The earliest archaeological evidence of human habitation of the territory of the city of San Francisco dates to 3000 BC. The Yelamu group of the Ohlone people resided in a few small villages when an overland Spanish exploration party, led by Don Gaspar de Portolá, arrived on November 2, 1769, the first documented European visit to San Francisco Bay. The first maritime presence occurred on August 5, 1775, when San Carlos—commanded by Juan Manuel de Ayala—became the first ship to anchor in the bay. The following year, on March 28, 1776, the Spanish established the Presidio of San Francisco, followed by a mission, Mission San Francisco de Asís (Mission Dolores), established by the Spanish explorer Juan Bautista de Anza.

Upon independence from Spain in 1821, the area became part of Mexico. Under Mexican rule, the mission system gradually ended, and its lands became privatized. In 1835, William Richardson, a naturalized Mexican citizen of English birth, erected the first independent homestead, near a boat anchorage around what is today Portsmouth Square. Together with Alcalde Francisco de Haro, he laid out a street plan for the expanded settlement, and the town, named Yerba Buena, began to attract American settlers. Commodore John D. Sloat claimed California for the United States on July 7, 1846, during the Mexican–American War, and Captain John B. Montgomery arrived to claim Yerba Buena two days later. Yerba Buena was renamed San Francisco on January 30 of the next year, and Mexico officially ceded the territory to the United States at the end of the war in 1848. Despite its attractive location as a port and naval base, San Francisco was still a small settlement with inhospitable geography.

The California Gold Rush brought a flood of treasure seekers (known as "forty-niners", as in "1849"). With their sourdough bread in tow, prospectors accumulated in San Francisco over rival Benicia, raising the population from 1,000 in 1848 to 25,000 by December 1849. The promise of great wealth was so strong that crews on arriving vessels deserted and rushed off to the gold fields, leaving behind a forest of masts in San Francisco harbor. Some of these approximately 500 abandoned ships were used at times as storeships, saloons and hotels; many were left to rot and some were sunk to establish title to the underwater lot. By 1851, the harbor was extended out into the bay by wharves while buildings were erected on piles among the ships. By 1870, Yerba Buena Cove had been filled to create new land. Buried ships are occasionally exposed when foundations are dug for new buildings.

California was quickly granted statehood in 1850, and the U.S. military built Fort Point at the Golden Gate and a fort on Alcatraz Island to secure the San Francisco Bay. Silver discoveries, including the Comstock Lode in Nevada in 1859, further drove rapid population growth. With hordes of fortune seekers streaming through the city, lawlessness was common, and the Barbary Coast section of town gained notoriety as a haven for criminals, prostitution, and gambling.

Entrepreneurs sought to capitalize on the wealth generated by the Gold Rush. Early winners were the banking industry, with the founding of Wells Fargo in 1852 and the Bank of California in 1864. Development of the Port of San Francisco and the establishment in 1869 of overland access to the eastern U.S. rail system via the newly completed Pacific Railroad (the construction of which the city only reluctantly helped support) helped make the Bay Area a center for trade. Catering to the needs and tastes of the growing population, Levi Strauss opened a dry goods business and Domingo Ghirardelli began manufacturing chocolate. Chinese immigrants made the city a polyglot culture, drawn to "Old Gold Mountain", creating the city's Chinatown quarter. In 1870, Asians made up 8% of the population. The first cable cars carried San Franciscans up Clay Street in 1873. The city's sea of Victorian houses began to take shape, and civic leaders campaigned for a spacious public park, resulting in plans for Golden Gate Park. San Franciscans built schools, churches, theaters, and all the hallmarks of civic life. The Presidio developed into the most important American military installation on the Pacific coast. By 1890, San Francisco's population approached 300,000, making it the eighth-largest city in the United States at the time. Around 1901, San Francisco was a major city known for its flamboyant style, stately hotels, ostentatious mansions on Nob Hill, and a thriving arts scene. The first North American plague epidemic was the San Francisco plague of 1900–1904.

