Laboratory toxicity tests are a standard tool for evaluating the potential impairment of freshwater systems by anthropogenic activities. Although these controlled assays yield valuable information about individual stressors, it remains uncertain whether they accurately reflect community-level impacts on aquatic organisms in natural environments. We present a unique, decades-long dataset combining in-stream toxicity testing and macroinvertebrate community surveys from sites along Bear Creek on the Oak Ridge Reservation (Tennessee, USA), downstream of the Y-12 National Security Complex, allowing us to assess the predictive power of toxicity tests conducted in the lab using stream water for community-level ecological effects. The toxicity testing data set consists of biannual three-brood Ceriodaphnia dubia tests from 2005 to 2025, and significant impacts of the stream water on C. dubia reproduction have been consistently observed at certain sites through time. Analysis of water quality data in conjunction with these responses has revealed that water quality parameters, specific conductance to the greatest extent, have a strong correlation with observed sublethal toxicity to C. dubia (higher conductivity values are correlated with greater toxicity). We identified trends in macroinvertebrate communities, both community-level diversity metrics and family-level presence/absence and densities, that significantly correlated with conductivity and sublethal toxicity responses of C. dubia to Bear Creek water samples collected at the same sites during the same period. We found that Ephemeroptera, Plecoptera, Trichoptera (EPT), and non-EPT species density and richness had significant relationships with C. dubia reproduction as percent of control (greater toxicity observed in the lab correlated with decreased invertebrate diversity), indicating that toxicity signals measured in the lab have a significant relationship with instream communities. At the family level, we found that many pollution-tolerant families were present and at higher densities during periods of sublethal toxicity, as measured by percent control reproduction of C. dubia in the lab, while some sensitive families were absent and/or at lower densities during these periods. These extensive, multi-decadal data sets allow us to investigate the potential for laboratory toxicity tests to detect changes in water quality that impact the diversity of aquatic communities in the field.