The SFSPCA was founded on April 18, 1868 by a banker named James Sloan Hutchinson. He intervened in the inhumane behavior of two men who were dragging a squealing boar off to market along the street's rough cobblestones. The incident moved Hutchinson to call together a group of fellow humanitarians to found The San Francisco SPCA. The SFSPCA is now the oldest U.S. animal welfare organization in the West.

After the 1906 San Francisco earthquake, the SFSPCA built horse troughs throughout the City to provide water for horses employed in rescue and rebuilding efforts. Plaques memorializing the troughs remain in place as of 2006.