San Fierro is the smallest metropolitan area in San Andreas, situated on a peninsula in the western part of the state. South of the city lies the massive Mount Chiliad and the small town of Angel Pine in Whetstone. To the north of the city, across a re-creation of the famous Golden Gate Bridge (Gant Bridge), lies the town of Bayside, and northeast of the city lies the county of Tierra Robada. San Fierro is a moderately sized city with the beautiful San Fierro Bay to the north and The Panopticon to the east. San Fierro is connected to Los Santos and Las Venturas by road, rail and air.
There is a sizeable country club complete with a golf course within San Fierro. One of Carl Johnson's girlfriends, Katie Zhan, exercises here a lot when not at the dojo. In addition to this, San Fierro has a district (Queens) marked by rainbow signs that is meant to emulate San Francisco's famous Castro district, home to a sizeable gay population. San Fierro is also home to the football team the San Fierro 69ers, a double entendre referring to both the San Francisco 49ers and the "69" sexual position. Furthermore, in a crude reference to anal sex, the city's baseball team, the San Fierro Packers, is sponsored by none other than Fierro Fudge.
The city bears visible scars of an earthquake, a likely reference to the Loma Prieta earthquake of 1989, 3 years before the game takes place, though dialogue suggests that an earthquake has occurred just recently. The most obvious sign of the intense damage is the crumbled section of freeway lying to the immediate west of Garver Bridge's San Fierro approach, which is an apparent emulation of the damage done to San Francisco's Embarcadero Freeway, whose remnants could be seen for years after the earthquake. The freeway section does not seem to have any visible connection to the existing freeway, however. The city's infrastructure and buildings are not visibly damaged from the earthquake, the only such damage being in the Doherty area.
San Fierro commonly experiences rainstorms. These, combined with the frequent late-night and early-morning fog, can make driving and flying difficult because of reduced visibility. To further complicate the city's weather patterns, the Tierra Robada sandstorms occasionally blow into the northeastern parts of San Fierro, making flying near the Garver Bridge and Downtown skyline extremely treacherous.
Because San Fierro is meant to emulate San Francisco, many of its districts are re-imaginings of real neighborhoods in San Francisco:
- Battery Point - Fort Point
- Juniper Hollow - Cow Hollow
- Paradiso - The Presidio
- Esplanade North - Fisherman's Wharf
- Esplanade East - Embarcadero
- Downtown/Financial - Financial District
- Calton Heights - Pacific Heights
- Chinatown - Chinatown
- Juniper Hill - Russian Hill
- Palisades - Presidio Heights
- Santa Flora - Twin Peaks
- City Hall - City Hall/Civic Center
- Queens - The Castro
- King's - Noe Valley (and Pierre Valley)
- Easter Basin - China Basin/Hunters Point
- Doherty - Dogpatch
- Garcia - The Mission
- Hashbury - Haight-Ashbury
- Ocean Flats - Ocean Beach
- Avispa Country Club - Cliff House
- Missionary Hill - Mount Sutro
- Foster Valley - Foster City/Peninsula
- Easter Bay International Airport - San Francisco International Airport
As with every other city in San Andreas, there are emulated landmarks. In San Fierro, these include:
- The Transamerica Pyramid is re-created as the Big Pointy Building. One can travel to the top for a bird's eye view of San Fierro. One parachute (and only one, so exercise caution) is provided, in case players have the urge to jump off.
- The Golden Gate Bridge makes an appearance as the Gant Bridge. This bridge links San Fierro and the town of Bayside. The bridge appears to have functioning tollbooths, as evidenced by the fact that cars heading into San Fierro stop at the toll plaza. However, the player is apparently immune to the toll. Gant Bridge extends over San Fierro Bay, which is a re-creation of San Francisco Bay, and physically separates San Fierro from Bayside and Tierra Robada.
- The San Francisco Bay Bridge makes an appearance as the Garver Bridge. This bridge links San Fierro and Tierra Robada near Las Venturas. Alongside the Garver Bridge is the Kincaid Bridge, which is modeled after the Forth Rail Bridge, which itself sits beside the Forth Road Bridge outside Edinburgh, Scotland. This may also be a reference to the home of Rockstar North, where the original bridges are located. The Forth Road Bridge and the western span of the San Francisco-Oakland Bay Bridge look remarkably similar.
