Oxygen isotope sclerochronology with mollusk shells can provide vital environmental and ecologic information, but is complicated in regulated, subtropical rivers by irregular river water δ18O and consequently irregular shell δ18O patterns. We performed multi-proxy analyses (δ18O, δ13C, clumped isotopes) from serially-sampled freshwater mussels in two specimens each of Amblema plicata and Cyrtonaias tampicoensis from the Brazos River, Texas to age specimens and test whether they accurately record environmental conditions such as river discharge and water source. Oxygen isotopic measurements are similar to predicted aragonite δ18O values based on temperature and water δ18O, but the record is complex and irregular. To better resolve the chronologies, we performed clumped isotope analyses on select shell intervals. Clumped isotope temperatures (T(Δ47)) ranged from 19° to 36 °C. Summer T(Δ47) values were 3–5 °C higher than measured temperatures, suggesting an offset in paleothermometer calibration. Chronologies based on Δ47 and δ18O reveal specimen ages of 3–4 years and winter growth cessation (or dramatic slowing) in both C. tampicoensis and A. plicata, highlighting thermal limitations on growth and potential biases in environmental reconstructions. Compared with modern shells, historical shells collected before intensive damming showed lower δ18O values yet similar clumped temperatures, suggesting enhanced evaporation in modern river water due to impoundment and/or the 2011–12 drought.Carbon isotope trends were similar between conspecific shells, but differed between species, with substantially higher average values for A. plicata shells (−9‰) than C. tampicoensis shells (−12‰). The correlation between shell δ13C values and the release of 13C-enriched waters from upstream reservoirs demonstrates that δ13C can be used as a proxy for dam release in regulated rivers.