San Lorenzo is located on the Rancho San Lorenzo Mexican land grant given to Guillermo Castro in 1841. San Lorenzo was mostly farmland, a significant center of production of fruit and flowers, from the mid-19th century to the mid-20th century.

Many of the early inhabitants have been laid to rest in Pioneer Cemetery, including Moses Wicks, who brought oysters to San Leandro Bay (by boat around the cape) from Patchogue, Long Island.

In 1944, under contract to the U.S. Navy, David Bohannon’s Greenwood Company began construction of San Lorenzo Village, a tract of two- and three-bedroom homes for workers in the East Bay’s war industries. San Lorenzo Village was one of the nation’s first planned communities, with parcels designated for schools, churches, parks, and several retail centers. Bohannon’s pioneering pre-cutting techniques, referred to as the “California method,” were used in later developments, such as the more famous Levittown, Pennsylvania. Home construction continued into the 1950s to accommodate the region’s booming population.

The first post office opened in San Lorenzo in 1854.