Streamflow, geomorphology, and network structure play vital roles in the evolution, distribution, and abundances of aquatic species. In the southeastern U.S., where aquatic diversity is high and many species are imperiled, understanding how populations respond to environmental variability across spatial and temporal scales is essential for effective conservation of stream ecosystems and biodiversity. However, linking components of the streamflow regime, considered a master variable driving many biotic and ecosystem processes, to population processes has remained challenging because of methodological and conceptual constraints. This collection of studies uses a range of methods and scales for understanding population responses to streamflow and geomorphic characteristics to help inform management and conservation of stream fishes in the Piedmont province of the southeastern U.S. Specifically; I focus on linking demographic processes (i.e., abundance, survival, recruitment, dispersal, gene flow) to streamflow, geomorphology, and network characteristics. Results of a five-year study show resilient to flow reductions in fluvial-dependent darter species (Etheostoma inscriptum) population in a middle order Piedmont river, with high recruitment and local survival during severe and prolonged drought. Additionally, field observations and model results for five species in a suite of Piedmont streams indicate that fish population responses to low- and high-flow events vary with stream size and proximity to larger stream segments. This suggests that stream network characteristics influence the ability for populations to remain stable in response to variable streamflows. Lastly, a population geneticsanalysis of a small-stream cyprinid indicates that populations in close proximity to a river mainstem are well interconnected with substantial gene flow, and likely provide colonizers to smaller stream tributaries that are more vulnerable to local extirpations. Additionally, geomorphic features, as well as dams, likely influence the stepping-stone model of dispersal for this cyprinid. Collective results from this dissertation show that fish populations in larger tributaries are more resilient to changes in streamflow compared to populations in smaller tributaries, and that stream size, geomorphic context, and network position are important factors to include when predicting the biological effects of flow alterations across a watershed to inform management decisions.