Understanding the factors driving the distribution of unionid freshwater mussels, a highly imperiled group of organisms is fundamental for conservation plans, evaluation of threats, and predicting the impact of climate change. The Colorado River in Texas is prone to both drying and flash flooding, due to its natural flow patterns, climate variability, and human activities. Several studies in this watershed have examined the distribution of mussels at multiple scales and in relation to flow. Fine-scale distribution data collected in spatially extensive surveys in one of the tributaries (San Saba) of this watershed detected differences in community structure between upper and lower river segments and between pools and riffles. Using a HEC-RAS model for the upper segment, site occupancy could be predicted with 67-79 % accuracy based on hydrodynamic conditions at high and low flows and up to 55% of variation in species abundances. Preliminary results of ongoing modeling efforts suggest that pool habitat tends to be more stable across flows in the upper river segment of the San Saba River than in the lower San Saba River, where pools convert to raceways with higher velocities, which may wash mussels out of this habitat. An analysis of historical streamflow and mussel community data from 480 sites throughout the watershed revealed consistent patterns in respect to life history groups across three spatial scales (i.e., sub-basin, mainstem, tributary). These patterns were associated with the flow regime, favoring longer-lived and slower growing species downstream in tributaries and mainstem sites as well as larger sub-basins. This presentation highlights how multiscale approaches and collaborations across disciplines (ecologists and engineers) can provide valuable insights into drivers of spatial patterns of riverine organisms.