Seawater magnesium (Mg) and calcium (Ca) have undergone secular fluctuations throughout the Phanerozoic, controlling whether the dominant calcium carbonate precipitant is calcite or aragonite + high-Mg calcite. Although these oscillations in seawater Mg/Ca ratios have been implicated as an important control on Phanerozoic diversification of calcifying marine organisms, determining the degree to which Mg/Ca ratios affected different clades requires integration of experimental data with historical patterns of biodiversity from the fossil record. We explore short-term and long-term responses of echinoderms to shifting calcite-aragonite seas by combining experimental and deep-time biodiversity investigations. While experimental results support a strong relationship between Mg/Ca ratios and short-term echinoderm regeneration rates, patterns of Phanerozoic echinoderm diversification dynamics show no correspondence with Mg/Ca ratios or calcite-aragonite sea transitions. This decoupling between short- and long-term responses of echinoderms to seawater Mg/Ca ratios suggests echinoderms were relatively unaffected by seawater chemistry throughout their evolutionary history, possibly due to their ability to alter skeletal Mg fractionation and/or adapt to gradual shifts in seawater chemistry. Notably, our results indicate a strict uniformitarian extrapolation of experimental results over geological time scales may not be appropriate for many calcifying marine invertebrates. Instead, the effect of seawater Mg/Ca ratios should be evaluated for individual clades using both experimental and deep-time biodiversity data in a time series.