Sedimentation and nutrient loading are among the most prevalent threats to fluvial ecosystem integrity. This study employed artificial streams (mesocosms) to simulate individual and combined impacts of nutrient enrichment and deposited fine sediment on benthic biota. Ninety-six circular mesocosms were used in a 21-day crossed experiment that measured the impact of three substrate compositions (0, 25, and 50% fines <2 mm) and four nitrogen concentrations (17, 22, 43, and 94 μg L–1 (soluble inorganic nitrogen)) on periphyton and benthic macroinvertebrate assemblages. Permutational multivariate analysis of variance (PERMANOVA) of macroinvertebrate assemblages indicated substantial shifts in structural composition, while univariate models for Lepidostomatidae and total Ephemeroptera, Plecoptera and Trichoptera revealed that nutrient and sediment subsidies related to single factors were suppressed by an additional stressor. Stressor mechanism overlap was evident at higher treatment levels, as moderate nutrient enrichment increased nutritional resources but high nitrogen concentrations lead to substrate smothering by periphyton, contributing to habitat degradation originating from inorganic sedimentation. Our study is consistent with research showing that nutrient loading and sedimentation interact to deteriorate lotic systems beyond levels attributable to either individual stressor. Management practices and pollution standards need to incorporate relationships between stressors tightly co-vary in natural settings.