We studied the associations of crayfish with reach-scale instream habitat and water quality variables and watershed-scale variables of riparian and watershed land cover, runoff, impervious surfaces, and hydrologic soil type in west-central Indiana. Crayfish assemblage was measured by abundance, species richness, and diversity (Shannon's H) at 180 sites. The western portion of the study area, within the Interior River Lowland ecoregion, has been heavily impacted by agriculture, while the eastern portion, within the Interior Plateau ecoregion, is more heavily wooded and less impacted. The ability of variables at each spatial extent to predict crayfish assemblage was assessed using multiple linear regression analysis. Reach-scale models were better predictors of crayfish assemblage than watershed-scale models. A variety of habitat and water quality characteristics, principally instream cover, appeared as important predictors. Forested riparian and watershed land appeared as significant watershed-scale predictors. Reach-scale models were also better predictors of individual species abundance. Model predictive power was similar when developed separately for the two ecoregions of the study area, indicating that extent of agricultural development had little effect on the ability of variables at a given spatial scale to predict crayfish assemblage. Results indicate that reach-scale variables are more powerful in predicting crayfish assemblage, and important factors to consider in crayfish management are maintaining ample instream cover and intact riparian areas.