Ecological patterns and processes operate on multiple spatio-temporal scales and the multidimensional nature of rivers makes them appropriate ecosystems to study scale-dependent phenomena. However, the magnitude of short- and long-term temporal variation, and longitudinal, lateral, and vertical spatial complexity also make lotic ecosystems challenging systems to study. Macroinvertebrate communities respond to small- and large-scale environmental drivers, flow disturbance regimes (e.g., drought, flood). However, studies examining the relative influence of small- and large spatial scale environmental drivers in conjunction with temporal disturbance regimes are not common. In this study, we assessed patterns of taxonomic composition and diversity within a single large complex river drainage (Colorado River) which was sampled at high spatial resolution and then compared these patterns to those that are present across several major basins that represent different biome types (Neches, Guadalupe, Red, and Rio Grande), but were sampled at lower spatial resolution. Invertebrate and local environmental data were collected in 2021 and 2022, whereas watershed-scale environmental gradient and hydrological data were collected from GIS and flow gages, respectively. Within the single watershed sampled at high spatial resolution, we found that invertebrate composition and site level diversity were mostly driven by local environmental factors, and that beta diversity across sites was largely due to nestedness. Contribution nestedness to beta-diversity was influenced most by variation in hydrological conditions, but the replacement contribution was a function of local conditions. Local-scale diversity across the four watersheds that differed in dominant biome was most driven by local conditions and that beta-diversity was also driven by nestedness. However, across watershed beta-diversity nestedness was driven by local conditions and replacement was most influenced by hydrological characteristics. Overall, our study shows that patterns and interpretation of composition and diversity is spatial-scale dependent, requires an understanding of the relative influence of local- and regional-scale processes that shape communities.