The southern Sichuan Basin in China holds abundant shale gas resources; however, the shale gas bearing property shows great differences due to the multiple stages of tectonic transformation. The key to revealing the shale gas differential enrichment mechanism is to explore the thermal evolution characteristics during tectonic evolution. Therefore, taking the Luzhou and Changning blocks as an example, which have obvious differences in tectonic evolution, the organic geochemical conditions of Longmaxi shale were firstly compared with the test data. Then, the thermal evolution characteristics under the background differential tectonic uplift-erosion were recovered using basin modeling techniques. The results showed that the two blocks contain similar organic geochemical conditions of the Longmaxi shale. Moreover, the hydrocarbon generation condition in Luzhou Block is greater than that in the Changning Block. Influenced by the differential tectonic evolution, the study area experienced a complex burial history and the formation of multiple unconformities. As a result, the present burial depth of Longmaxi Formation in the Luzhou Block is significantly greater than that in the Changning Block. The thermal evolution history of Longmaxi shale in the study area could be divided into three stages, including a low-temperature stage from Caledonian to Hercynian, a middle-temperature stage from Hercynian to Indosinian, and a high-temperature stage from Yanshanian to Himalayan. In addition, it was found that the Himalayan period is the main stage resulting in the differential gas bearing property of Longmaxi shale in the southern Sichuan area. Under the differential structural modification, the peak time of hydrocarbon generation in the Luzhou Block occurred earlier and the conversion rate was slightly higher than that in the Changning Block.