Calcium (Ca) is necessary for plant growth and stress resistance, which are essential for the successful cultivation of Panax quinquefolium L. (American ginseng). However, information about the physiology of Ca nutrition in this species is limited. Therefore, the objective of this study was to determine the effect of Ca on the growth and physiological performance of American ginseng. Two-year-old American ginseng plants were supplemented with the following Ca concentrations [Ca2+] in a hydroponic system: 0, 160.17, 320.34, 640.68, and 961.02 mg⋅L−1. Measurements included growth biomass accumulation, chlorophyll (Chl) content and fluorescence, photosynthetic parameters, antioxidant enzyme activity, root activity, and malondialdehyde content. Biomass, stem height, leaf area, maximum photochemical efficiency, and superoxide dismutase activity peaked at [Ca2+] of 640.68 mg⋅L−1. Actual photochemical efficiency, minimum saturating irradiance, photosynthetic rate, catalase and peroxidase activities, and root activity reached their maximum at [Ca2+] of 320.34 mg⋅L−1. Stem diameter and regulated thermal energy dissipation increased with [Ca2+]. The sum of nonregulated heat dissipation and fluorescence emission and malondialdehyde content decreased to a minimum at [Ca2+] of 320.34 mg⋅L−1. The Chl content reached a maximum at [Ca2+] of 160.17 mg⋅L−1, but the Chl a/b ratio increased with [Ca2+]; the actual photochemical efficiency and photosynthetic rate reached their maximum level at Chl a/b ratios of 2.04 and [Ca2+] of 320.34 mg⋅L−1. Therefore, the optimal [Ca2+] for American ginseng growth was 320.34 mg⋅L−1. Furthermore, an appropriate increase [Ca2+] in the growth medium may improve biomass accumulation, light energy utilization efficiency, and stress resistance in American ginseng.