Principal component analysis (PCA) was used to extract geological information about regional strata and mineralization from many high-quality stream sediment geochemical data in the middle-southern part of the Sanjiang orogenic belt. According to the geological reality, the 32 main ore-forming elements in the study area were grouped into seven element associations that reflected the stratum features and mineralization. The study area was further divided into six geochemical domains that reflected the geological background. The strata and structure were combined with mineral data and revealed that the geological domains proposed in this paper represented the geological background of the study area. The corresponding elements within these geochemical domains have higher concentrations and enrichment factors, showing that the geological domains in the study area are reasonable. In the study area, the observed anomalies in the geochemical domains highlighted effective anomalies and reduced false anomalies. These anomalies can not only be used to identify potential metallogenic areas, but also provide information on tectonics; for instance, the middle axial fault of the Lanping-Simao basin was reflected in the linear anomalies of the LiB element association. The results of this study can help understand the combination and distribution characteristics of ore-forming elements and the regional geological structure of the middle-southern part of the Sanjiang orogenic belt.