To investigate the mechanical properties of high liquid limit clay under different humidity and stress levels in hot and humid regions, high liquid limit clay in hot and humid regions was studied. Dynamic and static triaxial tests were carried out under different humidity and stress levels to reveal the stress-strain relationship and permanent deformation properties across different water contents and confining pressures. The results show that under low confining pressures of the subgrade, the stress-strain curves of the specimens exhibit either strain hardening or strain stabilization, and the failure strength of the specimens decreases with increasing water content and decreasing confining pressure. Based on the Konder hyperbolic model, the stress-strain relationship obtained from the static triaxial test was normalized, and a stress-strain equation for high liquid limit clay was established that simultaneously considered the effects of both water content and confining pressure. The permanent deformation of the specimen increased with the increase in the deviatoric stress, which was inversely correlated with the confining pressure, and the ability of the specimens to resist permanent deformation decreased under wetting effects. Based on the dynamic and static test results, a mechanical-empirical prediction model was proposed to predict the permanent deformation of subgrade soil by taking into account the shear effect, restraint effect, and damage due to wetting effects. The model featured high prediction accuracy and had been validated using experimental data from other scholars, proving its good applicability.