San Francisco is the financial, cultural, and transportational center of the San Francisco Bay Area, a region which includes San Jose and Oakland. It encompasses a land area of about 46.9 square miles (121 km2) on the northern end of the San Francisco Peninsula, and is the second-most densely populated large city in the United States, after New York City. In 1776, Spanish colonists established a fort at the Golden Gate and a mission named for Saint Francis of Assisi ('Mission San Francisco de Asís') on the site. Upon independence from Spain in 1821, the area became part of Mexico but began to attract American migrants. Mexico officially ceded California to the United States at the end of the Mexican-American War in 1846. The California Gold Rush of 1849 transformed it into the largest city on the West Coast at the time. After three-quarters of the city was destroyed by the 1906 earthquake and fire, San Francisco was quickly rebuilt, and today San Francisco is renowned for its chilly summer fog, steep rolling hills, eclectic mix of Victorian and modern architecture, and its famous landmarks, including the Golden Gate Bridge, cable cars, and Chinatown. Across the Golden Gate Bridge in Marin County is the Muir Woods National Monument, home to a forest of ancient redwood trees.
Wild chimp Bright Eyes was taken from the jungles of West Africa to the Gen-Sys Laboratories in San Francisco, where she was experimented on by Dr. Will Rodman and his team. Her son, Caesar, was raised by Rodman in his San Francisco home and later housed at the nearby San Bruno Primate Shelter. After leading a mass breakout of genetically altered apes from the shelter, the laboratory and the San Francisco Zoo, Caesar tried to bring the apes to freedom in the Muir Woods Park redwood forest across the Golden Gate Bridge. Seeing only rampaging wild animals, the San Francisco authorities tried to corral the apes on the bridge and massacre them, but after a battle and many deaths on both sides, most apes survived and reached Muir Woods. (CE: Rise of the Planet of the Apes)
Around 3085, time-lost astronauts Alan Virdon and Pete Burke and their chimp ally Galen ventured into the ruins of San Francisco, largely destroyed by frequent earthquakes. They were prompted by human children from the nearby the village of Numai, who had found electrical components amongst the rubble. Pursued by gorilla soldiers, Burke and chief gorilla Urko fell through a chasm into a disused underground BART (Bay Area Rapid Transit) station, where they quickly became trapped. Only through the humans and apes working as a team were they rescued, with the fugitives then escaping the ancient city before Urko could arrest them. (TV: "The Trap") They would later also search the ruins of nearby Oakland. (TV: "The Legacy")
In a terrible battle thirty or forty miles north of San Francisco, gorilla and human armies slaughtered one another until only one human and one ape were alive. But Solomon the gorilla and Jovan the human, were seriously wounded: the human could not move his legs, the ape could not use his arms. In order to survive, they formed an uneasy truce and had to work together. They crossed the desert, battling mutated beasts, harsh weather and other obstacles. An ape/human hybrid named Mordecai, who lived as a hermit, provided shelter, food and healing. They resumed fighting once they were able, and Mordecai sadly cast them out, telling them to visit the city and see what hatred brings. Stunned at the devastation, they put aside their hatred and vowed to end the war, but they were soon caught in the crossfire between rival bands of Mutant Men and Mutant Apes squaring off to protect their ridges of rubble, and both were killed. (Marvel: Evolution's Nightmare)
- A 1975 timeline published in Marvel Comics' Planet of the Apes Magazine #11 identified San Francisco as the 'Modern City'/'Forbidden City' where the events of Conquest of the Planet of the Apes and Battle for the Planet of the Apes take place, but other sources identify it as Los Angeles, San Diego, New York City, or an entirely newly-built city.
- The 2005 fan-produced comic strip Going Home had Virdon, Burke and Galen return to the ruins of San Francisco and become separated permanently.