Understanding the complex relations between multiple environmental stressors and ecological conditions in streams can help guide resource-management decisions. During 14 weeks in spring/summer 2013, personnel from the US Geological Survey and the US Environmental Protection Agency sampled 98 wadeable streams across the Midwest Corn Belt region of the USA for water and sediment quality, physical and habitat characteristics, and ecological communities. We used these data to develop independent predictive disturbance models for 3 macroinvertebrate metrics and a multimetric index. We developed the models based on boosted regression trees (BRT) for 3 stressor categories, land use/land cover (geographic information system [GIS]), all in-stream stressors combined (nutrients, habitat, and contaminants), and for GIS plus in-stream stressors. The GIS plus in-stream stressor models had the best overall performance with an average cross-validation R² across all models of 0.41. The models were generally consistent in the explanatory variables selected within each stressor group across the 4 invertebrate metrics modeled. Variables related to riparian condition, substrate size or embeddedness, velocity and channel shape, nutrients (primarily NH₃), and contaminants (pyrethroid degradates) were important descriptors of the invertebrate metrics. Models based on all measured in-stream stressors performed comparably to models based on GIS landscape variables, suggesting that the in-stream stressor characterization reasonably represents the dominant factors affecting invertebrate communities and that GIS variables are acting as surrogates for in-stream stressors that directly affect in-stream biota.