The thrust- nappe structure has remarkable influence on the formation of effective traps and the allocation of source and reservoir systems, and its evolution is of great significance for oil and gas exploration. The thrust- nappe occurred strongly in the southwest margin of the Ordos basin since the Mid- Late Mesozoic, but transformation of its tectonic regime lacks chronological constraint. Thermochronology is a useful method to reveal uplift, exhumation and evolution of mountains and basins. Based on the analysis of bedrock apatite fission tracks drilled in the eastern margin of Qilian Shan and a comprehensive study of thermal history modeling in the southwestern Ordos basin, the spatial- temporal evolution of tectonic regime transformation in the southwest margin of Ordos basin is discussed. The thermal history modeling results indicate that the eastern Qilian Shan rapidly cooled during the Middle Jurassic to Early Cretaceous (ca.174~130 Ma). This uplift event was widespread in the southwest margin of Ordos basin. Combined with the simultaneously strong thrust fold deformation, uplift, exhumation and conglomerate deposition of southwest Ordos basin margin, it indicates that that the southwest Ordos basin margin and the eastern Qilian Shan entered the compressional environment after the Yan’an period in the Middle Jurassic (ca.170 Ma). The deformation and rock uplift and exhumation were enhanced during the Late Jurassic. This compression deformation, characterized by weakening from the west to the interior of the basin, lasted until the early Early Cretaceous, and should be closely related to the north- easterly convergence of the Tethys tectonic domain. At the beginning of the Sanqiao period of the Early Cretaceous, the southwest Ordos margin was in an extensional environment and deposited thick conglomerate of the Liupanshan Group due to the convergence of multiple plates in East Asia. The determination of the spatial- temporal evolution and dynamic background of the Mid- late Mesozoic tectonic regime transformation in the southwest margin of the Ordos basin is of great significance to discuss the formation and evolution of the region and petroleum exploration.