Almaden Valley takes its name from the New Almaden mercury mines at its southern end, and many of its streets keep the theme, such as Silver Lode Lane, Silver Mine Drive and the many places called Quicksilver. In the Mexican era its land was divided between Rancho San Vicente and Rancho Los Capitancillos.
In 1852 Charles LeFranc founded Almaden Vineyards here with vine cuttings from France; it is described as the first commercial winery in California, and the Old Almaden Winery site is now a park. The Graystone Quarry supplied stone for San Francisco City Hall, Stanford University and the Cathedral Basilica of St. Joseph. In 1959 the University of California picked the valley for a new campus, but land prices rose so fast that the plan fell through.