Wood-plastic composites (WPCs) are sustainable green material with extensive application prospects in both industry and daily life. So a more convenient, environmentally friendly and effective method is crucial. In this work, WPC was composed by 60 wt% poly(butylene succinate) (PBS) matrix, 10 wt% compatibilizer, and 30 wt% wood flour (WF) through extruder and injection machine. The effects of PBS diol-based polyurethane prepolymer (PBSPUP) compatibilizer on the structure and properties of WPCs were investigated. Compared with the WF30P70 sample, the tensile strength and the elongation at break of WF30PU10P60 sample had an increase of 52.1% and 125.0%, respectively. And the equilibrium water absorption of WF30PU10P60 was reduced from 4.79% (WF30P70) to 3.57%, the flow properties of WF30PU10P60 were also improved at the same time. Apparently, the composites containing the poly(butylene succinate) diol-based polyurethane prepolymer (PBSPUP) compatibilizer exhibited improved mechanical properties and thermal performance as shown by the results of scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, water absorption, rheological property analyses, and so on. Toward this end, the special PBSPUP interface structure played an important role in improving the properties of the WPC.