San Lorenzo is located on the route of El Camino Viejo on land of the former Rancho San Lorenzo a Mexican land grant given to Guillermo Castro in 1841, and the former Rancho San Leandro, granted to José Joaquin Estudillo in 1842.
The first post office opened in San Lorenzo in 1854.
Many of the early inhabitants have been laid to rest in San Lorenzo Pioneer Cemetery, including Moses Wicks, who brought oysters to San Leandro Bay (by boat around the cape) from Patchogue, Long Island.. The cemetery is maintained by the county and the Hayward Area Historical Society.
San Lorenzo was mostly farmland, a significant center of production of fruit and flowers, from the mid-19th century to the mid-20th century.
In 1944, under contract to the U.S. Navy, David D. 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.