American ginseng (Panax quinquefolius) is one of the most commonly used herbal medicines in the world. Discriminating between P. quinquefolius grown in different countries is difficult using traditional quantitation methods. In this study, a liquid chromatographic mass spectrometry fingerprint combined with chemometric analysis was established to discriminate between American ginseng grown in the USA and China. Fifteen American ginseng samples grown in Wisconsin and 25 samples grown in China were used. The chromatographic fingerprints, representing the chemical compositions of the samples, made it possible to distinguish samples from the two locations. In addition, it was found that some ginsenosides varied widely from P. quinquefolius cultivated in these two countries. P. quinquefolius grown in the USA is higher in ginsenoside R(c), ginsenoside R(d), quinquenoside III/pseudo-ginsenoside RC₁, malonyl ginsenoside R(b1), and ginsenoside R(b2), but lower in ginsenoside R(b1) compared with P. quinquefolius grown in China. These ginsenosides may be responsible for the class separation seen using fingerprinting and chemometric approaches.