Elevated concentrations of potassium (K) often occur in effluents from wastewater treatment plants, oil and gas production operations, mineral extraction processes, and from other anthropogenic sources. Previous studies have demonstrated that freshwater mussels are highly sensitive to K in acute and chronic exposures, and acute toxicity of K decreases with increasing water hardness. However, little is known about the influence of hardness on the chronic toxicity of K. The objective of this study was to evaluate the chronic toxicity of K (tested as KCl) to a commonly tested unionid mussel (fatmucket, Lampsilis siliquoidea) at five hardness levels (25, 50, 100, 200, 300 mg/L as CaCO₃) representing most surface waters in the United States. Chronic 28-d K toxicity tests were conducted with 3-week-old juvenile fatmucket in the five hardness waters using an ASTM standard method. The maximum acceptable toxicant concentrations (geometric mean of the no-observed-effect concentration and the lowest-observed-effect concentration) increased from 15.1 to 69.3 mg K/L for survival and from 15.1 to 35.8 mg K/L for growth (length and dry weight) and biomass when water hardness was increased from 25 mg/L (soft) to 300 mg/L (very hard). These results provided evidence to support water hardness influence on chronic K toxicity to juvenile fatmucket. However, the chronic effect concentrations based on the more sensitive endpoint (growth or biomass) increased only 2.4-fold from the soft water to the very hard water, indicating that water hardness had limited influence on the chronic toxicity of K to the mussels. These results can be used to establish chronic toxicity thresholds for K across a broad range of water hardness and to derive environmental guideline values for K to protect freshwater mussels and other organisms.