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Ligusticum chuanxiong Hort. is considered an important medicinal herb with extremely high economic value and medicinal value due to its various effects, including anti-oxidation, sedative action, hepatoprotection, and invigorating blood circulation. However, L. chuanxiong cultivation is hampered by various plant diseases, especially the root rot caused by Fusarium solani, hindering the sustainable development of the L. chuanxiong industry. The occurrence of soil-borne diseases is closely linked to imbalances in the microbial community structure. Here, we studied the yields, rhizosphere microbiota, and soil physiochemical characteristics of healthy and diseased L. chuanxiong plants affected by root rot with high-throughput sequencing and microbial network analysis, aiming to explore the relationships between soil environmental factors, microbiomes, and plant health of L. chuanxiong. According to the results, L. chuanxiong root rot significantly decreased the yields, altered microbial community diversity and composition, enriched more pathogenic fungi, recruited some beneficial bacteria, and reduced microbial interaction network stability. The Mantel test showed that soil organic matter and pH were the major environmental factors modulating plant microbiome assembly. The root rot severity was significantly affected by soil physiochemical properties, including organic matter, cation exchange capacity, available nitrogen, phosphorus, potassium, and pH. Furthermore, two differential microbes that have great potential in the biocontrol of L. chuanxiong root rot were dug out in the obtained results, which were the genera Trichoderma and Bacillus. This study provided a theoretical basis for further studies revealing the microecological mechanism of L. chuanxiong root rot and the ecological prevention and control of L. chuanxiong root rot from a microbial ecology perspective.