Microbial populations involved in forming the distinctive precipitates of the S, Fe, Mn, and Ca cycles in the San Diego River watershed reflect an interplay between mineralogy of the rocks in the watershed, sparse rainfall, ground- and surface-water anoxia, and runoff of high sulfate, treated imported water. In the less developed headwaters, Temescal Creek tributary emerges from pyrite-bearing metamorphic rocks, and thus exhibits both an oxidized Fe and reduced S cycle. In the middle reaches, the river moves through developed land where treated, imported high sulfate Colorado River water enters from urban runoff. Mast Park surrounded by caliche-bearing sedimentary rocks is a site where marl is precipitating. Cobbles in riffles in the river are coated black with Mn oxide. When the river encounters deep-seated volcanic bedrock, it wells up to precipitate both Fe and Mn oxides at Old Mission Dam. Then, directly flowing through caliche-laced sedimentary rocks, Birchcreek tributary precipitates tufa. Further downstream, at a site that periodically receives full sunlight, a sulfuretum sets up during the summer when the river is deoxygenated. Such a rich geochemistry results in activity of iron and manganese oxidizing bacteria, sulfur oxidizers and reducers, and cyanobacteria precipitating calcareous marl and tufa.