Plant-microbe interactions can modulate the plant metabolome, but there is no information about how different soil microbiomes could affect the sugarcane metabolome and its quality. Here, we collected soil and stalk samples from bitter sugarcane (BS) and sweet sugarcane (SS) to conduct chemical analysis, microbiome and metabolome analysis. Our data revealed lower species diversity in the BS group than in the SS group, and 18 discriminatory OTUs (relative abundance ≥ 0.01%) were identified. Sugarcane metabolomic analysis indicated the different abundances of 247 metabolites between the two groups in which 22 distinct metabolites involved in two flavonoid biosynthesis pathways were revealed. Integrated analysis between soil microbial taxa, stalk chemical components, and soil properties showed that the flavonoid content in stalks and the nitrogen concentration in soil were highly correlated with the soil microbiome composition. Bacteria at the genus level exhibited greater associations with distinct metabolites, and six genera were independently associated with 90.9% of the sugarcane metabolites that play a major metabolic role in sugarcane. In conclusion, this study provided evidences that the interaction between plant-microbiome can change the plant metabolome.