American ginseng (Panax quinquefolius) growth is often hampered by replant problem, and the longerm impacts of crop rotation on plant performance remain unclear. In this study, we investigated the alteration of soil nutrients, autotoxic phenolic acids, and fungal communities in American ginseng-cultivated soil after maize growth to establish an American ginseng-maize-American ginseng rotation system in Northern China. Soil nutrient levels were assessed in treatment soils using chemical analytical methods. Autotoxic phenolic acids were determined by HPLC. The fungal community was evaluated by T-RFLP analysis. The effects of rotation on replanted American ginseng growth were measured using a pot experiment. Soil nutrients of maize growth for three to five years (4G-3M, 4G-5M) on American ginseng-cultivated soil (4G) were grouped together with maize-cultivated soil (CM). Syringic acid, ferulic acid, salicylic acid, p-coumaric acid, and total phenolic acids contents in 4G soil were significantly decreased to CM level after one year of rotation (4G-1M)(P < 0.05). Soils supporting maize growth for 5 years (4G-5M) showed a recovery in Simpson diversity and Pielou evenness. Root yield and lateral root numbers of American ginseng increased in 4G-1M soil while root disease severity was significantly lower after 3 year of rotation (4G-3M) (P < 0.05). Multi-linear regression showed that seedling survival rate, root yield, and root disease severity were related to scertain soil chemical and microbial properties while soil microbial properties were rimpacted by soil chemical properties. In summary, maize rotation improved the physicochemical and biological properties of American ginseng-cultivated soil, and these positive effects lasted for at least three years.