Panxian ham, a traditional Chinese dry-cured ham, is protected by national geographical indication. Similar to other fermented foods, the microbial population of dry-cured ham is pivotal to taste and flavor formation. This study aimed to establish the relationship between microorganisms and metabolites during the spontaneous fermentation of Panxian ham. Multivariate analysis based on metabolomics data revealed that continuous metabolic changes occurred during the entire fermentation process, with the most significant changes occurring in the initial stage of ripening. Thirty-one significantly different metabolites (SDMs) were identified as discriminant factor, and pathway analysis suggested that these metabolites were involved in 30 pathways, including alanine, aspartate, and glutamate metabolism; glycine, serine, and threonine metabolism; and arginine and proline metabolism. Microbial community analysis using the Illumina MiSeq platform indicated that the bacterial community was more complex than the fungal community, and their succession regulation differed during processing. At the genus level, 11 bacteria and five fungi were identified as core microbes, of which was the dominant bacteria and and were the dominant fungi. Further, statistical redundancy analysis (RDA) indicated that , , and promoted the production of amino and fatty acids; and were associated with sugar metabolism, and , , and were closely related with organic acids. These findings provide fundamental knowledge regarding the metabolically active microorganisms in Panxian ham, helping industrial processors to develop effective strategies for standardizing quality parameters.