The crack propagation evolution of carbonaceous mudstone under the action of dry-wet cycles is an important cause of the unstable failure of this type of slope. This paper attempts to reveal the evolution mechanism of mesocrack and macrocrack propagation in carbonaceous mudstone under the action of dry-wet cycles from chemical, physical, and mechanical perspectives. Firstly, the soaking solution of carbonaceous mudstone during the dry-wet cycles was extracted for an ion concentration test to analyze the chemical reactions of carbonaceous mudstone. Then, CT scans were performed on the carbonaceous mudstone samples to study the changing pattern of mesostructure of carbonaceous mudstone during the dry-wet cycles. In the end, the mechanical properties and failure characteristics of carbonaceous mudstone after dry-wet cycles were studied by triaxial compression tests. The results showed that chemical reactions such as calcite dissolution, potassium feldspar hydrolysis, and sodium feldspar hydrolysis occurred during the dry-wet cycle of carbonaceous mudstone. Affected by the dry-wet cycles, the mesostructure of the carbonaceous mudstone gradually changed from face-face contact and edge-face contact to edge-corner contact and corner-corner contact, and the interlayer flake structure was opened and was locally curled and fractured. With the increase in the number of dry-wet cycles, the failure characteristic of carbonaceous mudstone transformed from tensile failure to shear failure, the failure surface of carbonaceous mudstone was deflected from 90° to 60°, and the crack propagation path of carbonaceous mudstone became more complicated. The chemical reaction of carbonaceous mudstone minerals during the dry-wet cycle is an important reason for the initiation and development of pores. The dry-wet cycle aggregates the propagation of mesocracks and structural disorder, transforming the uniform stress state of the rock mesostructure to the concentrated stress state, which is the important reason for the macrocrack propagation evolution of carbonaceous mudstone.