Fritillaria cirrhosa is an important cash crop, and its industrial development is being hampered by continuous cropping obstacles, but the composition and changes of rhizosphere soil microorganisms and metabolites in the cultivation process of Fritillaria cirrhosa have not been revealed. We used metagenomics sequencing to analyze the changes of the microbiome in rhizosphere soil during a three-year cultivation process, and combined it with LC-MS/MS to detect the changes of metabolites. Results indicate that during the cultivation of Fritillaria cirrhosa, the composition and structure of the rhizosphere soil microbial community changed significantly, especially regarding the relative abundance of some beneficial bacteria. The abundance of Bradyrhizobium decreased from 7.04% in the first year to about 5% in the second and third years; the relative abundance of Pseudomonas also decreased from 6.20% in the first year to 2.22% in the third year; and the relative abundance of Lysobacter decreased significantly from more than 4% in the first two years of cultivation to 1.01% in the third year of cultivation. However, the relative abundance of some harmful fungi has significantly increased, such as Botrytis, which increased significantly from less than 3% in the first two years to 7.93% in the third year, and Talaromyces fungi, which were almost non-existent in the first two years of cultivation, significantly increased to 3.43% in the third year of cultivation. The composition and structure of Fritillaria cirrhosa rhizosphere metabolites also changed significantly, the most important of which were carbohydrates represented by sucrose (48.00–9.36–10.07%) and some amino acid compounds related to continuous cropping obstacles. Co-occurrence analysis showed that there was a significant correlation between differential microorganisms and differential metabolites, but Procrustes analysis showed that the relationship between bacteria and metabolites was closer than that between fungi and metabolites. In general, in the process of Fritillaria cirrhosa cultivation, the beneficial bacteria in the rhizosphere decreased, the harmful bacteria increased, and the relative abundance of carbohydrate and amino acid compounds related to continuous cropping obstacles changed significantly. There is a significant correlation between microorganisms and metabolites, and the shaping of the Fritillaria cirrhosa rhizosphere’s microecology by bacteria is more relevant.