The purpose of this study was to determine whether water quality parameters commonly associated with primary productivity may be used to predict the susceptibility of a specific water body to exceed proposed fish consumption advisory limitation of 0.3 mg kg⁻¹. South Dakota currently has nine lakes and impoundments that exceed fish tissue mercury advisory limits of 1.0 mg kg⁻¹ total mercury, far exceeding US Environmental Protection Agency and Food and Drug Administration 0.3 mg kg⁻¹ consumption criteria. Previous studies suggest that increased aquatic productivity may mitigate the effects of biological production and subsequent uptake of methyl mercury through bio-dilution; however, it is uncertain whether these trends may exist within highly alkaline and highly productive aquatic conditions common to South Dakota lakes and impoundments. Water quality parameters and fish tissue mercury data for northern pike and walleye were collected and assessed using existing South Dakota Department of Environment and Natural Resources and Game Fish and Parks data. The data was initially screened using both parametric linear regression and non-parametric Mann–Whitney rank sum comparisons and further assessed using binary logistic regression and stepwise logistic regression methodology. Three separate phosphorus measurements (total, total dissolved, and Trophic State Index) and pH were determined to significantly correlate with increased mercury concentrations for the northern pike-in-impoundments model. However, phosphorus surprisingly was not a strong predictor for the remaining scenarios modeled. For the northern pike-in-natural lakes models, alkalinity was the most significant water quality parameter predicting increased mercury concentrations. Mercury concentrations for the walleye-in-natural lakes models were further influenced by pH and alkalinity. The water quality and fish tissue mercury interrelationships determined within this study suggest aquatic productivity, and consequential eutrophication processes appear to be reasonable indicators of fish tissue mercury susceptibility for aquatic conditions common to South Dakota and highlight the continuing need to minimize eutrophication through effective watershed management strategies.