Identifying and understanding functional process domains (sensu Montgomery, 1999) in rivers is paramount for linking the physical habitat template to ecosystem structure and function. To date, efforts to do this have been rare, especially in large rivers, as they require appropriate tools for quantifying habitat heterogeneity with fine-scale resolution across broad spatial extents. In this study, we used side-scan sonar technology to map riverbed substrate at six sites in the Yellowstone and Missouri rivers. Substrate maps were then analyzed and visualized using geospatial analysis to relate fine-grained spatial substrate patterns to process domain structure. Our findings revealed two distinct nested domains of substrate patchiness, suggesting that different factors are responsible for shaping patterns of substrate at different scales. Although small-scale patchiness in substrate was likely driven by internal, or autogenic, physical processes, patterns at larger segment extents (>3 km) were often driven by abrupt transitions in habitat related to exogenous factors such as lateral erosion of talus, tributary inputs, and bank armoring. Additionally, we found that heterogeneity in benthic substrate increased with spatial extent at all of our study sites; however, this relationship was lower in the Missouri River, which is altered by impoundment. Our study represents one of the first efforts to relate benthic habitat heterogeneity to nested process domain structure in large riverscapes, and offers a unique perspective for linking landscape processes, geomorphological habitat heterogeneity, and biological structure and function in large rivers.