To improve understanding of human impacts on headwater stream condition, we quantified relationships between human, terrestrial landscape, and stream system variables in 29 central Iowa watersheds. Across study watersheds, between 0 and 100 % of total land area was characterized as “urban” (developed and barren land), whereas cultivated land constituted between 0 and 71 % of watershed area. Several variables were measured for each stream and associated watershed. Strengths of correlative relationships were used to select variables for path analysis, which we used to gain insight into factors affecting stream condition by evaluating direct and indirect effects of human system variables, terrestrial landscape variables, and physical stream variables on stream invertebrates. Results indicated that in predominantly urban watersheds, contaminant inputs to streams (measured by streamwater conductivity) negatively affected invertebrates, including EPT taxa (Ephemeroptera, Plecoptera, Trichoptera), and streamwater contaminant concentrations increased with impervious surface and human population density in the watershed. In rural watersheds, high streamwater nitrogen concentrations associated with cultivated land were related to declines in invertebrate taxon richness. Independent of land use, invertebrate abundance and taxonomic diversity were positively related to coarse substrate abundance on the streambed. Additionally, stream flow (discharge) increased with watershed area, which in turn increased invertebrate taxonomic diversity. Apparently, mechanisms responsible for human impacts on stream condition in central Iowa depend on dominant land use in the watershed. Additionally, stream ecosystems with high quality benthic habitat, and those located in large watersheds with greater flow, appear to be more resilient to land use effects.