The development of hydrogels possessing both excellent self-healing and mechanical properties in hydrogel science due to their tight relationship with the many potential application scopes is of great significance. Herein, a novel class of polyurethane (PU) hydrogels with intermolecular quadruple hydrogen-bonding interactions were designed and fabricated by the copolymerization of poly(ethylene glycol) methacrylate end-capped urethane ether prepolymer (PU-PEGMA) with 2-(3-(6-methyl-4-oxo-1,4-dihydropyrimidin-2-yl)ureido)ethyl methacrylate (SCMHBMA) bearing the 2-ureido-4-pyrimidone (UPy) unit. The effects of the SCMHBMA content on the self-healing behaviors and mechanical properties of the PU hydrogels were investigated. The results indicate that the fabricated PU hydrogels can autonomously and rapidly repair occurring incisions or cracks at ambient temperature without the need for any stimulus and possess high deformability under both tensile and compressive stress and strong recoverability upon removal of stress, thus exhibiting outstanding self-healing, elasticity, robustness and toughness. The presence of UPy units in PU macromolecular chains is a decisive factor endowing the PU hydrogels with these characteristics.