At 5:12 am on April 18, 1906, a major earthquake struck San Francisco and northern California. As buildings collapsed from the shaking, ruptured gas lines ignited fires that spread across the city and burned out of control for several days. With water mains out of service, the Presidio Artillery Corps attempted to contain the inferno by dynamiting blocks of buildings to create firebreaks. More than three-quarters of the city lay in ruins, including almost all of the downtown core. Contemporary accounts reported that 498 people lost their lives, though modern estimates put the number in the several thousands. More than half of the city's population of 400,000 was left homeless.Refugees settled temporarily in makeshift tent villages in Golden Gate Park, the Presidio, on the beaches, and elsewhere. Many fled permanently to the East Bay.

Rebuilding was rapid and performed on a grand scale. Rejecting calls to completely remake the street grid, San Franciscans opted for speed.Amadeo Giannini's Bank of Italy, later to become Bank of America, provided loans for many of those whose livelihoods had been devastated. The influential San Francisco Planning and Urban Research Association or SPUR was founded in 1910 to address the quality of housing after the earthquake. The earthquake hastened development of western neighborhoods that survived the fire, including Pacific Heights, where many of the city's wealthy rebuilt their homes. In turn, the destroyed mansions of Nob Hill became grand hotels. City Hall rose again in splendid Beaux Arts style, and the city celebrated its rebirth at the Panama–Pacific International Exposition in 1915.

It was during this period San Francisco built some of its most important infrastructure. Civil Engineer Michael O'Shaughnessy was hired by San Francisco Mayor James Rolph as chief engineer for the city in September 1912 to supervise the construction of the Twin Peaks Reservoir, the Stockton Street Tunnel, the Twin Peaks Tunnel, the San Francisco Municipal Railway, the Auxiliary Water Supply System, and new sewers. San Francisco's streetcar system, of which the J, K, L, M, and N lines survive today, was pushed to completion by O'Shaughnessy between 1915 and 1927. It was the O'Shaughnessy Dam, Hetch Hetchy Reservoir, and Hetch Hetchy Aqueduct that would have the largest effect on San Francisco. An abundant water supply enabled San Francisco to develop into the city it has become today.

In ensuing years, the city solidified its standing as a financial capital; in the wake of the 1929 stock market crash, not a single San Francisco-based bank failed. Indeed, it was at the height of the Great Depression that San Francisco undertook two great civil engineering projects, simultaneously constructing the San Francisco–Oakland Bay Bridge and the Golden Gate Bridge, completing them in 1936 and 1937, respectively. It was in this period that the island of Alcatraz, a former military stockade, began its service as a federal maximum security prison, housing notorious inmates such as Al Capone, and Robert Franklin Stroud, the Birdman of Alcatraz. San Francisco later celebrated its regained grandeur with a World's fair, the Golden Gate International Exposition in 1939–40, creating Treasure Island in the middle of the bay to house it.^{[citation needed]}

During World War II, the Hunters Point Naval Shipyard became a hub of activity, and Fort Mason became the primary port of embarkation for service members shipping out to the Pacific Theater of Operations. The explosion of jobs drew many people, especially African Americans from the South, to the area. After the end of the war, many military personnel returning from service abroad and civilians who had originally come to work decided to stay. The United Nations Charter creating the United Nations was drafted and signed in San Francisco in 1945 and, in 1951, the Treaty of San Francisco re-established peaceful relations between Japan and the Allied Powers.

Urban planning projects in the 1950s and 1960s involved widespread destruction and redevelopment of west-side neighborhoods and the construction of new freeways, of which only a series of short segments were built before being halted by citizen-led opposition. The onset of containerization made San Francisco's small piers obsolete, and cargo activity moved to the larger Port of Oakland. The city began to lose industrial jobs and turned to tourism as the most important segment of its economy. The suburbs experienced rapid growth, and San Francisco underwent significant demographic change, as large segments of the white population left the city, supplanted by an increasing wave of immigration from Asia and Latin America. From 1950 to 1980, the city lost over 10 percent of its population.

Over this period, San Francisco became a magnet for America's counterculture. Beat Generation writers fueled the San Francisco Renaissance and centered on the North Beach neighborhood in the 1950s.Hippies flocked to Haight-Ashbury in the 1960s, reaching a peak with the 1967 Summer of Love. In 1974, the Zebra murders left at least 16 people dead. In the 1970s, the city became a center of the gay rights movement, with the emergence of The Castro as an urban gay village, the election of Harvey Milk to the Board of Supervisors, and his assassination, along with that of Mayor George Moscone, in 1978.

