Stream ecosystems are profoundly degraded by watershed urbanization. Hydrologic, geomorphic, chemical and thermal adjustment following urban development contributes to substantial biodiversity loss in impacted streams. However, the extent of degradation along an urban gradient may not be uniform among regions. The hydrogeologic and climatic setting in which a stream is located may influence the severity of abiotic and biotic impact induced by urban development. I explored and compared differences in stream ecosystem responses to urbanization between the Coastal Plain and Piedmont physiographic regions of the eastern United States. Taxon-specific responses of fishes and macroinvertebrates as well as the coherence of benthic invertebrate communities along gradients of landscape stressors were quantified. Hydrologic, chemical and thermal impact induced by watershed urbanization was compared between the two physiographic provinces using existent large datasets collected by various governmental entities. I also compared the severity geomorphic and sediment regime alteration in urban streams between regions using direct measurements of channel morphometry and in situ natural experiments within selected watersheds. Biotic sensitivity to urbanization was consistently found to be heightened in Piedmont streams relative to those in the Coastal Plain. Such trends were consistently observed for fish and macroinvertebrate taxa as well as for invertebrate community coherence. The most tolerant macroinvertebrate communities were associated with low channel slopes, effective soil permeability and high levels of wetland cover. Rural Coastal Plain streams exhibited fewer flood events that were longer in duration; however, flood hydrology was more impacted by urbanization in Coastal Plain streams relative to those of the Piedmont. Conversely, thermal impact induced by urbanization was greater in Piedmont streams. Experimental observations concluded that benthic sediment size structure, deposition and transport were more impacted by urban development in Piedmont streams relative to those of the Coastal Plain. My findings highlight interregional heterogeneity in stream ecosystem responses to landscape change, suggesting that effective watershed management decisions may need to consider the physiographic setting in order to improve efficacy. Furthermore, results suggest that watersheds characteristic of hydrogeomorphic attributes that effectively transfer water to channels during precipitation events may be acutely vulnerable to urban development.