Panax ginseng roots, including the steamed roots, have been demonstrated to possess anticancer properties. However, there have been limited published studies on the cancer preventive effects of American ginseng. In this study, the in vitro and in vivo anti-colorectal cancer effects of American ginseng berry extracts, and their representative bioactive compounds were evaluated. The ginsenoside content in unsteamed American ginseng berry extract (AGE) and steamed berry extract (S-AGE) were determined by HPLC. In comparison to AGE, S-AGE showed significantly stronger antiproliferative effects on HCT-116, SW-480 and HT-29 human colorectal cancer cells. Antiproliferative effects of representative constituents in AGE and S-AGE, ginsenosides Rb3 and Rg3, were also evaluated, showing that Rg3 had a positive effect. Using flow cytometric analyses, we found that S-AGE arrests cancer cells in G1-phase and significantly induces cell apoptosis. Using xenograft mice, we conducted an in vivo antitumor study using S-AGE after HCT-116 cell inoculation. We observed that 50 mg/kg of S-AGE showed significant antitumor effects. Our results suggested that S-AGE inhibited the colorectal cancer growth both in vitro and in vivo, and this inhibition might be achieved through cell cycle arrest and induced apoptosis in the cells.