The shape memory effect (SME) under multiaxial pre-deformation has become a significant problem restricting the development of thermo-induced shape memory polyurethane (TSMPU) in complex service conditions. This study experimentally investigates the multiaxial SME of TSMPU under proportionally and non-proportionally multiaxial loadings. The effects of different loading directions and paths with combined tension/compression–torsion pre-deformations on the multiaxial SME are discussed. The results indicate that the SME exhibits significant anisotropic characteristics under different loading angles. Additionally, the multiaxial SME shows considerable dependence on the loading path and loading sequence. The conditions under compression and torsion loadings can promote more deformation recovery than that under tension loading. The functional degradation of the multiaxial SME under various loading paths is revealed through cyclic thermomechanical experiments. Based on these experimental results, the deformation mechanism for the multiaxial SME based on the motivation of molecular chains is proposed, which is crucial for constructing a thermomechanical constitutive model of TSMPU under proportionally and non-proportionally multiaxial pre-deformations.