This work developed a series of siloxane-modified polyurethane (PU–Si) containing ordered hard segments by a facile method. The polyaddition between poly(ε-caprolactone) and excess diurethane diisocyanate was carried out to synthesize a polyurethane prepolymer with terminal isocyanate groups, which was then end-capped by 3-aminopropyl triethoxysilane to produce alkoxysilane-terminated polyurethane; the target products of PU–Si were obtained with hydrolysis and the condensation of alkoxysilane groups. The chemical structures were confirmed by FT-IR and XPS, and the effect of the siloxane content or cross-linked degree on the physicochemical properties of the PU–Si films was investigated in detail. The formation of the network structure linked by Si–O–Si bonds and interchain denser hydrogen bonds endowed PU–Si films with fine phase compatibility, low crystallinity, high thermal stability, and excellent tensile properties. Due to the high cross-linked degree and low interfacial energy, the films displayed a high surface water contact angle and low equilibrium water absorption, which resulted in slow hydrolytic degradation rates. Furthermore, the evaluation of protein adsorption and platelet adhesion on the PU–Si film surface presented high resistance to biofouling, indicating superior surface biocompatibility. Consequently, the siloxane–cross-linked polyurethane, which possessed excellent tensile properties, high biostability, and superior biocompatibility, showed great potential to be explored as biomaterials for durable implants.