Considerable debate remains regarding the mechanisms responsible for the reduction in organic matter (OM) pores in post-mature shales. To address this issue, complementary techniques including scanning electron microscopy (SEM), total organic carbon (TOC) analysis, and helium porosity measurement were employed to characterize the microstructure and porosity of post-mature shales from the Qiongzhusi Formation in the southwestern Upper Yangtze region, China. The results show that OM pores in these shales are poorly developed and exhibit highly irregular morphologies. Notably, the degree of OM pore development is negatively correlated with TOC. Interestingly, in samples with TOC < 2.5 wt.%, well-preserved spongy migrated OM is still observable under SEM. The average porosity of Qiongzhusi mudstones is 1.8%; siltstone samples with TOC < 2 wt.% yield an average porosity of 3.5%, whereas samples with TOC > 4 wt.% have an average porosity of only 1.9%. These findings do not support the hypothesis that graphitization causes the significant destruction of OM pores in post-mature shales. Instead, we propose that compaction has been the dominant factor controlling OM pore destruction. Accordingly, we introduce a “depth window” for the development of high-quality shale gas reservoirs: Beyond a certain maximum paleoburial depth, compaction leads to extensive OM pore destruction and a marked decline in reservoir quality. This study advances our understanding of pore evolution in post-mature shales and provides practical guidance for shale gas exploration.