Purpose <p>Rhizospheric metabolites play a vital role in the interactions between invasive plants and soil microbes. However, little is known about the metabolites and their co-occurrence patterns with microbial communities in the rhizosphere soil of <i>Amaranthus palmeri S. Watson</i>.</p> Methods <p>In this study, high-throughput sequencing and metabolomics techniques were employed to investigate the diversity and composition of the microbial community, metabolic features, as well as the interaction between microbial genera and environmental factors (differential metabolites and soil physicochemical properties).</p> Results <p>The rhizosphere effect significantly increased microbial alpha diversity (Chao1 index) and reshaped the composition of microbial communities. Notably, some bacterial genera and saprotrophic fungi associated with carbon and nitrogen cycling were more abundant in the rhizosphere soil. Additionally, some pathotrophic fungi exhibited markedly higher abundance in the rhizosphere of <i>A</i>. <i>palmeri</i>. Soil metabolome expression and metabolic pathways were also significantly altered, with the most significant alterations in some fatty acids and lipids. Correlation analysis showed soil pH and ammonium nitrogen content had a considerable impact on the differential phyla and microbial communities. Moreover, co-occurrence network analysis revealed the differential metabolites including LPE(14:0), Pentadecanoic acid, and 18.beta.-Glycyrrhetinic acid, exhibited the strongest associations with keystone microbial genera in the rhizosphere soil of <i>A</i>. <i>palmeri</i>.</p> Conclusions <p>This study demonstrated that differential metabolites were more closely associated with microbial communities than with physicochemical properties in the rhizosphere soil of <i>A</i>. <i>palmeri</i>, providing new insights into the plant-microbe interactions in the invasive ecosystem.</p>