The Luzhou area in the southern Sichuan Basin has experienced multiple tectonic movements, forming a complex fault system; the activity has an important impact on the enrichment of shale gas in this area. In order to reveal the influence of the fracture system on the differential enrichment of shale gas, this paper takes the southern Sichuan Basin as the research object. The structural evolution process and fracture development characteristics of the different tectonic units in Luzhou area of southern Sichuan were characterized by conducting a seismic profile analysis, structural recovery using a back-stripping method, and core hand specimen description. We clarified the control effect of the structural deformation and fracture on the differential enrichment of shale gas, and we established a differential enrichment model of shale gas in the Luzhou area. The results show that: (1) The Luzhou area has undergone the transformation of a multi-stage tectonic movement. There are many sets of detachment structures in the longitudinal direction, and the plane structural form is a thin-skin fold-thrust belt composed of wide and narrow anticlines in the north–south direction. (2) The faults in the study area are affected by the Himalayan tectonic movement. The high-angle reverse faults are developed, and the number of large faults is small. The second and third faults are mainly developed. The second faults are only developed at the high position of the structure, which has a significantly destructive effect on shale gas reservoirs, while the third and fourth faults have no significant destructive effect on shale gas reservoirs. (3) In the study area, the types of cracks are categorized into transformational shear cracks, bed-parallel shear cracks, intraformational open cracks, lamellation cracks, shrinkage cracks, and abnormal high-pressure cracks. The thickness of the shale rock mechanical layer, brittle mineral content, and organic matter content jointly control the crack development degree in the shale of the Wufeng–Longmaxi Formation. (4) The uplift erosion, structural deformation, and fracture development caused by the structural evolution have affected the preservation of shale gas, resulting in the differential enrichment of shale gas reservoirs in the region. Based on the enrichment factors of shale gas, we established a differential enrichment model of shale gas in typical structural units and optimized the favorable enrichment areas, which are important contributions for guiding shale gas exploration and development in the Sichuan Basin.