Polyurethane (PU) is a synthetic material available for researchers to be designed in terms of their demands. This study prepared a novel polyurethane thermoplastic elastomer (PUTE) as an asphalt modifier through the reasonable selection of raw materials and formula. The results of the Fourier transform infrared spectroscopy (FTIR) test confirm the chemical reaction between ─ NCO groups in PUTE prepolymer and ─ OH groups in the most polar asphalt molecules (asphaltenic regions). Effects of the PUTE modifications (1%, 3%, 5%, 7%, 9%, 11%, 13%, and 15% by asphalt binder weight) on the asphalt binder properties were then studied through a series of tests. PUTE is demonstrated to play a positive role in high- and low-temperature properties and the mechanical properties of the asphalt binder. All of the PUTE modified binders have desirable storage stability. Moreover, using 11% PUTE is recommended. Finally, the technical properties of PUTE and SBS modified asphalt mixture were compared. The results indicate that the PUTE modified asphalt mixture performs better in low-temperature property and moisture stability than the SBS modified asphalt mixture, whereas the PUTE modified asphalt mixture has worse high-temperature property than the SBS modified asphalt mixture.