No systematic comparative study has been conducted on the factors controlling organic matter enrichment in the different depositional environments of the Lower Cambrian Qiongzhusi Formation in the western Middle Yangtze Block, leading to a large discrepancy in our understanding. Based on organic geochemical and elemental analyses of core, outcrop, rock, and mineral samples from the slope, deep-water shelf, and shallow-water shelf, in this study, comparative analysis of the organic matter content, sedimentological characteristics, and depositional paleoenvironments of the Lower Cambrian Qiongzhusi Formation in the western Middle Yangtze Block was conducted, and the main controlling factors and models of the organic matter enrichment were investigated. The results revealed that the organic matter enrichment in the Qiongzhusi Formation was jointly controlled by redox conditions, water restriction, upwelling currents, terrigenous inputs, and paleo-productivity, but the main factors controlling the enrichment during the different periods were significantly different. (1) During the deposition of the Qiong 1 Member, the extensional rifting was strong, and the sea level was always high. The low degree of terrigenous dilution and anoxic conditions favored organic matter preservation. In this period, the upwelling currents were the main factor controlling organic matter enrichment. The paleo-productivity decreased as the intensity of the upwelling currents gradually weakened from the slope to the shelf, leading to a decrease in the total organic carbon (TOC) content and thereby a gradual decrease in the biogenic silica content of the shale. (2) During the deposition of the Qiong 2 Member, the extensional rifting weakened, and the sea level continued to drop. The upwelling currents, terrigenous input, and redox conditions were all important factors controlling the organic matter enrichment in the region. From the slope to the shelves, the conditions favorable for organic matter enrichment gradually worsened, and the TOC content gradually decreased, with the lithofacies gradually transitioning from biogenic siliceous shale to clayey shale or clayey-calcareous shale. (3) During the deposition of the Qiong 3 Member, the Yangzi Platform underwent a filling and leveling-up process, and the redox conditions played a major role in controlling the organic matter enrichment. The entire region was dominated by an oxygen-rich environment, and the conditions were no longer favorable for organic matter preservation, leading to a low average TOC content. Overall, the spatial variability of the TOC content was closely associated with changes in the depositional paleoenvironment caused by sea-level changes.