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??atm) displayed higher growth and survival than individuals grown at both lower (250??atm) and higher pCO2 levels (750 and 1500??atm). 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??atm 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.