We attempted to discern the contributions of physical habitat, water chemistry, nutrients, and contaminants from historic lead–zinc mining activities on the riffle‐dwelling benthic fish community of the Spring River, a midwestern warmwater stream that originates in Missouri and flows into Kansas and Oklahoma. The Spring River has a fish community that includes the Neosho madtom Noturus placidus, a species federally listed as threatened. Although anthropogenic factors such as contaminants limited populations and densities of fishes, an integrated assessment of natural and anthropogenic factors was necessary to effectively estimate the influence of the latter. Fish populations in the Spring River, especially Neosho madtoms, seem to be limited by the presence of cadmium, lead, and zinc in water and in benthic invertebrate food sources and by physical habitat. The population density and community structure of fish in the Spring River also seem to be related to water chemistry and nutrients. Concurrently, diminished food availability may be limiting fish populations at some sites where Neosho madtoms are not found. Many of the natural factors that may be limiting Neosho madtom and other riffle‐dwelling fish populations in the Spring River probably are characteristic of the physiographic region drained by the upper reach and many of the tributaries of the Spring River. Our results indicate that competition between the Neosho madtom and other species within the riffle‐dwelling fish community is an unlikely cause of Neosho madtom population limitation in the Spring River.