The production of American ginseng (
Panax quinquefolius
L.) is severely limited by the replant disorders in China. Crop rotation with maize might reduce the replant problems, but little information is available on the effect of maize rotation on soil cultivated with ginseng. In this study, we analyzed nutrients, phenolic acids, and microbial communities in soils from the fields with continuous maize, mono-culture ginseng, and 1-, 3-, and 5-year maize rotation after ginseng. Pot experiments were also conducted to evaluate the performance of replanting ginseng in these soils. The results showed that Mn, Cu, and 5 phenolic acids in ginseng-cultivated soil were significantly decreased by maize rotation. A 5-year maize rotation significantly increased the relative abundance of beneficial soil bacteria, such as
Arthrobacter
, rather than decreasing the abundances of potential pathogenic genera. Clustering analysis revealed that the physicochemical properties and microbial communities of 3- and 5-year maize rotation soil were more similar to CM than to G soil. The biomass of replanted ginseng root was improved, and root disease was reduced over 3 years of maize rotation. Overall, the results showed that at least a 3-year maize rotation is needed to overcome the replant failure of American ginseng.