Sanchuan ham is appreciated in Yunnan Province, China, for its characteristic flavor and taste, while the microbial community structure and biogenic amines content remain unclear during fermentation processes. In this study, we explored the physicochemical property, biogenic amines concentration and microbial diversity of external and internal Sanchuan ham by high-throughput sequencing during the processing of Sanchuan ham. Results showed that the nitrite remained at a stable level of 0.15 mg/kg which was significantly lower than the national health standard safety level of 20 mg/kg. In addition, compared with fresh hams, the content of total free amino acids in ripe Sanchuan ham has grown 14 folds; sour and bitter were the main tastes of Sanchuan ham. Notably, the concentration of cadaverine was the highest of all biogenic amines during the entire fermentation period. At the bacterial phyla level, Firmicutes and Actinobacteria were the two main phyla, while at the genus level, Staphylococcus was a significant strain throughout the whole fermentation. Moreover, the dry stage has a great impact on the succession change of microbial community structure. Simultaneously, the change trends and composition of bacteria in the interior have slight discrepancies with those of the exterior of Sanchuan ham.