Under traffic loading, the soil elements in subgrade are subjected to a complex 3D stress path. To investigate the cyclic behavior of desert subgrade under initial shear stress conditions, the number of cyclic true triaxial tests were implemented on aeolian sand from the Tengger Desert. A large range of initial shear stress levels and different cyclic stress paths (various combinations of cyclic major and intermediate principal stresses) were designed in the experiments. The results show that the initial shear stress level significantly influences the cyclic response, and the response mode of aeolian sand under initial shear stress is incremental failure and elastic shakedown, while it is critical failure without initial shear stress. With the increase in initial shear stress, the permanent strain increases first and then decreases, with the maximum permanent strain occurring at q0 = 50 kPa. Moreover, by comparing the test data under different cyclic stress paths, it is found that the cyclic resistance decreases with the increase in the coefficient of cyclic intermediate principal stress bcyc. Compared to the limiting pore pressure criterion, the conventional 5% axial strain failure criterion may overestimate the cyclic resistance, leading to unsafe evaluation and design. Therefore, by using the pore pressure criterion, the relationship between the limit pore pressure ratio and the initial stress condition was investigated and it was found that the limit pore pressure ratio decreased linearly when the initial shear stress increased.