The successful use of macroinvertebrates as indicators of stream condition in bioassessments has led to heightened interest throughout the scientific community in the prediction of stream condition. For example, predictive models are increasingly being developed that use measures of watershed disturbance, including urban and agricultural land-use, as explanatory variables to predict various metrics of biological condition such as richness, tolerance, percent predators, index of biotic integrity, functional species traits, or even ordination axes scores. Our primary intent was to determine if effective models could be developed using watershed characteristics of disturbance to predict macroinvertebrate metrics among disparate and widely separated ecoregions. We aggregated macroinvertebrate data from universities and state and federal agencies in order to assemble stream data sets of high enough density appropriate for modeling in three distinct ecoregions in Oregon and California. Extensive review and quality assurance of macroinvertebrate sampling protocols, laboratory subsample counts and taxonomic resolution was completed to assure data comparability. We used widely available digital coverages of land-use and land-cover data summarized at the watershed and riparian scale as explanatory variables to predict macroinvertebrate metrics commonly used by state resource managers to assess stream condition. The “best” multiple linear regression models from each region required only two or three explanatory variables to model macroinvertebrate metrics and explained 41–74% of the variation. In each region the best model contained some measure of urban and/or agricultural land-use, yet often the model was improved by including a natural explanatory variable such as mean annual precipitation or mean watershed slope. Two macroinvertebrate metrics were common among all three regions, the metric that summarizes the richness of tolerant macroinvertebrates (RICHTOL) and some form of EPT (Ephemeroptera, Plecoptera, and Trichoptera) richness. Best models were developed for the same two invertebrate metrics even though the geographic regions reflect distinct differences in precipitation, geology, elevation, slope, population density, and land-use. With further development, models like these can be used to elicit better causal linkages to stream biological attributes or condition and can be used by researchers or managers to predict biological indicators of stream condition at unsampled sites.