There is still a lack of systematic understanding of the evolution process of Lianzhou Basin since the Mesozoic and its response to karstic development law (Objective). Based on the comprehensive analysis of the latest field geological investigation, hydrogeological drilling, dissolution experiment, and three-dimensional geological modeling, the tectonic evolution stages of the basin can be divided and karstification of each stage is discussed by considering the existing geological data (Methods). Before the Cretaceous, carbonate rocks with strong dissolution were successively deposited under the rise or fall movement of the crust, which laid a material foundation for karstic development. The Indosinian movement caused vertical multilayered strata to form an EW-trending structure, and Yanshanian movement made the straddle-oblique superimposed NE-SW-trending structure. They controlled the geological structures, spatial distribution characteristics, and dissolution behaviors of carbonate rocks, the distribution of mountains and water systems was established. However, karst was generally not developed. Intracontinental and intermountain faulted confluence lake basin was formed from the Cretaceous to Paleogene, the slow crustal uplift strengthened the karstification around the basin, and it retains the early karst platform now. Later, they were buried-filled-consolidated by alluvial deposits, therefore, karst basically stopped developing, generating a thick-covered red strata basin. Since the Neogene, the rapid uplift of crust leads to the continuous elevation of mountains around the basin, deepening of rivers, and strong development of karst, shaping multilevel karst platforms. When part of Cretaceous red strata in the basin are denuded or cut through, the karstification is reactivated. After many changes and penetrations of water systems, the Quaternary shallow covered karst fault basin is formed (Results). Tectonic evolution controls karstic development, karstification influences internal structure of the basin, soil structure breeds karst ground collapse (Conclusion). This study can provide a scientific basis and guidance for comprehension of karst collapse conditions in covered karst areas.