Freshwater salinization is a rapidly emerging ecological issue and is correlated with significant declines in aquatic biodiversity. It remains unclear how changing salinity regimes affect the physiology of sensitive aquatic insects, such as mayflies. We used the parthenogenetic mayfly, N. triangulifer, to ask how ionic exposure history alters physiological processes and responses to subsequent major ion exposures. Using radiotracers (²²Na and ³⁵SO₄), we observed that mayflies reared in dilute control water (16 mg L^-1 Na and 23 mg L^-1 SO₄) and subsequently transferred to elevated salinities (153 mg L^-1 Na or 667 mg L^-1 SO₄) had 2-fold (p<0.0001) and 8-fold (p<0.0001) greater ion uptake rates than mayflies chronically reared in elevated Na or SO₄, respectively. Ca transport was uniformly much lower and was minimally influenced by exposure history. With qRT-PCR, we observed that the expression of many ion transporter genes in mayflies was influenced by elevated salinity in an ion-specific manner (upregulation in response to SO₄, downregulation in response to Ca). Elevated Na exposure had minimal influence on the same genes. Finally, we demonstrated that acute NaCl (1850 mg L^-1) toxicity was reduced by 45% in 10-day old mayfly larvae that had been reared in slightly elevated NaCl (481 mg L^-1) compared to control-reared siblings (p<0.01). Similar acclimatory toxicity bioassays are ongoing for Ca and SO₄ challenges. Modest physiological changes in chronic salinity exposure suggest some acclimation, but may not suffice in multistressor conditions common in nature. Overall, this project provides evidence that exposure history to elevated salinity modifies physiological processes (e.g., ion flux and gene expression) and the resultant major ion toxicity in N. triangulifer.