Bank of America completed 555 California Street in 1969 and the Transamerica Pyramid was completed in 1972, igniting a wave of "Manhattanization" that lasted until the late 1980s, a period of extensive high-rise development downtown. The 1980s also saw a dramatic increase in the number of homeless people in the city, an issue that remains today, despite many attempts to address it. The 1989 Loma Prieta earthquake caused destruction and loss of life throughout the Bay Area. In San Francisco, the quake severely damaged structures in the Marina and South of Market districts and precipitated the demolition of the damaged Embarcadero Freeway and much of the damaged Central Freeway, allowing the city to reclaim The Embarcadero as its historic downtown waterfront and revitalizing the Hayes Valley neighborhood.^{[citation needed]}

Two recent decades have seen two booms driven by the internet industry. First was the dot-com boom of the late 1990s, startup companies invigorated the San Francisco economy. Large numbers of entrepreneurs and computer application developers moved into the city, followed by marketing, design, and sales professionals, changing the social landscape as once-poorer neighborhoods became increasingly gentrified. Demand for new housing and office space ignited a second wave of high-rise development, this time in the South of Market district. By 2000, the city's population reached new highs, surpassing the previous record set in 1950. When the bubble burst in 2001, many of these companies folded and their employees were laid off. Yet high technology and entrepreneurship remain mainstays of the San Francisco economy. By the mid-2000s (decade), the social media boom had begun, with San Francisco becoming a popular location for tech offices and a common place to live for people employed in Silicon Valley companies such as Apple and Google.

The Ferry Station Post Office Building, Armour & Co. Building, Atherton House, and YMCA Hotel are historic buildings among dozens of historical landmarks in the city according to the National Register of Historic Places listings in San Francisco.^{[citation needed]}

The U.S. Census Bureau estimates San Francisco's population to be 881,549 as of July 1, 2019, with a population density of 18,838/sq mi. With roughly one-quarter the population density of Manhattan, San Francisco is the second-most densely populated large American city, behind only New York City among cities greater than 200,000 population, and the fifth-most densely populated U.S. county, following only four of the five New York City boroughs.

San Francisco forms part of the five-county San Francisco–Oakland–Hayward, CA Metropolitan Statistical Area, a region of 4.7 million people, and has served as its traditional demographic focal point. It is also part of the greater 14-county San Jose-San Francisco-Oakland, CA Combined Statistical Area, whose population is over 9.6 million, making it the fifth-largest in the United States as of 2018.

San Francisco has a majority minority population, as non-Hispanic whites comprise less than half of the population, 41.9%, down from 92.5% in 1940. As of the 2010 census, the ethnic makeup and population of San Francisco included: 390,387 Whites (48%), 267,915 Asians (33%), 48,870 African Americans (6%), and others. There were 121,744 Hispanics or Latinos of any race (15%).

In 2010, residents of Chinese ethnicity constituted the largest single ethnic minority group in San Francisco at 21% of the population; the other Asian groups are Filipinos (5%) and Vietnamese (2%). The population of Chinese ancestry is most heavily concentrated in Chinatown, Sunset District, and Richmond District, whereas Filipinos are most concentrated in the Crocker-Amazon (which is contiguous with the Filipino community of Daly City, which has one of the highest concentrations of Filipinos in North America), as well as in SoMa. The Tenderloin District is home to a large portion of the city's Vietnamese population as well as businesses and restaurants, which is known as the city's Little Saigon.

The principal Hispanic groups in the city were those of Mexican (7%) and Salvadoran (2%) ancestry. The Hispanic population is most heavily concentrated in the Mission District, Tenderloin District, and Excelsior District. The city's percentage of Hispanic residents is less than half of that of the state. The population of African Americans in San Francisco is 6% of the city's population. The percentage of African Americans in San Francisco is similar to that of California. The majority of the city's black population reside within the neighborhoods of Bayview-Hunters Point, Visitacion Valley, and in the Fillmore District.

