Potrero Hill occupies a microclimate that is warmer and sunnier than much of San Francisco, sheltered from the fog by Twin Peaks and the hills to the west. The views from 20th Street facing north, looking across the city toward the downtown skyline, have become one of the most popular spots in San Francisco for engagement and wedding photographs. The neighborhood was historically working class, home to ironworks, shipyards, and industrial facilities along its eastern slope near the waterfront. The hilltop was residential, populated first by immigrants and later by artists and young families drawn by the views and the relative affordability.

Potrero Hill's eastern boundary has long been defined by industry. The Potrero Generating Station operated on the waterfront for decades, and Pier 70's shipyards once employed thousands. The San Francisco Flower Market moved to a new location at the base of Potrero Hill, opening in January 2025. The hill's western slope borders the Mission District, and its southern end approaches the Bayview neighborhood. The neighborhood's character varies dramatically by block: quiet Victorian streets on the hilltop give way to commercial corridors and former industrial parcels at lower elevations. The UCSF Mission Bay campus and Chase Center are visible from the eastern slopes.

Potrero Hill has resisted the dramatic transformations that have swept other San Francisco neighborhoods. Its hilltop location, limited public transit, and relatively small commercial district have kept it quieter than the Mission or SoMa. The 18th Street corridor serves as the neighborhood's main street, with cafes, restaurants, and small shops. The Potrero Hill Recreation Center provides community gathering space. Anchor Brewing Company operated in Potrero Hill for decades, and though the brewery closed in 2023, its legacy is woven into the neighborhood's identity. The hill remains what it has been for generations: a residential neighborhood where the views are spectacular, the weather is warm, and the crookedest street gets none of the credit.