<p>Karst regions contain large deposits of carbonate rocks, which can be dissolved by groundwater to form sinkholes and caves. This dissolution can have a compounding effect on dynamic loads and thus must be considered in fatigue analysis for construction and engineering projects in such regions. In this study, a self-developed rock dynamics–water pressure–dissolution test system was used to conduct both dissolution tests and cyclic load tests on carbonate rocks to investigate their fatigue characteristics and damage evolution law with different dissolution effects. The results showed that the rock samples sustained different degrees of damage depending on the environmental conditions. Relational expressions between the fatigue strength, fatigue life, elastic modulus, and dissolution rate were fitted to the results to establish an equation for the evolution of fatigue damage under different dissolution actions. The established equation can be used to predict the damage evolution under the combined effects of dissolution and cyclic loads to improve the safety and stability of construction and engineering projects in karst regions.</p><p></p>