Fish, habitat, and water chemistry data were collected from 98 streams in the midwestern United States, an area dominated by intense cultivation of row crops, in order to identify important water‐quality stressors to fish communities. We focused on 10 stressors including riparian disturbance, riparian vegetative cover, instream fish cover, streambed sedimentation, streamflow variability, total nitrogen, total phosphorus, minimum dissolved oxygen, pesticides, and bed sediment contaminants. Fish community response variables included a measure of observed/expected taxonomic completeness; species‐specific tolerances to nitrogen, phosphorus, dissolved oxygen, and water temperature; the percent of species classified as macrohabitat generalists; and an index of pesticide toxicity to fish. Multivariate analysis indicated that total nitrogen was the most important stressor, signifying that fish communities were responding to total nitrogen despite relatively high levels common to an agricultural setting. Individually, fish taxonomic completeness decreased with increasing streambed sedimentation, whereas fish community tolerance to total phosphorus increased with increasing streambed sedimentation, riparian disturbance, and total nitrogen. These findings underscore the importance of multiple biological response metrics to better understand the effects of water‐quality stressors on fish communities and highlight the complex relations between total phosphorus and fish communities.