To ensure the imaging quality of the off-axis three-mirror space telescope during the ground adjustment and on-orbit adjustment stages, we reveal the coupling characteristics of the effect of the axial misalignment and the lateral misalignment on aberration based on the Nodal aberration theory from the internal mechanism level. This paper focuses on the compensation relationship generated by the coupling characteristics of two types of misalignments: (1) axial misalignment compensates for lateral misalignment, which reveals a type of working condition where the system image quality may be at a local extreme during the alignment process on the ground; (2) lateral misalignment compensates for axial misalignment. A compensation strategy wherein astigmatisms and comas introduced by in orbit lateral misalignment can compensate for astigmatisms and comas induced by axial misalignment is proposed (defocus cannot be corrected). Taking the off-axis three-mirror system in the laboratory as an example, the accuracy of the analytical relationships can be verified. Simulations and experiments have proven that the imaging quality of the system may reach the diffraction limit (1/14λ), but the system’s image quality is at a local minimum in the presence of both axial and lateral misalignment. When the telescope is misaligned in orbit and the defocus is small, the system image quality can be corrected by properly aligning the lateral misalignment first. The RMS wavefront error after compensation changes less than 0.02λ compared with the design state (the best state of installation and alignment).