American ginseng (Panax quinquefolius L.) is an important cash crop, but long-term monoculture often results in serious root rot disease and yield reduction. The dynamics of soil phenolic acids perform an important function in soil microbe–plant interactions, but the extent to which changes in phenolic acids that occur under the continuous monoculture of American ginseng influence growth and the rhizosphere microbial community are unclear. In this study, American ginseng was planted in soil that had been used for 3 years of continuous monoculture (3 yr) and into a soil with no history of planting American ginseng (0 yr). Soil phenolic acids, rhizosphere microbiome characteristics, and pathogen suppression were analyzed. In the findings, the diversity and structure of the rhizosphere microbial community were affected by monoculture history, as the diversity of fungi and bacteria in 3 yr soil was higher than in 0 yr soil. The physiological performance of American ginseng in 3 yr soil was significantly lower than that in 0 yr soil. Soil phenolic acid contents decreased with the longer monoculture history, and high concentrations of phenolic acids suppressed the growth of American ginseng-specific pathogens. Soil phenolic acids appeared to modulate the pathogen population and the rhizosphere microbiome in American ginseng monocultures.