Estimates of historical variability in river ecosystems are often lacking, but long-lived freshwater mussels could provide unique opportunities to understand past conditions in these environments. We applied dendrochronology techniques to quantify historical variability in growth-increment widths in valves (shells) of western pearlshell freshwater mussels (Margaritifera falcata). A total of 3 growth-increment chronologies, spanning 19 to 26 y in length, were developed. Growth was highly synchronous among individuals within each site, and to a lesser extent, chronologies were synchronous among sites. All 3 chronologies negatively related to instrumental records of stream discharge, while correlations with measures of water temperature were consistently positive but weaker. A reconstruction of stream discharge was performed using linear regressions based on a mussel growth chronology and the regional Palmer Drought Severity Index (PDSI). Models based on mussel growth and PDSI yielded similar coefficients of prediction (R²_Pred) of 0.73 and 0.77, respectively, for predicting out-of-sample observations. From an ecological perspective, we found that mussel chronologies provided a rich source of information for understanding climate impacts. Responses of mussels to changes in climate and stream ecosystems can be very site- and process-specific, underscoring the complex nature of biotic responses to climate change and the need to understand both regional and local processes in projecting climate impacts on freshwater species.