San Bruno is located at 37°37′31″N, 122°25′31″W (37.625288, -122.425266) GR1 . The city is located between South San Francisco and Millbrae, near the San Francisco International Airport and about 12 miles (19 km) south of downtown San Francisco.

According to the United States Census Bureau, the city has a total area of 14.1 km² (5.5 mi²), all land. The city spreads from the mostly flat lowlands near San Francisco Bay into the foothills of the Santa Cruz Mountains, which rise to more than 600 feet above sea level (183 m) in Crestmoor and more than 700 feet (213 m) above sea level in the northwestern corner of the city. San Bruno City Hall sits at an official elevation of 41 feet (12.5 m) above sea level.

Portions of Mills Park, Crestmoor, and Rollingwood are very hilly and feature some canyons and ravines. Creeks, many of them now in culverts, flow from springs in the hills toward San Francisco Bay. Just west of Skyline Boulevard is San Andreas Lake, outside the city limits, which gave its name to the famous San Andreas Fault in 1895. The lake is actually one of several reservoirs used by the San Francisco Water Department.

San Bruno City Park, bordered by Crystal Springs Avenue and El Crystal School, is the major municipal park. It offers shaded walkways and hiking trials, picnic tables, a playground, a small ballpark, a municipal swimming pool, and a recreation center that includes an indoor basketball court once used for training by the San Francisco Warriors basketball team. There are smaller municipal parks in other parts of the city.

Junipero Serra County Park, also accessible from Crystal Springs Avenue, is a 100-acre (.405 square kilometer) park owned by San Mateo County and includes numerous hiking trails, as well as picnic shelters, barbecue pits, and picnic tables. The wilderness area was named for Junipero Serra, a Franciscan friar who founded many of the Spanish missions in California during the eighteenth century; Serra regularly passed through what is now San Bruno whenever he visited the mission at San Francisco. The park is administered by the San Mateo County Parks and Recreation Department, which charges a small entry fee on weekends.