According to a 2014 study by the Pew Research Center, the largest religious groupings in San Francisco's metropolitan area are Christians (48%), followed by those of no religion (35%), Hindus (5%), Jews (3%), Buddhists (2%), Muslims (1%) and a variety of other religions have smaller followings. According to the same study by the Pew Research Center, about 20% of residents in the area are Protestant, and 25% professing Roman Catholic beliefs. Meanwhile, 10% of the residents in metropolitan San Francisco identify as agnostics, while 5% identify as atheists.

As of 2010, 55% (411,728) of San Francisco residents spoke only English at home, while 19% (140,302) spoke a variety of Chinese (mostly Taishanese and Cantonese), 12% (88,147) Spanish, 3% (25,767) Tagalog, and 2% (14,017) Russian. In total, 45% (342,693) of San Francisco's population spoke a language at home other than English.

San Francisco has several prominent Chinese, Mexican, and Filipino ethnic neighborhoods including Chinatown and the Mission District. Research collected on the immigrant clusters in the city show that more than half of the Asian population in San Francisco is either Chinese-born (40.3%) or Philippine-born (13.1%), and of the Mexican population 21% were Mexican-born, meaning these are people who recently immigrated to the United States. Between the years of 1990 and 2000, the number foreign born residents increased from 33% to nearly 40%, During this same time period, the San Francisco Metropolitan area received 850,000 immigrants, ranking third in the United States after Los Angeles and New York.

Of all major cities in the United States, San Francisco has the second-highest percentage of residents with a college degree, behind only Seattle. Over 44% of adults have a bachelor's or higher degree. San Francisco had the highest rate at 7,031 per square mile, or over 344,000 total graduates in the city's 46.7 square miles (121 km²).

San Francisco has the highest estimated percentage of gay and lesbian individuals of any of the 50 largest U.S. cities, at 15%. San Francisco also has the highest percentage of same-sex households of any American county, with the Bay Area having a higher concentration than any other metropolitan area.

San Francisco ranks third of American cities in median household income with a 2007 value of $65,519. Median family income is $81,136. An emigration of middle-class families has left the city with a lower proportion of children than any other large American city, with the dog population cited as exceeding the child population of 115,000, in 2018. The city's poverty rate is 12%, lower than the national average.Homelessness has been a chronic problem for San Francisco since the early 1970s. The city is believed to have the highest number of homeless inhabitants per capita of any major U.S. city.

There are 345,811 households in the city, out of which: 133,366 households (39%) were individuals, 109,437 (32%) were opposite-sex married couples, 63,577 (18%) had children under the age of 18 living in them, 21,677 (6%) were unmarried opposite-sex partnerships, and 10,384 (3%) were same-sex married couples or partnerships. The average household size was 2.26; the average family size was 3.11. 452,986 people (56%) lived in rental housing units, and 327,985 people (41%) lived in owner-occupied housing units. The median age of the city population is 38 years.

San Francisco "declared itself a sanctuary city in 1989, and city officials strengthened the stance in 2013 with its 'Due Process for All' ordinance. The law declared local authorities could not hold immigrants for immigration officials if they had no violent felonies on their records and did not currently face charges." The city issues a Resident ID Card regardless of the applicant's immigration status.

Homelessness, historically, has been a major problem in the city and remains a growing problem in modern times.

8,035 homeless people were counted in San Francisco's 2019 point-in-time street and shelter count. This was an increase of more than 17% over the 2017 count of 6,858 people. 5,180 of the people were living unsheltered on the streets and in parks. 26% of respondents in the 2019 count identified job loss as the primary cause of their homelessness, 18% cited alcohol or drug use, and 13% cited being evicted from their residence. The city of San Francisco has been dramatically increasing its spending to service the growing population homelessness crisis: spending jumped by $241 million in 2016–17 to total $275 million, compared to a budget of just $34 million the previous year. In 2017–18 the budget for combatting homelessness stood at $305 million. In the 2019–2020 budget year, the city budgeted $368 million for homelessness services. In the propose 2020–2021 budget the city budgeted $850 million for homelessness services.

In January 2018 a United Nations special rapporteur on homelessness, Leilani Farha, stated that she was "completely shocked" by San Francisco's homelessness crisis during a visit to the city. She compared the "deplorable conditions" of the homeless camps she witnessed on San Francisco's streets to those she had seen in Mumbai. In May 2020, San Francisco officially sanctioned homeless encampments.