Unknown causes behind the loss of freshwater mussel populations have prompted population restoration as a tool to recover these imperiled species. However, water quality conditions that support mussel species within natural environments and potential causes of water quality impairment in systems with declining populations are typically unknown and may be critical knowledge needed before reintroducing mussels. Our objective was to relate the growth and survival of declining freshwater mussel populations of the Brook Floater Alasmidonta varicosa (Lamarck, 1819) to water quality parameters within 4 Massachusetts, USA, rivers containing extant populations. We deployed propagated age-1 and age-2 Brook Floater in contained systems (silos) for 1 growing season (June–October). Through biweekly sampling, we tracked the growth and survival of mussels then modeled their relationships with water quality variables. Mussels had a higher growth rate at a higher chlorophyll a (Chl a) value (2.82 µg/L) over the temperature range measured (biweekly mean = 16–26°C) when compared with lower Chl a values (0.61 and 1.17 µg/L). Age-1 mussel growth rate was negatively affected by low Chl a concentration (0.61 µg/L) across the temperature range, but age-2 mussel growth rate was not negatively affected until temperatures were above ~22°C. Na⁺ limited the growth rate of mussels, with the rate of change in growth rate for age-1 mussels greater than for age-2 mussels. Other cations (Mg²⁺, K⁺, and Ca²⁺)—potentially linked to road deicers—also negatively affected growth rate in all 4 rivers but may have had a greater impact on mussels in rivers with reduced growth rates from lower temperatures and Chl a. However, survival was uniformly high across all rivers, indicating water quality parameters may have sublethal but not lethal effects. Additional assessments for chronic water quality stressors along with changing land cover, land management, and climates are important considerations for restoration potential and the long-term persistence of populations.