, but these lands have, over the years, been replaced by residential subdivisions.

Many other biotech companies, such as Exelixis, have also started or moved to South San Francisco to be in proximity to UCSF, Stanford University, and UC Berkeley; all are within an hour's drive.

"[27] The headquarters and main factory of See's Candies is located in South San Francisco, having moved from the original plant in Los Angeles due to the cooler weather.

[33] The Grand Avenue Library also has a collection of paintings and lithographs by WPA artists, including Maurice Del Mue and Suzanne Scheuer.

It was designed to "take advantage of the viewer’s motion… constantly changing, presenting a series of graceful ellipses and a shifting light pattern.

The South San Francisco BART station displays a series of murals based on historic photographs of the city and its people which may be viewed from the transit platform.

[41] In 2020, James Coleman defeated 18-year incumbent Richard Garbarino to become the youngest and first openly LGBTQ member of the city council.

[42] On January 26, 2021, the city council appointed Eddie Flores to fill a vacancy left by Councilmember Karyl Matsumoto, who did not run for reelection in 2020.

[48] The city's small downtown and several residential subdivisions, such as Mayfair Village, Sunshine Gardens, Avalon Park, Winston Manor, West Winston Manor, and Rancho Buri Buri, are located west of Highway 101, while the area east of Highway 101 is dominated by industrial complexes interspersed with modern office parks, particularly near the Oyster Point Marina on San Francisco Bay.

The extreme western portions of the city near Interstate 280 sit along a hillside and offer views of San Francisco Bay.

Grand Avenue, between Spruce and Airport, is zoned "Downtown Core" by the City of South San Francisco,[49] with various small shops and restaurants.

During the 2020 pandemic, when access to many state and county parks and trails became restricted, the number of hikers climbing to the top of Sign Hill rose to more than thirty per day.

A Municipal Services Building on Arroyo Drive near El Camino Real houses the Council Chambers, as well as event spaces.

The Police Department is (starting 2022) housed in a dedicated newly constructed building at Chestnut Avenue and Antoinette Lane.

SSF Unified School District facilities are also available for sports, and the Boys and Girls Club of Northern San Mateo County is headquartered adjacent to Orange and Centennial Parks.

The Class I bicycle and pedestrian trail is a 10' wide asphalt pathway with 2' decomposed granite shoulders, irrigated for low-maintenance landscaping, with safety lighting, signalized intersections where the trail crosses Spruce and Chestnut Avenues, and in-ground flashing lights at Orange Avenue.

The 1912 Metropolitan Hotel (built by the Meat Packers Consortium) now has a mural depicting SSF History high on its east wall.

Bertolucci's is an Italian restaurant that has also been around almost since the birth of the city, located in close proximity to downtown South San Francisco and is easily seen from highway 101.

Every Holiday season residents of Parkway Estates (a three-street development built in the mid-1980s off Chestnut Avenue) decorate their houses and yards with Christmas lights.

Few of the original residents survive and decorative technology today has far surpassed the 1960s era, so, in the 21st century, Lilac Lane has become a backwater.

A BART station, located directly adjacent to El Camino High School and Solaire Transit Village, provides near-express rapid transit service to SFO (with stops only in San Bruno and, on Red Line trains, Millbrae), as well as the cities of San Francisco, Oakland, Richmond, Antioch, Berkeley, Concord and Walnut Creek.

The city also lies along the historic El Camino Real between Colma and San Bruno, and is bordered on the west by Skyline Boulevard.