The Eastern oyster, Crassostrea virginica (Gmelin, 1791), is the second most valuable bivalve fishery in the USA and is sensitive to high levels of partial pressure of CO₂ (pCO₂). Here we present experiments that comprehensively examined how the ocean’s past, present and projected (21st and 22nd centuries) CO₂ concentrations impact the growth and physiology of larval stages of C. virginica. Crassostrea virginica larvae grown in present-day pCO₂ concentrations (380 μatm) displayed higher growth and survival than individuals grown at both lower (250 μatm) and higher pCO₂ levels (750 and 1500 μatm). Crassostrea virginica larvae manifested calcification rates, sizes, shell thicknesses, metamorphosis, RNA:DNA ratios and lipid contents that paralleled trends in survival, with maximal values for larvae grown at 380 μatm pCO₂ and reduced performance in higher and lower pCO₂ levels. While some physiological differences among oysters could be attributed to CO₂-induced changes in size or calcification rates, the RNA:DNA ratios at ambient pCO₂ levels were elevated, independent of these factors. Likewise, the lipid contents of individuals exposed to high pCO₂ levels were depressed even when differences in calcification rates were considered. These findings reveal the cascading, interdependent impact that high CO₂ can have on oyster physiology. Crassostrea virginica larvae are significantly more resistant to elevated pCO₂ than other North Atlantic bivalves, such as Mercenaria mercenaria and Argopecten irradians, a finding that may be related to the biogeography and/or evolutionary history of these species and may have important implications for future bivalve restoration and aquaculture efforts.