- Lombard Street, known as the "crookedest street", appears as Windy Windy Windy Windy Street in San Fierro's Calton Heights.
- Fort Point makes an appearance as Battery Point in the game, which sits underneath Gant Bridge. However, the fort has been taken over by the pimp Jizzy B, and is known as Jizzy's Pleasure Domes.
- The Castro district is emulated as "Queens", a tongue-in-cheek reference to the neighborhood as being the heart of San Francisco's gay community.
- San Fierro City Hall, based on the Beaux-Arts styled San Francisco City Hall, is located at the west end of Queens.
- A replica of Mount Sutro's radio antenna (Sutro Tower) is located atop Missionary Hill, at the south end of San Fierro. An observation area is located nearby, offering a pristine view of the city's southern side.
- Foster Valley, located between Missionary Hill and Easter Bay Airport, may be inspired from planned cities such as Foster City (which may explain the origin of the name as well). The contemporary buildings in the area, as well as a row of identical cylindrical buildings along an artificial lake (Zombotech Corporation headquarters), mildly resemble Oracle Corporation's World Headquarters at Redwood Shores, Redwood City, which is, coincidentally, also located near Foster City.
- Forth Bridge
- Ferry Building
- Grace Cathedral
- Golden Gate Park
- Fort Mason
- Presidio of San Francisco
- Cathedral of Saint Mary of the Assumption
- San Francisco Opera
- San Francisco cable car system
- Great Highway
Although cars are prominent, there are cable cars (trams) that circle San Fierro. Players are, however, unable to ride them, as they are literally unstoppable, and will plow through any obstacle without incurring damage.
The Easter Bay Airport is located at the southeast of the city, off Exit 3, the second to last exit, from the Garver Bridge Approach.
After a deadly shootout under the Mulholland Intersection in Los Santos, Carl Johnson is dragged by Officers Tenpenny and Pulaski to the little town of Angel Pine, where they deposit him, using the recent incarceration of Carl's brother Sweet as leverage to convince him to do their dirty work, which includes murdering witnesses. Along the way, Tenpenny employs Carl to help him obtain crack, and introduces him to the pot-growing hippie, The Truth. At this point in time, Cesar calls Carl, informing him that his gang has been disbanded, and that his life is now in danger. After escaping Los Santos, Cesar meets with Carl, and they street-race with the mysterious Wu Zi Mu. After Carl participates in some very poorly planned and executed robberies with Cesar's cousin, Catalina, he flees to San Fierro with The Truth.
Once there, Carl finds that all is wrong. The garage he won in a street race with Catalina is derelict, and he discovers the disturbing truth about the Loco Syndicate, the crime organization responsible for the spread of drugs in Los Santos. The syndicate is run by Mike Toreno, a shady person with a surprising background. T-Bone Mendez, a San Fierro Rifa, serves as the muscle of the organization, along with Ryder, CJ's homie from Grove Street, and Jizzy B, the biggest pimp in town. As he is investigating the Loco Syndicate, Carl also discovers that Wu Zi Mu (Woozie) is actually the head of a San Fierro Triad gang, the Mountain Cloud Boys, who are in the midst of a war with the Da Nang Boys, a Vietnamese crime organization.
After many odd jobs and errands for multiple bosses, Carl, Woozie and Cesar decide to take down the Loco Syndicate from the inside. Carl first pays Jizzy a visit, offering Jizzy his services. Jizzy gives Carl some work, during which he meets T-Bone Mendez and Mike Toreno. After being sure that Jizzy didn't suspect him, Carl confronted him at the Pleasure Domes nightclub. A massive shootout was followed by a high-speed car chase, in which Jizzy was killed by Carl. Then, he heads down to Pier 69, and kills T-Bone and Ryder in a massive shootout between Triads, San Fierro Rifa, Ballas, Carl and Cesar. Finally, Woozie informs him that Toreno is getting ready to leave in a helicopter, and Carl shoots him down with a rocket launcher. He then destroys the syndicate's crack lab in Doherty, ending the Loco Syndicate once and for all.
Carl then receives a mysterious call from a "friend" who claims knowledge of Sweet's whereabouts, prompting him to head out to the desert, to find none other than Mike Toreno. From there, a new chapter in the San Andreas storyline unfolds.